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1: Introduction and Background - Biology

1: Introduction and Background - Biology


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1: Introduction and Background

Umuc Biology 102/103 Lab 1: Introduction to Science

Abstract
From intellectuals to policy-makers alike. All of the extraordinary output on the subject of al-Qaeda, has recently led to a number of far-reaching theories about the group which remain startlingly unexplored. The two assumptions, this paper examines and reveals each one's foundational role in assertions as well as debates about al-Qaeda, despite the relatively unexplored status of each. These 2 assumptions relate to: (1) the role of the internet in actual terrorist activity and (2) the association between combating a global “Al-Qaeda and combating al-Qaeda in Iraq”.

Mueller's ever-burgeoning bookish literature which anyone familiar with terrorism would recognize, quickly titled the 'Six rather unusual propositions about terrorism'. Is what my research paper plays off. In 2005, Mueller's astute and incisive piece brought to the forefront six unfamiliar assumptions about terrorism that should already have spawned discussion among intellectuals in the field, but had not, until his work provocatively presented those propositions. In a similar stratum, this research paper focuses on 2 rather unfamiliar theories about al-Qaeda which I think demand far greater research, attention, and debate than Mueller's had received thus far. It is my intention to focus these reflections on some insufficiently explored theories regarding particularly al-Qaeda. However, most of the theories relate more broadly to terrorism concerning issues in general. What is meant here by the phrase ' moderately unfamiliar assumptions '? By ' unfamiliar ', this dialogue proposes that the thinking explored here prowl beneath many of the affirmations made by intellectuals on al-Qaeda. This coupled with getting beneath many of the affirmations frequently put forward by political types (politicians and policy-makers). Humbly, this is not to imply that these particular assumptions are shared universally: in fact, many of the theories are really opposing pairs of, dichotomous conjectures, with those partisan to one side of a certain debate embracing that conjecture while their opponents reciprocate the other. Centrally the point is that these outright and crucial foundational notions concerning al-Qaeda, are for many assertions made by those addressing key issues and debating in the field.

By ' assumptions ', these reflections suggest that Mueller's six assumptions have been given inadequate attention in terrorism scholarship and dialogue. Not saying that these assumptions have been converted into the bases for other claims because they have been considered so obviously true and were taken for granted, or so indispensable research as to be automatically accepted for any scholarship whatsoever to continue. Contrarily, these assumptions engross some complex, consequential matters. This being said too often they have been accepted and neglected in favor of important research in other directions. What I hope to achieve with this paper is to draw attention to them, and in doing so, persuade their investigation through due diligent research and in depth analyses. Far too often these assumptions have not been totally ignored, but they have been left moderately unexplored. In addition, they also have been taken as the basis for other claims and assertions. For this reason, this research paper investigates 2 of the six assumptions, in an attempt to reveal what is habitually taken for granted in many conversations about al-Qaeda. This coupled with the consequent penalty for assertions made about counterterrorism and terrorism. In addition, proposals for how each assumption could be explored more completely and systematically are offered. This research paper then concludes by making a note of social science, and that it may.


Writing an Introduction for a Scientific Paper

This section provides guidelines on how to construct a solid introduction to a scientific paper including background information, study question, biological rationale, hypothesis, and general approach. If the Introduction is done well, there should be no question in the reader’s mind why and on what basis you have posed a specific hypothesis.

Broad Question: based on an initial observation (e.g., “I see a lot of guppies close to the shore. Do guppies like living in shallow water?”). This observation of the natural world may inspire you to investigate background literature or your observation could be based on previous research by others or your own pilot study. Broad questions are not always included in your written text, but are essential for establishing the direction of your research.

Background Information: key issues, concepts, terminology, and definitions needed to understand the biological rationale for the experiment. It often includes a summary of findings from previous, relevant studies. Remember to cite references, be concise, and only include relevant information given your audience and your experimental design. Concisely summarized background information leads to the identification of specific scientific knowledge gaps that still exist. (e.g., “No studies to date have examined whether guppies do indeed spend more time in shallow water.”)

Testable Question: these questions are much more focused than the initial broad question, are specific to the knowledge gap identified, and can be addressed with data. (e.g., “Do guppies spend different amounts of time in water <1 meter deep as compared to their time in water that is >1 meter deep?”)

Biological Rationale: describes the purpose of your experiment distilling what is known and what is not known that defines the knowledge gap that you are addressing. The “BR” provides the logic for your hypothesis and experimental approach, describing the biological mechanism and assumptions that explain why your hypothesis should be true.

The biological rationale is based on your interpretation of the scientific literature, your personal observations, and the underlying assumptions you are making about how you think the system works. If you have written your biological rationale, your reader should see your hypothesis in your introduction section and say to themselves, “Of course, this hypothesis seems very logical based on the rationale presented.”

  • A thorough rationale defines your assumptions about the system that have not been revealed in scientific literature or from previous systematic observation. These assumptions drive the direction of your specific hypothesis or general predictions.
  • Defining the rationale is probably the most critical task for a writer, as it tells your reader why your research is biologically meaningful. It may help to think about the rationale as an answer to the questions—how is this investigation related to what we know, what assumptions am I making about what we don’t yet know, AND how will this experiment add to our knowledge? *There may or may not be broader implications for your study be careful not to overstate these (see note on social justifications below).
  • Expect to spend time and mental effort on this. You may have to do considerable digging into the scientific literature to define how your experiment fits into what is already known and why it is relevant to pursue.
  • Be open to the possibility that as you work with and think about your data, you may develop a deeper, more accurate understanding of the experimental system. You may find the original rationale needs to be revised to reflect your new, more sophisticated understanding.
  • As you progress through Biocore and upper level biology courses, your rationale should become more focused and matched with the level of studye., cellular, biochemical, or physiological mechanisms that underlie the rationale. Achieving this type of understanding takes effort, but it will lead to better communication of your science.

***Special note on avoiding social justifications: You should not overemphasize the relevance of your experiment and the possible connections to large-scale processes. Be realistic and logical—do not overgeneralize or state grand implications that are not sensible given the structure of your experimental system. Not all science is easily applied to improving the human condition. Performing an investigation just for the sake of adding to our scientific knowledge (“pure or basic science”) is just as important as applied science. In fact, basic science often provides the foundation for applied studies.

Hypothesis / Predictions: specific prediction(s) that you will test during your experiment. For manipulative experiments, the hypothesis should include the independent variable (what you manipulate), the dependent variable(s) (what you measure), the organism or system, the direction of your results, and comparison to be made.

Hypothesis that Needs Work

(manipulative experiment)

Better Hypothesis

(manipulative experiment)

We hypothesized that Daphnia magna reared in warm water will have a greater sexual mating response.

(The dependent variable “sexual response” has not been defined enough to be able to make this hypothesis testable or falsifiable. In addition, no comparison has been specified— greater sexual mating response as compared to what?)

We hypothesized that Daphnia magna (STUDY ORGANISM) reared in warm water temperatures ranging from 25-28 °C (IND. VAR.) would produce greater (direction) numbers of male offspring and females carrying haploid egg sacs (DEPEND. VAR.) than D. magna reared in cooler water temperatures of 18-22°C.

If you are doing a systematic observation, your hypothesis presents a variable or set of variables that you predict are important for helping you characterize the system as a whole, or predict differences between components/areas of the system that help you explain how the system functions or changes over time.

Hypothesis that Needs Work

(systematic observation)

Better Hypothesis

(systematic observation)

We hypothesize that the frequency and extent of algal blooms in Lake Mendota over the last 10 years causes fish kills and imposes a human health risk.

(The variables “frequency and extent of algal blooms,” “fish kills” and “human health risk” have not been defined enough to be able to make this hypothesis testable or falsifiable. How do you measure algal blooms? Although implied, hypothesis should express predicted direction of expected results [e.g., higher frequency associated with greater kills]. Note that cause and effect cannot be implied without a controlled, manipulative experiment.)

We hypothesize that increasing (DIRECTION) cell densities of algae (VAR.) in Lake Mendota over the last 10 years is correlated with 1. increased numbers of dead fish (VAR.) washed up on Madison beaches and 2. increased numbers of reported hospital/clinical visits (VAR.) following full-body exposure to lake water.


Experimental Approach
: Briefly gives the reader a general sense of the experiment, the type of data it will yield, and the kind of conclusions you expect to obtain from the data. Do not confuse the experimental approach with the experimental protocol. The experimental protocol consists of the detailed step-by-step procedures and techniques used during the experiment that are to be reported in the Methods and Materials section.

Some Final Tips on Writing an Introduction

  • As you progress through the Biocore sequence, for instance, from organismal level of Biocore 301/302 to the cellular level in Biocore 303/304, we expect the contents of your “Introduction” paragraphs to reflect the level of your coursework and previous writing experience. For example, in Biocore 304 (Cell Biology Lab) biological rationale should draw upon assumptions we are making about cellular and biochemical processes.
  • Be Concise yet Specific: Remember to be concise and only include relevant information given your audience and your experimental design. As you write, keep asking, “Is this necessary information or is this irrelevant detail?” For example, if you are writing a paper claiming that a certain compound is a competitive inhibitor to the enzyme alkaline phosphatase and acts by binding to the active site, you need to explain (briefly) Michaelis-Menton kinetics and the meaning and significance of Km and Vmax. This explanation is not necessary if you are reporting the dependence of enzyme activity on pH because you do not need to measure Km and Vmax to get an estimate of enzyme activity.
  • Another example: if you are writing a paper reporting an increase in Daphnia magna heart rate upon exposure to caffeine you need not describe the reproductive cycle of magna unless it is germane to your results and discussion. Be specific and concrete, especially when making introductory or summary statements.

Where Do You Discuss Pilot Studies?
Many times it is important to do pilot studies to help you get familiar with your experimental system or to improve your experimental design. If your pilot study influences your biological rationale or hypothesis, you need to describe it in your Introduction. If your pilot study simply informs the logistics or techniques, but does not influence your rationale, then the description of your pilot study belongs in the Materials and Methods section.

Introduction That Needs Work from an Intro Ecology Lab:

Researchers studying global warming predict an increase in average global temperature of 1.3°C in the next 10 years (Seetwo 2003). (background info) Daphnia magna are small zooplankton that live in freshwater inland lakes. They are filter-feeding crustaceans with a transparent exoskeleton that allows easy observation of heart rate and digestive function. Thomas et al (2001) found that Daphnia heart rate increases significantly in higher water temperatures. (background info., not relevant or necessary) Daphnia are also thought to switch their mode of reproduction from asexual to sexual in response to extreme temperatures. (unreferenced background info) Gender is not mediated by genetics, but by the environment. Therefore, D. magna reproduction may be sensitive to increased temperatures resulting from global warming (maybe a question?) and may serve as a good environmental indicator for global climate change. (The latter part of this last sentence is an overzealous social justification for the experiment.)

In this experiment we hypothesized that D. magna reared in warm water will switch from an asexual to a sexual mode of reproduction. (hypothesis) In order to prove this hypothesis correct we observed Daphnia grown in warm and cold water and counted the number of males observed after 10 days. (approach)

· Good to recognize D. magna as a model organism from which some general conclusions can be made about the quality of the environment however no attempt is made to connect increased lake temperatures and D. magna gender. Link early on to increase focus.

· Connection to global warming is too far-reaching. First sentence gives impression that Global Warming is topic for this paper. Changes associated with global warming are not well known and therefore little can be concluded about use of D. magna as indicator species.

· Information about heart rate is unnecessary because heart rate in not being tested in this experiment.

· Rationale is missing how is this study related to what we know about D. magna survivorship and reproduction as related to water temperature, and how will this experiment contribute to our knowledge of the system?

· Think about the ecosystem in which this organism lives and the context. Under what conditions would D. magna be in a body of water with elevated temperatures?

· Not falsifiable variables need to be better defined (state temperatures or range tested rather than “warm” or “cold”) and predict direction and magnitude of change in number of males after 10 days.

· It is unclear what comparison will be made or what the control is

· What dependent variable will be measured to determine “switch” in mode of reproduction (what criteria are definitive for switch?)

· Hypotheses cannot be “proven” correct. They are either supported or rejected.

Better Introduction
from an Intro Ecology Lab:

Daphnia magna are small zooplankton found in freshwater inland lakes and are thought to switch their mode of reproduction from asexual to sexual in response to extreme temperatures (Mitchell 1999). Lakes containing D. magna have an average summer surface temperature of 20°C (Harper 1995) but may increase by more than 15% when expose to warm water effluent from power plants, paper mills, and chemical industry (Baker et al. 2000). (background info) Could an increase in lake temperature caused by industrial thermal pollution affect the survivorship and reproduction of D. magna? (study question)

The sex of D. magna is mediated by the environment rather than genetics. Under optimal environmental conditions, D. magna populations consist of asexually reproducing females. When the environment shifts D. magna may be queued to reproduce sexually resulting in the production of male offspring and females carrying haploid eggs in sacs called ephippia (definition) (Mitchell 1999). (background info)

The purpose of this laboratory study is to examine the effects of increased water temperature on D. magna survivorship and reproduction. This study will help us characterize the magnitude of environmental change required to induce the onset of the sexual life cycle in D. magna. (biological rationale) Because D. magna are known to be a sensitive environmental indicator species (Baker et al. 2000) and share similar structural and physiological features with many aquatic species, they serve as a good model for examining the effects of increasing water temperature on reproduction in a variety of aquatic invertebrates. (biological rationale)

We hypothesized that D. magna (study organism) populations reared in water temperatures ranging from 24-26 °C (indep. Var) would have lower survivorship, higher [direction] male/female ratio among the offspring, and more female offspring carrying ephippia (depend. var) as compared with D. magna grown in water temperatures of 20-22°C. (hypothesis) To test this hypothesis we reared D. magna populations in tanks containing water at either 24 +/- 2°C or 20 +/- 2°C. Over 10 days, we monitored survivorship, determined the sex of the offspring, and counted the number of female offspring containing ephippia. (approach)

· Opening paragraph provides good focus immediately. The study organism, gender switching response, and temperature influence are mentioned in the first sentence. Although it does a good job documenting average lake water temperature and changes due to industrial run-off, it fails to make an argument that the 15% increase in lake temperature could be considered “extreme” temperature change.

· The study question is nicely embedded within relevant, well-cited background information. Alternatively, it could be stated as the first sentence in the introduction, or after all background information has been discussed before the hypothesis.

· Good. Well-defined purpose for study to examine the degree of environmental change necessary to induce the Daphnia sexual life
cycle.


How will introductions be evaluated?
The following is part of the rubric we will be using to evaluate your papers.


Introduction

When entering a gate of a magnificent city we can make a prediction about the splendor, pomposity, history, and civilization we will encounter in the city. Occasionally, gates do not give even a glimpse of the city, and it can mislead the visitors about inner sections of the city. Introduction sections of the articles are like gates of a city. It is a presentation aiming at introducing itself to the readers, and attracting their attention. Attractiveness, clarity, piquancy, and analytical capacity of the presentation will urge the reader to read the subsequent sections of the article. On the other hand as is understood from the motto of antique Greek poet Euripides 𠇊 bad beginning makes a bad ending”, ‘Introduction’ section of a scientific article is important in that it can reveal the conclusion of the article. [1]

It is useful to analyze the issues to be considered in the ‘Introduction’ section under 3 headings. Firstly, information should be provided about the general topic of the article in the light of the current literature which paves the way for the disclosure of the objective of the manuscript. Then the specific subject matter, and the issue to be focused on should be dealt with, the problem should be brought forth, and fundamental references related to the topic should be discussed. Finally, our recommendations for solution should be described, in other words our aim should be communicated. When these steps are followed in that order, the reader can track the problem, and its solution from his/her own perspective under the light of current literature. Otherwise, even a perfect study presented in a non-systematized, confused design will lose the chance of reading. Indeed inadequate information, inability to clarify the problem, and sometimes concealing the solution will keep the reader who has a desire to attain new information away from reading the manuscript. [1𠄳]

First of all, explanation of the topic in the light of the current literature should be made in clear, and precise terms as if the reader is completely ignorant of the subject. In this section, establishment of a warm rapport between the reader, and the manuscript is aimed. Since frantic plunging into the problem or the solution will push the reader into the dilemma of either screening the literature about the subject matter or refraining from reading the article. Updated, and robust information should be presented in the ‘Introduction’ section.

Then main topic of our manuscript, and the encountered problem should be analyzed in the light of the current literature following a short instance of brain exercise. At this point the problems should be reduced to one issue as far as possible. Of course, there might be more than one problem, however this new issue, and its solution should be the subject matter of another article. Problems should be expressed clearly. If targets are more numerous, and complex, solutions will be more than one, and confusing.

Finally, the last paragraphs of the ‘Introduction’ section should include the solution in which we will describe the information we generated, and related data. Our sentences which arouse curiosity in the readers should not be left unanswered. The reader who thinks to obtain the most effective information in no time while reading a scientific article should not be smothered with mysterious sentences, and word plays, and the readers should not be left alone to arrive at a conclusion by themselves. If we have contrary expectations, then we might write an article which won’t have any reader. A clearly expressed or recommended solutions to an explicitly revealed problem is also very important for the integrity of the ‘Introduction’ section. [1𠄵]

We can summarize our arguments with the following example ( Figure 1 ). The introduction section of the exemplary article is written in simple present tense which includes abbreviations, acronyms, and their explanations. Based on our statements above we can divide the introduction section into 3 parts. In the first paragraph, miniaturization, and evolvement of pediatric endourological instruments, and competitions among PNL, ESWL, and URS in the treatment of urinary system stone disease are described, in other words the background is prepared. In the second paragraph, a newly defined system which facilitates intrarenal access in PNL procedure has been described. Besides basic references related to the subject matter have been given, and their outcomes have been indicated. In other words, fundamental references concerning main subject have been discussed. In the last paragraph the aim of the researchers to investigate the outcomes, and safety of the application of this new method in the light of current information has been indicated.


Nutraceuticals: Introduction, Classification and Legal Aspects | Biology

In this article we will discuss about:- 1. Introduction to Nutraceuticals 2. Classification of Nutraceuticals 3. Current Status and Legal Aspects.

Introduction to Nutraceuticals:

Major scientific and engineering advances in recent decades have led to an increase in the development of expensive, high-technology medical and surgical procedures and drug therapies. At the same time, however, there has been an increase in the number of people turning to alternative medical therapies, which emphasize the importance of a ‘good diet’ in maintaining and restoring health.

The term “nutraceutical” was coined from “nutrition” and “pharmaceutical” in 1989, by Stephen DeFelice, MD, founder and chairman of the Foundation for Innovation in Medicine.

A nutraceutical can be defined as “any substance that may be considered a food or part of a food and provides medical or health benefits, including the prevention and treatment of disease. Such products may range from isolated nutrients, dietary supplements and diets to genetically engineered ‘designer’ foods, herbal products and processed foods such as cereals, soups and beverages.” Such foods are commonly referred to as functional foods, signifying that these foods and/or their components may provide a health benefit that goes beyond basic nutrition.

At present, there are no universally accepted definitions for nutraceuticals and functional foods, although commonality clearly exists between the definitions offered by different health-oriented professional organizations. According to the American Dietetic Association, the term “functional” implies that the food has some identified value leading to health benefits, including reduced risk of disease, for the person consuming it.

Functional foods include everything from natural foods, such as fruits and vegetables endowed with antioxidants and fibre, to fortified and enriched foods, such as orange juice with added calcium or additional carotenoids, to formulated ready-to-drink beverages containing antioxidants and immune-supporting factors. The Nutrition Business Journal states that it uses the term, nutraceutical, for anything that is consumed primarily or particularly for health reasons. Based on that definition, a functional food would be a kind of nutraceutical.

On the other hand, Health Canada states that a nutraceutical is a product that is “prepared from foods, but sold in the form of pills or powders (potions), or in other medicinal forms not usually associated with foods. A nutraceutical is demonstrated to have a physiological benefit or provide protection against chronic disease.”

Classification of Nutraceuticals:

Nutraceuticals can be classified on the basis of food source (Table 13.1), mechanism of action (Table 13.2), and chemical nature (Table 13.3).

Current Status and Legal Aspects of Nutraceuticals:

The nutraceutical industry has emerged as an important part of the food industry. With high economic growth, increasing income and changing lifestyles, the market is growing enormously. Globally, the nutraceutical market was placed at 65 billion dollars in 2002 and was expected to grow to 250 billion dollars by 2005. In India, this market is at about Rs. 1, 600 crore at present, with an annual growth rate of 25%.

In developed countries, predictable factors have been largely responsible for encouraging the growth of the nutraceutical industry. High disposable incomes, changing lifestyles with unhealthy eating habits, increasing incidence of health problems, an increasingly larger aging populations with unique dietary needs to maintain health, etc., have all prompted the development of new nutritional solutions, especially the use of nutraceuticals.

Therefore, there is a significant correlation between the growth of nutritional ingredients and demographic issues and confidence in the growth of nutraceutical products over the next 20 years.

Although this industry is also expanding in developing countries, it is difficult to predict its growth rate. Some of the reasons for this are – high population, disparity in levels of disposable income, spectrum of malnutrition including over- and under-nutrition etc. Notwithstanding the above, the Indian nutraceutical industry also has great prospects.

Over the last decade, a wide range of products have been available, giving an insight into the potential for tremendous growth. On the one hand, a booming economy has resulted in an overall increase in disposable incomes. Added to this, unhealthy eating habits coupled with a sedentary lifestyle have led to increased incidence of diet and related health issues.

On the other hand, there is growing awareness on the importance of nutrition and diet for long-term good health. These have contributed to favourable market conditions for the nutraceutical industry in India. Apart from this, India has other advantages like well-qualified and intelligent human resources for setting up R&D facilities of international standards.

The country is also a cost-effective source of sophisticated raw materials, due to technological advances in areas like fermentation processes, plant extraction and chemical synthesis. These converging economic and demographic trends in India have laid the groundwork for opportunities in the nutraceutical industry.

While prospects are high for this industry, India faces certain challenges too. The supply chain is a long one and is further affected by poor infrastructure in terms of roads, cold chain facilities and storage conditions. The wastage of fresh food is as high as 50% due to lack of infrastructure facilities.

Despite surplus food, the productivity of agricultural/horticultural crops is very low and the land-holding pattern is fragmented. In addition to this, the taxes levied on packaged and branded foods are very high – about 30% in India. In comparison, the taxes in EU countries are below 10% and even in other Asian countries like China, it is only 13%. All these disadvantages hinder India from gaining a competitive edge in the global market.

The regulatory framework in India also needs the attention of the relevant authorities. Globally, the regulatory authorities are aware of the changing needs of consumers and proactively protect consumers by amending existing laws to accommodate changes. NLEA (Nutrition Labelling and Education Act) of 1990 and DSHEA (Dietary Supplement and Health Education Act of 1994 are fine examples of this in the USA.

Similarly, the FOSHU Act (Foods of special Health Uses) was introduced in Japan much earlier. But the scenario in India is very different. Old laws such as the Prevention of Food Adulteration Act, 1954, which regulates packaged foods, still exist.

In addition, manufacturers need to abide by many other cumbersome laws [Fruit Products Order, 1955 (FPO) Vegetable Oils Products (Regulation) Order, 1998 (VOP) Agricultural Produce (Grading and Marking) Act, 1937 (as amended up to 1986) and General Grading and Marking Rules, 1986 and 1988 (AGMARK)].

In India, there is lack of clarity in classifying items into functional foods and nutraceuticals. This causes confusion among the regulators. At times, the drug regulators are tempted to classify these products as drugs. This has resulted in trouble for genuine manufacturers. Proper legislation is the need of the hour.

The Government of India has taken certain welcome steps like the amendment of the PFA (Prevention of Food Adulteration Act) which defines “Food for special dietary uses”. Another revolutionary step that is being planned is to introduce a Food Safety and Standards Act. This will replace the old PFA with new legislation. The new Act will take India on to the path of a new regulatory framework to make it capable of taking on global competition.


1: Introduction and Background - Biology

LITERATURE REVIEW PAPER

WHAT IS A REVIEW PAPER?

The purpose of a review paper is to succinctly review recent progress in a particular topic. Overall, the paper summarizes the current state of knowledge of the topic. It creates an understanding of the topic for the reader by discussing the findings presented in recent research papers.

A review paper is not a "term paper" or book report. It is not merely a report on some references you found. Instead, a review paper synthesizes the results from several primary literature papers to produce a coherent argument about a topic or focused description of a field.

Examples of scientific reviews can be found in:

  • Scientific American
  • Science in the "Perspectives" and "Reviews" sections
  • Nature in the "News and Views" section
  • Compilations of reviews such as:

Current Opinion in Cell Biology

Current Opinion in Genetics & Development

Annual Review of Plant Physiology and Plant Molecular Biology

Annual Review of Physiology

Trends in Ecology & Evolution


You should read articles from one or more of these sources to get examples of how your paper should be organized.

Scientists commonly use reviews to communicate with each other and the general public. There are a wide variety of review styles from ones aimed at a general audience (e.g., Scientific American) to those directed at biologists within a particular subdiscipline (e.g., Annual Review of Physiology).

A key aspect of a review paper is that it provides the evidence for a particular point of view in a field. Thus, a large focus of your paper should be a description of the data that support or refute that point of view. In addition, you should inform the reader of the experimental techniques that were used to generate the data.

The emphasis of a review paper is interpreting the primary literature on the subject. You need to read several original research articles on the same topic and make your own conclusions about the meanings of those papers.

Click here for advice on choosing a topic.

Click here for advice on doing research on your topic.

HOW TO WRITE THE PAPER

Overview of the Paper:

Your paper should consist of four general sections:

  • Introduction
  • The body of the paper
  • Conclusion and future directions
  • Literature cited

Review articles contain neither a materials and methods section nor an abstract.

Use topic headings. Do not use a topic heading that reads, "Body of the paper." Instead the topic headings should refer to the actual concepts or ideas covered in that section.

What Goes into Each Section:

  • Experimental Evidence: Describe important results from recent primary literature articles and
  • Explain how those results shape our current understanding of the topic.
  • Mention the types of experiments done and their corresponding data, but do not repeat the experimental procedure step for step. Examples
  • Point out and address any controversies in the field.
  • Use figures and/or tables to present your own synthesis of the original data or to show key data taken directly from the original papers.
  • Succinctly summarize your major points.
  • Point out the significance of these results.
  • Discuss the questions that remain in the area.
  • Keep it brief.
  • Your instructor will give you a minimum number of references that you must use and cite in your paper. Typically, at least 8-10 references are required.
  • Click here for how to handle citing sources.

Copyright © 2001, the University of Wisconsin-La Crosse and the Board of Regents of the University of Wisconsin.


1: Introduction and Background - Biology

Recorded: January 6, 2014

Lecture 1: Introduction

Course Description: This course is intended for both mathematics and biology undergrads with a basic mathematics background, and consists of an introduction to modeling biological problems using continuous ODE methods (rather than discrete methods as used in 113A). We describe the basic qualitative behavior of dynamical systems in the context of a simple population model and, as time allows, introduce other types of models such as chemical reactions inside the cell or excitable systems leading to oscillations and neuronal signals. Certain topics from linear algebra that are needed for this course are presented as well, so a linear algebra prerequisite is not necessary.

Required attribution: Enciso, German A. Math 113B (UCI Open: University of California, Irvine), http://open.uci.edu/courses/math_113b_intro_to_mathematical_modeling_in_biology.html. [Access date]. License: Creative Commons Attribution-ShareAlike 3.0 United States License.

Math 113B. Lec. 01. Intro to Mathematical Modeling in Biology: Introduction to the Course by German Andres Enciso Ruiz is licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License.


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SURVEY OF PLANTS USED IN BEAUTY CARE AMONG THE FULANIS IN WAMAKKO LOCAL GOVERNMENT AREA OF SOKOTO STATE

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AN INVESTIGATIVE STUDY ON THE VIEWS OF BIOLOGY STUDENTS ON THE PROBLEM OF LABORATORY MANAGEMENT AND SAFETY IN SECONDARY SCHOOLS

Item Type & Format: Project Material - Ms Word | 22 pages | Instant Download | Chapter 1-5 | BIOLOGY DEPARTMENT

MACROPHYTE DISTRIBUTION IN RELATION TO WATER QUALITY PARAMETERS IN SELECTED PONDS ALONG IKOT AKPADEM ACCESS ROAD, AKWA IBOM STATE

Item Type & Format: Project Material - Ms Word | 52 pages | Instant Download | Chapter 1-5 | BIOLOGY DEPARTMENT

EFFECT OF BIOLOGY PRACTICAL ON THE SECONDARY SCHOOL STUDENTS ACADEMIC PERFORMANCE IN BIOLOGY

Item Type & Format: Project Material - Ms Word | 61 pages | Instant Download | Chapter 1-5 | BIOLOGY DEPARTMENT

EPIDEMIOLOGICAL STUDIES AND MOLECULAR CHARACTERISATION OF DERMATOPHYTES AMONG ALMAJIRAI IN MAKARFI LOCAL GOVERNMENT AREA OF KADUNA STATE

Item Type & Format: Project Material - Ms Word | 81 pages | Instant Download | Chapter 1-5 | BIOLOGY DEPARTMENT

PRODUCTION OF LIQUID BIOFERTIZER AND BIOCHEMICAL CHARACTERISATION OF COMPONENT NITROGEN-FIXING AND PHOSPHATE-SOLUBILISING BACTERIA SPECIES

Item Type & Format: Project Material - Ms Word | 52 pages | Instant Download | Chapter 1-5 | BIOLOGY DEPARTMENT

IMPORTANCE OF IMPROVISTION IN TEACHING BIOLOGY TO SENIOR SECONDARY SCHOOL STUDENTS IN SOKOTO METROPOLIS

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EXAMINATION OF INCIDENCE OF MALARIA INFESTATION CAUSED BY DIFFERENT SPECIES OF PLASMODIUM

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ISOLATION AND IDENTIFICATION OF FUNGI SPOILAGE AND ORGANISMS IN PACKAGED AND UNPACKAGED MILK, SOYBEAN FLOUR AND CORN FLOUR

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THE EFFECTIVENESS OF INSTRUCTIONAL MATERIALS IN TEACHING AND LEARNING BIOLOGY IN SENIOR SECONDARY SCHOOL

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PHYTOCHEMICAL ANALYSIS OF CLEOME VISCOSA.

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EFFECT OF COOPERATIVE LEARNING STRATEGY ON ATTITUDE AND ACADEMIC PERFORMANCE OF BIOLOGY STUDENTS OF DIFFERENT COGNITIVE STYLES IN KADUNA STATE, NIGERI.

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COMPARE THE RATE OF GROWTH AND PLANT VIGOUR OF HYDROPONICALLY GROWTH PLANT TO PLANT GROWTH CONVENTIONAL ON SOIL

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THE PROBLEMS AND PROSPECT OF TEACHING BIOLOGY IN SECONDARY SCHOOLS (A CASE STUDY OF ENUGU SOUTH L.G.A)

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Imaging and Organelle Organization

Molecular Cell Biology: An Overview

Basic Molecular Components and Technology

Nucleic Acid Synthesis/Breakdown

Protein Synthesis and Degradation

Molecular Principles, Components, Technology, and Concepts

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: BASIC PRINCIPLES | Chemical and Physical Principles

The Laws of Thermodynamics and Living Cells

Gibbs Free Energy Always Decreases for a Spontaneous Process at Constant Temperature and Pressure

Gibbs Free Energy Changes are Additive

Coupling of ATP Hydrolysis to Drive Thermodynamically Unfavorable Reactions

Reaction Rate and Rate Constant

Reaction Rate-Limiting Step

Rate Constant and Activation Energy

Concerted and Sequential Models

Acid–Base Reactions Play a Central Role in Most Biochemical Processes

Noncovalent Interactions Play Key Roles in Mediating Functions of Biomacromolecules

Effect of Molecular Crowding in Living Cells

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: BASIC PRINCIPLES | Biocatalysis

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: NUCLEIC ACIDS | DNA, RNA Chemical Properties (Including Sequencing and Next-Generation Sequencing)

Physical Structure of Nucleic Acid

Chemical Modification of Nucleic Acids

DNA Modification by Radiation

Sequencing through DNA Synthesis

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: NUCLEIC ACIDS | The Chemical Synthesis of DNA and RNA Oligonucleotides for Drug Development and Synthetic Biology Applications

The Chemical Synthesis of Oligodeoxyribonucleotides

The Chemical Synthesis of Oligoribonucleotides via the Phosphoramidite Approach

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: PROTEINS | Expression Systems

Overview of Expression Systems

Bacterial Expression Systems

Cell-Free Expression Systems

Insect Expression Systems

Mammalian Expression Systems

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: PROTEINS | Isolation/Purification of Proteins

Migration in an Electric Field

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: PROTEINS | Protein Sequence Determination: Methodology and Evolutionary Implications

Sequencing Proteins by Chemical Techniques

Other Sequencing Methodology

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: PROTEINS | Posttranslational Modifications: Key Players in Health and Disease

Proteolytic PTM of Proteins

Glycosylation ( N - and O -linked)

Lipid Modification (Lipidation)

Oxidative Stress-Related PTMs

Ubiquitin and Targeted Protein Degradation

Conclusions: Many More PTMs Exist, and There Is Cross Talk between Them

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: PROTEINS | Protein Domains: Structure, Function, and Methods

Protein Structure: Motifs, Folds, and Domains

Identifying and Classifying Protein Domains

Domains in Evolution: Modularity and Combinatorial Protein Structure

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: PROTEINS | NMR in Structural and Cell Biology

Brief Historical Perspective of NMR and Solution Structure Determination of Macromolecules

Fundamentals of NMR Structure Determination

Place of NMR Spectroscopy in Structural and Cell Biology

Experimental and Computational Considerations

Structural Proteomics of the Bacterial Phosphotransferase System

Exploring Sparsely Populated States of Proteins and Their Complexes

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS | Proteins: Folding, Misfolding, Disordered Proteins, and Related Diseases

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: PROTEINS | Diseases of Protein Folding: Huntington’s Disease and Amyotrophic Lateral Sclerosis

Genetic Basis of HD and ALS

Effects of Protein Products on Protein Homeostasis

Clearance Pathways of Aggregates – Cellular UPS

Clearance Pathways of Aggregates – Autophagy Pathway

Cellular Transfer of Aggregates on Toxic Fragments

Cell Specificity and Susceptibility

Symptoms and Treatments of the Disease

Potential Treatments and Therapies

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: PROTEINS | Site-Directed Mutagenesis

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: PROTEINS | Chemical Biology

Chemical Biology and Drug Development

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: PROTEINS | Drug Design

History of Drug Development

Structural Biology and Drug Development

Drug Design and Biologics

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: PROTEINS | Antibodies and Improved Engineered Formats (as Reagents)

Antibodies for In Vitro Diagnosis, in Soluble (RIA), Surface-Bound (ELISA), Cell-Bound (Fluorescence-Activated Cell Sorting (FACS)), Tissue-Bound (IHC) and Modern E-Device Formats

Antibodies for In Vivo Applications: Immunotherapy with Humanization and Deimmunisation

Design of ‘Antibody Fragments’ for Unique Clinical Applications In Vivo

Pharmacokinetics of Intact Antibodies versus Fragments

Engineering Multiple Specificity in Antibody Fragments

Antibody Libraries: Construction, Display, and Selection

Production, Stability, and Expression Levels

High-Value Clinical Applications

Angiogenesis and Vascular Blockade/Transport

Image-Guided Surgery: From Radioactive Image-Guided Surgery (RIGS) to Fluorescence Image-Guided Surgery (FIGS)

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: LIPIDS | Lipidomics

Description of How the Components of the Lipidome Are Usually Analyzed

Lipidomics Databases and Other Online Tools

Examples of Findings Using Lipidomics Approaches

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: LIPIDS | Synthesis and Structure of Glycerolipids

Synthesis of Phosphatidic Acid

Synthesis of Phospholipids in Bacteria

Synthesis of Phospholipids in Eukaryotes

Roles of Phospholipids in Cell Function

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: LIPIDS | Cholesterol and Other Steroids

Cholesterol in Cell Membranes

Regulation of Cholesterol Biosynthesis

Cellular Cholesterol Homeostasis

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: LIPIDS | Glycolipids

Definition of ‘Glycolipid’ and Subcategories of Glycolipids

Glycosphingolipids – The Power of Combinatorial Biochemistry

Analysis of Glycolipids by ‘Omic’ Technologies

Perspective on the Future of Glycolipid Research

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: LIPIDS | Lipid Signaling

Lipid Classification and Nomenclature

The Primary Mammalian Signaling Lipids

Signaling Lipids are Spatially Restricted and Scarce

The Complexity of Lipid Signaling

Physiologic Roles of Signaling Lipids

Signaling Lipids and Disease

Recent Advances in Signaling Lipid Technologies

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: MEMBRANES | Composition, Physical Properties, and Curvature

General Traits of Biological Membranes

Mechanisms that Modifies the Bulk Lipid Composition of Organelles

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: MEMBRANES | Lipid Rafts/Membrane Rafts

The Physical States of Lipids in Lipid Bilayers

Formulation of the Lipid Raft Hypothesis

The Basis of Membrane Protein Interaction with Rafts

Detecting Rafts in Model Membranes

Detecting Rafts in Natural Membranes: Giant Plasma Membrane Vesicles

Using Detergents to Detect Rafts in Cells: Rationale and Limitations

Detecting Rafts in Cells: Microscopy and Spectroscopy

Detecting Rafts in Cells Using Sterol Modification

Biological Functions of Raft Domains in Cells

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: MEMBRANES | Membrane Potential: Concepts

Determinants of the Membrane Potential

Measuring Membrane Potential and Relative Membrane Permeability

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: MEMBRANES | The Outer Mitochondrial Membrane, a Smooth ‘Coat’ with Many Holes and Many Roles: Preparation, Protein Components, Interactions with Other Membranes, Involvement in Health, Disease, and as a Drug Target

Separation and Isolation of the Four Mitochondrial Compartments

Results: Protein/Enzyme Assignments of the Four Mitochondrial Compartments with an Emphasis on the Outer Mitochondrial Membrane

‘Moonlighting’ Roles of the Mitochondrial Outer Membrane with Its Intracellular Neighbors

Involvement of the Outer Mitochondrial Membrane in Major Diseases and Potential Drug Target

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: MEMBRANES | Neuronal Action Potentials and Ion Channel Allostery

Electrical Properties of Neurons

Anatomy of a Neuron and Flow of Information

Action Potential Propagation

Action Potential Invasion of the Nerve Terminal

Fate of Neurotransmitter in the Synaptic Cleft

Postsynaptic Receptors/Ligand-Gated Ion Channels

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: MEMBRANES | Cystic Fibrosis

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: CARBOHYDRATES | Glycogen and Starch

Structures of Glycogen and Starch

Genetic Modification of Starch and Glycogen Metabolism

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: CARBOHYDRATES | Proteoglycans

Structure and Synthesis of Proteoglycans

Cellular Functions of Proteoglycans in Health and Disease

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: CARBOHYDRATES | Hyaluronan

Structure and Cellular Metabolism

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: METABOLISM | Metabolic Regulation

Mechanisms for Regulation of Key Enzymes

Substrates (Fuel) Availability

Covalent Modification (or Posttranslational Modification)

Inhibitory Protein (Regulatory Protein) Interaction

Transcriptional and Degradational Control

Metabolism in the Fed State

Metabolism in the Fasted (Starvation) State

MOLECULAR PRINCIPLES, COMPONENTS, TECHNOLOGY, AND CONCEPTS: METABOLISM | A Structure Perspective on Organelle Bioenergetics

Energetics of Membrane-Based Adenosine Triphosphate Synthesis

Atomic Structures of Membrane Protein Complexes Responsible for Energization, That Is, Generation of the Δμ˜H+, of Mitochondria and Chloroplasts

Primary Charge Separation and Formation of a Membrane Potential Photosynthetic Reaction Centers

Nucleic Acid Synthesis/Breakdown

NUCLEIC ACID SYNTHESIS/BREAKDOWN: RNA SYNTHESIS/FUNCTION | Transfer RNA

Surprising Number of Roles of tRNAs beyond Translation

NUCLEIC ACID SYNTHESIS/BREAKDOWN: RNA SYNTHESIS/FUNCTION | Messenger RNA (mRNA): The Link between DNA and Protein

Prokaryotic mRNA Structure

NUCLEIC ACID SYNTHESIS/BREAKDOWN: RNA SYNTHESIS/FUNCTION | The Interplay between Eukaryotic mRNA Degradation and Translation

Overview of Eukaryotic mRNA turnover

mRNA Degradation is Intimately Linked to Translation

The Ying-Yang of Translational Initiation and Transcript Stability

Translation Elongation and mRNA Turnover

Translation Termination and mRNA Stability

Where Does Eukaryotic mRNA Degradation Occur Within the Cell?

The mRNA Cycle Hypothesis – From Polysome to p-Bodies (and Perhaps Back)

NUCLEIC ACID SYNTHESIS/BREAKDOWN: RNA SYNTHESIS/FUNCTION | miRNAs/Small Noncoding RNAs

Biogenesis of miRNAs in Animals

Mutations in the miRNA and the Pathway Genes Cause Human Diseases

NUCLEIC ACID SYNTHESIS/BREAKDOWN: RNA SYNTHESIS/FUNCTION | Small RNAs/Cancer

Introduction to Noncoding RNAs

Introduction to miRNAs: Discovery, Biogenesis, and Nomenclature

Other Forms of Noncoding RNAs and their Relevance to Cancer

NUCLEIC ACID SYNTHESIS/BREAKDOWN: RNA SYNTHESIS/FUNCTION | Riboswitches and Ribozymes

Evolutionary Importance of RNA

In Vitro Selection of Aptamers and Ribozymes

From Aptamers to Riboswitches

Control of Gene Expression by Riboswitches

Ribozymes are Ubiquitous in Nature

Ribozymes in the Replication of Viroids and Virusoids

Ribozymes as Mobile Genetic Elements

The Ribosome as a Ribozyme and Riboswitch

The glmS Ribozyme–Riboswitch

Ribozymes and Riboswitches as Cell Biological Tools

NUCLEIC ACID SYNTHESIS/BREAKDOWN: RNA SYNTHESIS/FUNCTION | Ribosomal RNAs and Protein Synthesis

Overview of Protein Synthesis

Functional Role of 16S and 23S rRNAs During Initiation

Functional Role of 16S and 23S RNAs During the Elongation Cycle

Functional Role of 16S and 23S RNAs During Termination

Functional Role of 16S and 23S RNAs During Recycling

Functional Role of 5S rRNA

NUCLEIC ACID SYNTHESIS/BREAKDOWN: RNA SYNTHESIS/FUNCTION | Comparison of Bacterial and Eukaryotic Replisome Components

Bacterial Replicative DNA Polymerases Are Distinct from Those of Eukaryotes

Sliding Clamps Are Conserved in All Cell Types

The Clamp Loader Was Also Present in LUCA

Bacterial and Eukaryotic Replicative Helicases

Primases Are Very Different in Bacteria Compared to Eukaryotes

Single-Strand DNA-Binding Protein

Comparison of Bacterial and Eukaryotic Replisomes

What Is Needed for the Future?

NUCLEIC ACID SYNTHESIS/BREAKDOWN: DNA SYNTHESIS/REPAIR | Telomeres and Telomerase

The End-Replication Problem

Telomeric Repeat-Containing RNA

Telomerase Reverse Transcriptase

Syndromes of Short Telomeres

Alternative Lengthening of Telomeres

NUCLEIC ACID SYNTHESIS/BREAKDOWN: DNA SYNTHESIS/REPAIR | Telomere Biology

Telomere Structure and Proteins

Telomere Replication and Length Maintenance

NUCLEIC ACID SYNTHESIS/BREAKDOWN: DNA SYNTHESIS/REPAIR | Eukaryotic Nucleotide Excision Repair

Assembly of the Incision Complex

Excision, Repair Synthesis, and Ligation

NUCLEIC ACID SYNTHESIS/BREAKDOWN: DNA SYNTHESIS/REPAIR | The Base Excision Repair Pathway

Maintenance of Genome Stability and the Role of Base Excision Repair

Basic Overview of the BER Pathway

DNA Base Damage Recognition and Removal by DNA Glycosylases

Abasic Site Incision and Processing of DNA Strand Break Ends

Insertion of the Correct Undamaged Nucleotide

The Long-Patch BER Pathway

The Importance of Key BER Proteins is Highlighted by Knockout Mouse Models

Regulation of BER Protein Levels

NUCLEIC ACID SYNTHESIS/BREAKDOWN: DNA SYNTHESIS/REPAIR | Nonhomologous DNA End Joining

Choice of DSB Repair Pathway

NUCLEIC ACID SYNTHESIS/BREAKDOWN: DNA SYNTHESIS/REPAIR | DNA Repair by Homologous Recombination

The Core Mechanism of Homologous Recombination

Recombination and Double-Strand Break Repair

Recombination and DNA Replication

Recombination and Interstrand Cross-Link Repair

Pathway Regulation and Crossover Control

NUCLEIC ACID SYNTHESIS/BREAKDOWN: TRANSCRIPTION | Prokaryotic Transcription

Bacterial RNA Polymerase Holoenzyme

The Process of Transcription in Bacteria

Mechanisms that Regulate Bacterial Transcription

Transcription and Regulation in Archaea

NUCLEIC ACID SYNTHESIS/BREAKDOWN: TRANSCRIPTION | Eukaryotic Transcriptional Regulation

RNA Polymerases I, II, and III

Promoters and Transcription Factors

Transcription Initiation and Elongation

NUCLEIC ACID SYNTHESIS/BREAKDOWN: TRANSCRIPTION | Distant Activation of Transcription by Enhancers

Bacterial Enhancer Action

Enhancer Action in Eukaryotes

NUCLEIC ACID SYNTHESIS/BREAKDOWN: TRANSCRIPTION | The Spliceosome and Pre-mRNA Splicing

The Chemistry of Splicing and the Architecture of the Intron

The Spliceosome is Composed of snRNAs and Proteins

Spliceosomes are Assembled from snRNPs on Introns

The Active Site of the Spliceosome

DExD/H Box Proteins are Essential Cofactors of the Spliceosome

Alternative Splicing Creates Multiple Products from a Single Gene

Splicing is Coupled to Other Cellular Processes

Defects in Splicing Cause Disease

NUCLEIC ACID SYNTHESIS/BREAKDOWN: TRANSCRIPTION | Pre-mRNA Splicing: Function and Dysfunction

Diseases of the Spliceosome: Dysfunction Sheds Light on Function

NUCLEIC ACID SYNTHESIS/BREAKDOWN: NUCLEIC ACID TECHNOLOGY | Transgenesis and Gene Replacement

Temporal Regulation of Transgenes

NUCLEIC ACID SYNTHESIS/BREAKDOWN: NUCLEIC ACID TECHNOLOGY | Viral Nucleic Acids

Group IV: (+) Strand RNA Viruses

Group V: (–) Strand RNA Viruses

Group VI: (+) Strand RNA Viruses with DNA Intermediates

Group VII: dsDNA Viruses with RNA Intermediates

Gene Expression Strategies of RNA Viruses

PROTEIN SYNTHESIS/DEGRADATION: TRANSLATION | Components, Initiation, Elongation, Termination, and Regulation

Components of Protein Synthesis

Eukaryotic Translation Factors

Termination of Translation and Ribosome Recycling

PROTEIN SYNTHESIS/DEGRADATION: TRANSLATION | Biogenesis of Secretory Proteins

Nascent Polypeptides Are Specifically Recognized and Delivered to the ER Membrane in a Co- or Posttranslational Manner

Conducting Channels Made of Integrated Membrane Proteins Translocate Nascent Polypeptides across the ER Membrane

The Nascent Polypeptides Form Their Native Structures in the ER Lumen with the Help of Multiple Factors

A Comprehensive Quality Control System in the ER Lumen Ensures that Only Correctly Folded/Assembled Proteins Are Transported with the Misfolded/Misassembled Ones to be Degraded

The Malfunctioning of Protein Folding in ER Are Known to Cause Folding Diseases

PROTEIN SYNTHESIS/DEGRADATION: TRANSLATION | The Protein Biosynthetic Machinery of Mitochondria

Information Content of Mitochondrial DNA

Components of the Translational System

Mechanism of Mitochondrial Protein Biosynthesis

PROTEIN SYNTHESIS/DEGRADATION: TRANSLATION | Regulated Proteolysis of Signaling Molecules: The Proprotein Convertases

Introduction to Regulated Proteolysis

The Proprotein Convertases

Prohormone Convertase 1/3 ( PCSK1 )

Prohormone Convertase 2 ( PCSK2 )

Proprotein Convertase 4 ( PCSK4 )

Paired Basic Amino Acid Cleaving Enzyme 4 (PACE4 PCSK6 )

Proprotein Convertase 5/6 ( PCSK5 )

Proprotein Convertase 7 ( PCSK7 )

Protein Degradation – General

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – GENERAL | Mass Spectrometry-based Methodologies for Studying Proteolytic Networks and the Degradome

Validation of Degradomic Data

Protein Degradation – Intracellular

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – INTRACELLULAR | Ubiquitin, Ubiquitin-Like Proteins, and Proteasome-Mediated Degradation

Ubiquitin and Ubiquitin-like Proteins

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – INTRACELLULAR | Endoplasmic Reticulum-Associated Degradation and Protein Quality Control

The Manufacturing of a Secretory Protein

Unforgivable Errors: The ERADication of an Unfolded Protein

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – INTRACELLULAR | Role of Lysosomes in Intracellular Degradation

Protein Degradation – Protease Classes

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PROTEASE CLASSES | Matrix Metalloproteinases

Substrate Profiles: Biological and Biomedical Implications

Cellular Regulation of MMPs

MMPs as Therapeutic Targets and Anti-Targets: The Use of Synthetic Inhibitors

MMP Activity in Drug Delivery Mechanisms

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PROTEASE CLASSES | ADAMTS Proteases: Mediators of Physiological and Pathogenic Extracellular Proteolysis

Introduction, Defining Characteristics and Phylogeny of A Disintegrin-Like and Metalloprotease Domain with Thrombospondin Type 1 Motif Proteinases

Domain Organization and 3-Dimensional Structure

Biosynthesis and Regulation

Mechanistic Basis of Genetic and Acquired Disorders Involving ADAMTS Proteases

Functions in Mammalian Development Gleaned from Mouse Mutants

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PROTEASE CLASSES | ADAMs Regulate Cell–Cell Interactions by Controlling the Function of the EGF-Receptor, TNF α and Notch

ADAM17, the TNFα Convertase

ADAM17 is Crucial for EGFR Signaling

ADAM17-Dependent EGFR Activation Protects the Skin and Intestinal Barrier

ADAM17/TNFα and ADAM17/EGFR Signaling are Controlled by Upstream Regulators Called iRhoms

ADAM10, A Crucial Regulator of Notch Signaling

Other Substrates of ADAM10 and ADAM17

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PROTEASE CLASSES | Extracellular: Plasma Membrane Proteases – Serine Proteases

Membrane-Anchored Serine Proteases

The GPI-Anchored Serine Proteases

The Type I Transmembrane Serine Proteases

The Type II Transmembrane Serine Proteases

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PROTEASE CLASSES | Aspartic Proteases of Alzheimer’s Disease: β- and γ-Secretases

Amyloid and Alzheimer’s Disease

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PROTEASE CLASSES | The Calpain Proteolytic System

Structure of Conventional Calpains

Classification of Calpains

Regulation and Activation of Calpains

Physiological Functions of Calpains and the Role of Dysregulation in Human Disease

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PROTEASE CLASSES | Cathepsin E: An Aspartic Protease with Diverse Functions and Biomedical Implications

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PROTEASE CLASSES | Metalloproteases Meprin α and Meprin β in Health and Disease

Structural Features of Meprin α and Meprin β

Inhibition of Meprin Metalloproteases

Cleavage Specificity and Identification of Substrates by Proteomics

Physiologic and Pathologic Role of Meprin α and Meprin β

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PROTEASE CLASSES | Kallikrein

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PROTEASE CLASSES | Naturally-Occurring Polypeptide Inhibitors: Cystatins/Stefins, Inhibitors of Apoptosis (IAPs), Serpins, and Tissue Inhibitors of Metalloproteinases (TIMPs)

Tissue Inhibitors of Metalloproteinases

PROTEIN SYNTHESIS/DEGRADATION: PROTEOLYTIC PATHWAYS | Overview of Blood Coagulation and the Pathophysiology of Blood Coagulation Disorders

Overview of Blood Coagulation

Regulation of Blood Coagulation

Coagulation Disorders Overview

PROTEIN SYNTHESIS/DEGRADATION: PROTEOLYTIC PATHWAYS | Molecular Mechanisms Underlying the Actions of the Complement System

Regulation of Complement Activation by Proteases and Binding Factors

PROTEIN SYNTHESIS/DEGRADATION: PROTEOLYTIC PATHWAYS | Digestive Proteases: Roles in the Human Alimentary Tract

Role of the Oral Cavity in Proteolysis

Role of the Stomach in Proteolysis

Role of the Small Intestine in Proteolysis

Role of the Large Intestine in Proteolysis

Protein Degradation – Pathological Aspects

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PATHOLOGICAL ASPECTS | Inhibitors of HIV Protease

Structure and Enzymatic Mechanism of HIV Protease

Inhibitors of Retroviral Proteases

First generation of HIV-1 PR Inhibitors Approved as AIDS Drugs

Emergence of Resistance to Clinical Inhibitors of HIV-1 PR

Roads Not Taken – Inhibitors of HIV-1 PR That Did Not Become Drugs

Where Will the HIV-1 PR Inhibitors Be in the Future?

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PATHOLOGICAL ASPECTS | Blood Pressure, Proteases and Inhibitors

Proteolytic Regulation of Blood Pressure

The Natriuretic Peptide Family and Their Proteases (Corin, Furin, and NEP)

The Endothelin Peptide Family and Their Proteases

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PATHOLOGICAL ASPECTS | Cancer – Proteases in the Progression and Metastasis

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PATHOLOGICAL ASPECTS | Lysosomal Diseases

Related Conditions Affecting Organelle Biogenesis

Functional Complementation of Lysosomal Diseases

Treatment of Lysosomal Diseases

Therapeutic Stratagems for Lysosomal Diseases with Neurological Manifestations

Pathogenesis and Physiological Understanding

PROTEIN SYNTHESIS/DEGRADATION: PROTEIN DEGRADATION – PATHOLOGICAL ASPECTS | Alpha-1-Antitrypsin Deficiency: A Misfolded Secretory Glycoprotein Damages the Liver by Proteotoxicity and Its Reduced Secretion Predisposes to Emphysematous Lung Disease Because of Protease-Inhibitor Imbalance

Physiology and Function of AT

Mechanism of Deficiency in the Classical form of ATD

Cellular Mechanisms of Liver Disease

Cellular Mechanisms of Lung Disease

Cellular Responses to Misfolding of Mutant ATZ

Therapies for ATD Liver Disease

Therapies for ATD Lung Disease

Organizational Cell Biology

Organizational Cell Biology: An Overview

IMAGING THE CELL: ELECTRON MICROSCOPY | Single-Particle CryoEM of Macromolecular Complexes

CryoEM Sample Consideration

Frozen, Hydrated Specimen Preparation

Resolution of CryoEM Density Maps

CryoEM Model Building and Model Validation

High-Resolution CryoEM Structures

Identifying Different Populations Within a Heterogeneous Sample

Delineating the Conformational Changes of a Molecular Machine

IMAGING THE CELL: ELECTRON MICROSCOPY | Scanning Electron Microscopy in Cell Biology

Scanning Electron Microscopy ‘Versus’ Transmission Electron Microscopy

Beam – Specimen Interactions

Specimen Preparation for SEM

Serial Block Face Imaging

SEM and the Nuclear Envelope

IMAGING THE CELL: ELECTRON MICROSCOPY | Electron Tomography

Specimen Preparation Methods

Techniques to Combine with Cryo-ET

IMAGING THE CELL: ELECTRON MICROSCOPY | Immunoelectron Microscopy: High-Resolution Immunocytochemistry

Sample Preparation Strategies

Immunogold Label Quantification and Labeling Specificity

IMAGING THE IMAGING THE CELL: ELECTRON MICROSCOPY | Imaging Cellular Architecture with 3D SEM

Sample Preparation for 3D SEM

Orientation and Location of Region of Interest

Data Handling and Segmentation

New Methods and Future Developments

IMAGING THE CELL: LIGHT MICROSCOPY | Genetically Encoded Fluorescent Probes and Live Cell Imaging

Introduction – Fluorescent Proteins

Fluorescent Proteins as Probes for Function

Imaging Cells in Whole Organisms

Breaking the Diffraction Barrier

Technical Considerations for Live Imaging

IMAGING THE CELL: LIGHT MICROSCOPY | Total Internal Reflection Fluorescence Microscopy

Applications and Combinations in Cell Biology

Optical Configurations and Setup

TIRF versus Other Optical Sectioning Microscopies

IMAGING THE CELL: LIGHT MICROSCOPY | Super Resolution Fluorescence Localization Microscopy

IMAGING THE CELL: LIGHT MICROSCOPY | Super-Resolution Light Microscopy: Stimulated Emission Depletion and Ground-State Depletion

STED and GSD for Super-Resolution: Principle and Technology

Biological Applications of STED and GSDIM

IMAGING THE CELL: LIGHT MICROSCOPY | Structured Illumination Microscopy

Microscope Hardware, Software, and Data Acquisition

Imaging Artifacts: Causes and Manifestations

IMAGING THE CELL: LIGHT MICROSCOPY | Fluorescence Correlation Spectroscopy: A Tool for Measuring Dynamic and Equilibrium Properties of Molecules in Cells

Basic Concepts and Theory

Measurement of Molecular Association and Aggregation

IMAGING THE CELL: LIGHT MICROSCOPY | Fluorescence Lifetime Imaging – Applications and Instrumental Principles

FLIM Applications in Life Sciences

Clinical FLIM Applications

Technical Aspects of FLIM

IMAGING THE CELL: LIGHT MICROSCOPY | High-Speed Localization Microscopy and Single-Particle Tracking

IMAGING THE CELL: LIGHT MICROSCOPY | Intravital Microscopy in Mammalian Organisms: From Tissue Physiology to Cell Biology

Brief Historical Background on Intravital Microscopy

Imaging Techniques Used to Perform IVM

Current Applications of IVM

IMAGING THE CELL: LIGHT MICROSCOPY | Optogenetics

Light As a Tool in Biology

Optogenetics – Manipulating Molecules, Cells, and Organisms with Light

Light-Sensitive Proteins to Control Cellular Excitability

Optochemical Approaches to Control Specific Receptors and Ion Channels

Summary – From Molecules to Systems

ORGANELLES: STRUCTURE AND FUNCTION | The Endoplasmic Reticulum

Origin and Function of the ER

Membrane Contact Sites of the ER with Other Organelles

Translocation and Membrane Embedding of ER Client Proteins

Posttranslational Modifications of ER Client Proteins

Protein Folding in the ER

Export from and Retrieval to the ER

ORGANELLES: STRUCTURE AND FUNCTION | Intermediate Compartment: A Sorting Station between the Endoplasmic Reticulum and the Golgi Apparatus

Structure, Distribution, and Dynamics

ORGANELLES: STRUCTURE AND FUNCTION | Golgi and TGN

The Golgi Apparatus – An Introduction

The Structure of the Golgi Apparatus

Transport through the Golgi

Molecular Mechanism of Transport

Glycosylation at the Golgi

Regulation of the Golgi Apparatus Structure and Function

Evolution of the Golgi Apparatus

ORGANELLES: STRUCTURE AND FUNCTION | Early Endosomal Compartments

Endosome Heterogeneity Reflects Functional Compartmentalization

Epithelial Cells Have Spatially Separated, Connected Endosomal Circuits

(Ultra)structure and Specialization

Regulation of Endosome Traffic

Early Endosome Maturation and Conversion to Late Endosomes

Retrieval of Proteins from Endosomes to the Trans Golgi Network

Recycling from Early Endosomes to the Plasma Membrane

Conclusion and Perspectives

ORGANELLES: STRUCTURE AND FUNCTION | The Late Endosome

The Early/Recycling Endosome Network

Biogenesis of the Multivesicular Body

The Late Endosome–Lysosome Network

Endosomes in Plants and Fungi

Lysosome Enzymes and Lysosomal Membrane Proteins

Composition and Fate of Intralumenal Membranes

Other Destinations: All Roads Do Not Lead to the Lysosomes

The Late Endosome: A Signaling Platform

ORGANELLES: STRUCTURE AND FUNCTION | Signaling from Endosomes

Different Cell Types Employ Signaling Endosomes for Distinct Purposes

Endocytic Routes Specify Signaling Outcome

Endocytosis Regulates Signal Termination and Cellular Response to Ligand Gradient

Endosomes – A World of Their Own

Endocytosis Regulates Spatial Signaling and Signal Amplification

Signaling Regulates Endocytosis

Endocytosis and Implications in Cancer

Conclusions and Future Perspectives

ORGANELLES: STRUCTURE AND FUNCTION | Conventional and Secretory Lysosomes

Cell Type-Specific Secretory Lysosomes

Biogenesis of Lysosomes and Secretory Lysosomes

Exocytosis of Secretory Lysosomes

Genetic Diseases Associate with Defects in Conventional or Secretory Lysosomes

ORGANELLES: STRUCTURE AND FUNCTION | Lysosome-Related Organelles

Morphology, Composition, and Function of Lysosome-Related Organelles

Biogenesis and Transport of LROs

Genetic Diseases Associated with Defects in LRO Biogenesis and Transport

ORGANELLES: STRUCTURE AND FUNCTION | At the Center of Autophagy: Autophagosomes

Macroautophagy and Autophagosomes

ORGANELLES: STRUCTURE AND FUNCTION | Peroxisomes

Introduction and Morphology

Some Important, Specialized Physiological Functions of Peroxisomes

Conserved Biochemical Pathways Present in Most Peroxisomes

Other Peroxisome Functions

Metabolic Cooperation and Interaction with Other Organelles

Peroxisome Abundance, Adaptability, and Regulation

Peroxisome Division, Transport, and Inheritance

Remodeling, Random Turnover, and Selective Degradation

Human Disease and Peroxisomes

ORGANELLES: STRUCTURE AND FUNCTION | Lipid Droplets

Neutral Lipid Synthesis and Lipolysis

Lipid Droplets and Disease

ORGANELLES: STRUCTURE AND FUNCTION | Mechanisms and Functions of Mitochondrial Dynamics

Mitochondrial Fusion Machinery and Regulation

Molecular Insights into Drp1 Actions During Mitochondrial Fission

Physiologic Importance of Mitochondrial Dynamics

ORGANELLES: STRUCTURE AND FUNCTION | Synaptosomes and Synaptic Vesicles

Organelles: Structure and Function | Extracellular Vesicles

The Physiological Role of EVs: From Waste Bin to Versatile Transporter of Biological Signals

EVs in Cross-Kingdom Communication

Clinical Applications of EVs

ORGANELLES: STRUCTURE AND FUNCTION | Nuclear Organization (Nuclear Structure and Dynamics)

Nuclear Structure and Function

ORGANELLES: STRUCTURE AND FUNCTION | Nuclear Pores

Structure of the Nuclear Pore Complex

Dynamic Behavior of Nuceloporin

ORGANELLES: STRUCTURE AND FUNCTION | Plastids: The Anabolic Factories of Plant Cells

Plastids of the Viridiplantae

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | ER–Golgi Transport

Cargo Capture during Vesicle Formation

Regulation of COPII Biogenesis: The GTPase Cycle

Cellular Regulation of COPII Vesicle Biogenesis

Regulation of Vesicle Size

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | N-Linked Glycans (N-Glycans)

Initiation of an N-Glycan on Dolichol-Phosphate

Maturation of the Dol-P-P-Oligosaccharide

En-Bloc Transfer of an N-Glycan to Protein

Processing and Folding of Glycoproteins in the ER

Unique Modification of Lysosomal Hydrolases

Maturation of N-Glycans During Transit Through Golgi Compartments

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Extracellular O-Glycans

Mucin-Type O-Glycans/O-GalNAc Glycans

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Intra-Golgi Transport

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Post-Golgi Transport – Cargo, Carriers, and Pathways

Cargo Sorting and Packaging at the TGN

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Regulation of the Secretory Pathway

Constitutive and Regulated Secretion

The Regulation of Constitutive Secretion

Extent of the Regulation Network of the Secretory Pathway

Traffic Regulation in Response to Environmental Signals and Demands

Signaling Pathways that Support Homeostasis and Coordination of the Secretory Apparatus with Other Cellular Modules

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Regulated versus Constitutive Secretion – A Major Form of Intercellular Communication

How Do We Know about Regulated versus Constitutive Secretion?

Tour of Regulated Secretion

The Steps of Regulated Exocytosis

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Clathrin and Clathrin-Dependent Endocytosis

Cellular Function and Regulation of Clathrin

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Clathrin Independent Endocytosis

Clathrin- and Caveolin-Independent Micropinocytic Pathways

Conclusions and Perspectives

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Rabs of the Endosomal Recycling Pathway

Rab4 and the ‘Short-Loop’ Recycling Pathway

Rab11 and the Endosomal Recycling Compartment

Other Rabs of the Endosomal Recycling Pathway

Intracellular Pathogens Subvert the Function of Rab GTPases

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Endosome to Lysosome Transport

Endocytic Vesicles and Early Endosomes

Biogenesis of MVBs and Cargo Sorting

Role of pH and Ion Concentrations in Endosomal Maturation

Perinuclear Clustering of LE and Fusion Events

Role of Cytoskeletal Elements and of Molecular Motors

Conclusions and Perspectives

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Endocytosis of Cargo Proteins: LDL

Low Density Lipoprotein Biosynthesis

Cargo-Selective Clathrin Adaptors for the LDL Receptor

Dynamic Modulation of LDL Receptor Surface Levels

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Retrograde Transport

Different Retrograde Pathways

Biophysical Mechanisms for Retrograde Trafficking

Biomedical Applications of Retrograde Trafficking

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Rabs and Other G Proteins

Rab Family of G Proteins and Membrane Trafficking

Biosynthesis and Membrane Targeting of Rab Proteins

Structure and GTPase cycle of Rab Proteins

Effectors and Functions of Rab Proteins

INTERORGANELLAR COMMUNICATION: COMPONENTS | Adaptor Proteins: Inter-Organelle Traffic Controllers

Heterotetrameric Adaptor Complexes

The Epsin and Eps15 Families

AP180 and Clathrin Assembly Lymphoid Myeloid Leukemia

PTB Domain Containing Family (DAB, ARH, and Numb)

The Adaptor Protein Network

INTERORGANELLAR COMMUNICATION: COMPONENTS | SNAREs: Membrane Fusion and Beyond

Introduction: A Brief Historical Perspective on Soluble N -Ethylmaleimide-Sensitive Factor Attachment Protein Receptors (SNAREs)

SNAREs: Membrane Fusion Nanomachines

The Regulators of the SNARE Nanomachine

SNAREs: More than Fusogenic Proteins? The Case of the Longin v-SNAREs Sec22b and TI-VAMP/VAMP7

INTERORGANELLAR COMMUNICATION: COMPONENTS | ESCRTing around the Cell

ESCRTs in the Endolysosomal System

ESCRTs in Extracellular Vesicle Biogenesis

Non-Endosomal Roles for the ESCRT Machinery

INTERORGANELLAR COMMUNICATION: COMPONENTS | The Retromer Complex

A Brief History of Retromer

The Assembly and Structure of Retromer

How Membrane Tubules are Stabilized

Accessory Proteins that Modulate Retromer Function

The Physiological Processes That Depend on Retromer

INTERORGANELLAR COMMUNICATION: COMPONENTS | Vesicle Tethers

Interactions with Small GTPases and SNARE Proteins

Multisubunit Tethering Complexes

INTERORGANELLAR COMMUNICATION: COMPONENTS | BAR Domains and BAR Domain Superfamily Proteins

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Role of Phosphoinositides in Membrane Traffic

Phosphoinositides at the Membrane–Cytosol Interface

Organelle Compartments the Spatial Restriction of Phosphoinositide Species and Organelle Identity

Phosphoinositides in Plasma Membrane Trafficking

Phosphoinositides in the Endosomal Compartment – Early Endosomes, Recycling Endosomes, and Late Endosomes

Phosphoinositides in Golgi Trafficking

Retrograde Trafficking from Endosomes to Golgi

Phosphoinositides in the Regulation of Autophagy

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Unconventional Protein Secretion: Fibroblast Growth Factor 2 and Interleukin-1β as Examples

Mechanisms of Eukaryotic Protein Secretion

Hallmarks of FGF2 Membrane Translocation during Unconventional Secretion

The Molecular Mechanism of FGF2 Membrane Translocation and Its Path of Discovery

PI(4,5)P2-Induced FGF2 Oligomerization and Membrane Pore Formation: A Transient Intermediate in FGF2 Membrane Translocation

Understanding the Regulation of IL-1β Processing

IL-1β Secretion and Cell Death

Mechanisms of IL-1β Release

Unconventional Secretion – What Is It Good for?

INTERORGANELLAR COMMUNICATION: INTERPLAY AND PROCESSES | Endoplasmic Reticulum Stress in Disease

The Role of the UPR in Human Health and Disease

CYTOSKELETON AND MOTORS: CYTOSKELETAL COMPONENTS | Microtubules and Microtubule-Associated Proteins (MAPs)

Cellular Functions of Microtubules

Regulation of Microtubule Structure and Mechanics by MAPs

Regulation of Microtubule Dynamics by MAPs

Arrangement of Microtubules into Higher-Order Structures by MAPs

Microtubules in Human Disease

CYTOSKELETON AND MOTORS: CYTOSKELETAL COMPONENTS | Actin Assembly Dynamics and Its Regulation in Motile and Morphogenetic Processes

Actin: Structural and Mechanical Properties

Actin Self-Assembly: Nucleation-Growth, Thermodynamics, Polarity, ATP Hydrolysis

Regulation of Actin Assembly by Associated Proteins

Site-directed Branching of Actin Filaments by WASP Protein Family and Arp2/3 Complex

Integrated Protein Modules in Reconstituted Actin-Based Motility

Actin Regulators in Adhesion Structures

Actin-Based Molecular Motors: The Family of Myosins

Actin in the Nucleus? Potential Role of Actin in the Regulation of Gene Expression

Bacterial Actin Ancestors

CYTOSKELETON AND MOTORS: CYTOSKELETAL COMPONENTS | Intermediate Filaments

The Intermediate Filament Protein Family is Subdivided into Six Types with Cell Type-Specific Expression Patterns

Intermediate Filament Proteins Are Reliable Markers of Cellular Differentiation

Intermediate Filaments Share a Common Secondary Structure

Intermediate Filaments Can Be Assigned to Three Different Assembly Groups

Intermediate Filament Networks Have Distinct Properties That Render Them Different from the Other Cytoskeletal Systems

Cytoplasmic Intermediate Filament Network Organization Is Determined by Interaction with Major Cellular Components through Associated Proteins

Lamin Intermediate Filaments Contribute to Nuclear Structure and Function

Intermediate Filament Proteins Are Posttranslationally Modified

Intermediate Filaments Serve Many Functions

Cytoplasmic Intermediate Filament Dysfunctions Cause Tissue-Specific Diseases

Lamin Intermediate Filament Mutations Cause Complex Syndromes

Highly Diverse Intermediate Filament Proteins Occur Throughout the Animal Kingdom

CYTOSKELETON AND MOTORS: CYTOSKELETAL COMPONENTS | Septins: Cytoskeletal Filaments with Structural and Regulatory Functions

Septin Structure, Assembly, and Dynamics

Septins and the Membrane Skeleton

Septins and the Actin Cytoskeleton

Septins and the Microtubule Cytoskeleton

CYTOSKELETON AND MOTORS: CYTOSKELETAL COMPONENTS | Bacterial and Archaeal Cytoskeletons

Organization of Intracellular Membrane Compartments

CYTOSKELETON AND MOTORS: CYTOSKELETAL COMPONENTS | Myosins

Myosin Structure and Organization

Mechanochemical ATPase Cycle

Class-14 Myosins and -21 Myosins

CYTOSKELETON AND MOTORS: CYTOSKELETAL COMPONENTS | Kinesin Superfamily Proteins (KIFs) as a Fundamental Component of Life: Intracellular Transport and Beyond

Molecular Phylogeny and Nomenclature of Kinesins

Motor–Cargo Relationship and Pathophysiological Relevance

Regulation and Synergy of Kinesins

CYTOSKELETON AND MOTORS: CYTOSKELETAL COMPONENTS | Dyneins

Regulation of Dynein Motility

Functions of Cytoplasmic Dynein In Vivo

Axonemal Dyneins: Overall Arrangement and Structure

Function of Axonemal Dynein HCs in Cilia

Axonemal Dynein-Related Ciliopathies

Complex Cytoskeletal Structures

CYTOSKELETON AND MOTORS: COMPLEX CYTOSKELETAL STRUCTURES | The Mitotic Spindle

Architecture and Dynamics of the Mitotic Spindle

Different Paths of Spindle Assembly

The Role of Motors and MAPs in Mitotic Spindle Assembly

Mitotic Spindle Properties

Spindle Disassembly and Cytokinesis

CYTOSKELETON AND MOTORS: COMPLEX CYTOSKELETAL STRUCTURES | Centrioles and the Centrosome

Structure of the Centrosome

Functions of the Centrosome

The Centrosome in Development

CYTOSKELETON AND MOTORS: COMPLEX CYTOSKELETAL STRUCTURES | Cilia and Flagella

Structure of Cilia and Flagella

Signaling Pathways Coordinated by Cilia

Diseases Caused by Defects in Cilia

CYTOSKELETON AND MOTORS: COMPLEX CYTOSKELETAL STRUCTURES | Skeletal Muscle

Sarcomeres Are the Basic Unit of Contraction

Sarcomere Contraction Is Driven by Sliding of Myosin and Actin Filaments

Calcium Release from the SR Activates Contraction

Muscle Disorders Associated with Skeletal Muscle

CYTOSKELETON AND MOTORS: COMPLEX CYTOSKELETAL STRUCTURES | Filopodia and Lamellipodia

General Principles of Actin Polymerization-Driven Protrusion

CYTOSKELETON AND MOTORS: COMPLEX CYTOSKELETAL STRUCTURES | The Extracellular Matrix

Heparan Sulfate Proteoglycans

Other ECM Proteins Associated with Basement Membranes

FACIT Collagens and SLRPs

CYTOSKELETON AND MOTORS: COMPLEX CYTOSKELETAL STRUCTURES | Cell–Cell Adhesion and the Cytoskeleton

Cell–Cell Adhesion and the Actin Cytoskeleton

Cell–Cell Adhesion and the Intermediate Filament Cytoskeleton

Cell–Cell Adhesion and MTs

CYTOSKELETON AND MOTORS: COMPLEX CYTOSKELETAL STRUCTURES | Cell Adhesion to the Extracellular Matrix

The Extracellular Matrix (ECM)

Diversity of ECM Adhesions

Geometric and Mechanical Sensory (Mechanosensing) Functions of ECM Adhesions

The Cross-Talk between the Cell and the ECM

CYTOSKELETON AND MOTORS: COMPLEX CYTOSKELETAL STRUCTURES | Cell Migration

Alone or in the Company of Others: Modes of Eukaryotic Cell Migration

Building a Migrating Cell

Migration in Development and Homeostasis

Harnessing Cell Migration in Therapy

CYTOSKELETON AND MOTORS: COMPLEX CYTOSKELETAL STRUCTURES | Rho GTPases

Regulation of the GTP-Binding/GTP-Hydrolytic Cycles of Rho GTPases

Rho GTPases and Their Roles in Regulating the Actin Cytoskeleton

Other Targets and Multiple Roles in Biology

Rho GTPases in Oncogenic Transformation

Rho GTPases in Mammalian Tumors

Rho GTPases and Cancer Cell Metabolism

Rho GTPases and Cancer Cell Microvesicles

CYTOSKELETON AND MOTORS: COMPLEX CYTOSKELETAL STRUCTURES | Cell Polarity

Basic Principles of Cell Polarity and Common Mechanisms of Control

Apical–Basal Polarity of Epithelial Cells

Relationship between Cell Polarity and Spindle Orientation Control

Loss of Cell Polarity and Disease

INTRACELLULAR INFECTIOLOGY: CELL PROCESSES | Phagocytosis

Signaling to Actin Polymerization

Other Receptors and Signaling Pathways to Actin Polymerization

Membrane Remodeling and Focal Exocytosis

Linking Actin the Polymerization/Depolymerization Cycle with Vesicular Trafficking

Maturation of Phagosomes into Phagolysosomes

INTRACELLULAR INFECTIOLOGY: CELL PROCESSES | Macropinocytosis

Functions of Macropinocytosis

Solute Flow During Pinocytosis

Mechanisms of Macropinosome Formation

The Organization of Cytoplasm for Macropinosome Formation

INTRACELLULAR INFECTIOLOGY: CELL PROCESSES | Microbicidal Mechanisms

Phagocytes and Phagocytosis

Cell Death Mechanisms and Host Defense

Pathogen Subversion of Host Defense

INTRACELLULAR INFECTIOLOGY: CELL PROCESSES | Bacterial Subversion of Phagocytic Killing

Interference of Uptake by Bacterial Pathogens

The Replication Vacuole 1: Manipulation of the Endocytic Pathway to Support Bacterial Replication

The Replication Vacuole 2: Manipulation of the Secretory Pathway to Support Bacterial Replication

The Replication Vacuole 3: Multi-Organelle Interactions

Breaking Free to Avoid Host Cell Killing

Bypass and Exploitation of Host Autophagic Clearing of Microorganisms

Bacterial Embrace of Autophagy

INTRACELLULAR INFECTIOLOGY: CELL PROCESSES | Cellular Invasion by Bacterial Pathogens

Intracellular Lifestyle and Manipulation of Host Intracellular Trafficking

Cellular Responses to Bacterial Invasion

INTRACELLULAR INFECTIOLOGY: INFECTIOUS AGENTS | Bacterial Protein Toxins as Tools in Cell Biology and Physiology

INTRACELLULAR INFECTIOLOGY: INFECTIOUS AGENTS | The Gut Microbiome

Microbiome Research Methodology (Approaches and Tools)

Constituents of the Microbiome

The Roles of the Microbiome

Changes in the Gut Microbiome Throughout Life

Factors Influencing the Microbiome

The Microbiome and Disease

Future Microbiome Research

INTRACELLULAR INFECTIOLOGY: INFECTIOUS AGENTS | Cell Biology of Virus Infection

Introduction to the Replication Cycle

Replication and Synthesis of Viral mRNAs

Virus Assembly and Release

INTRACELLULAR INFECTIOLOGY: INFECTIOUS AGENTS | Virus Factories and Mini-Organelles Generated for Virus Replication

INTRACELLULAR INFECTIOLOGY: INFECTIOUS AGENTS | HIV – The Cell Biology of Virus Infection and Replication

The HIV Replication Cycle

Host Defences against HIV

Drugs Interfering with HIV Replication

INTRACELLULAR INFECTIOLOGY: INFECTIOUS AGENTS | Prions

History of the Prion Discovery

Conversion and Replication

INTRACELLULAR INFECTIOLOGY: CELL PROCESSES | Cellular Responses to Infections in Caenorhabditis elegans

Caenorhabditis elegans as a Model System to Study Responses to Pathogens

Overview of C. elegans Pathogens

Pathogen Recognition by C. elegans

Immune Signaling Pathways

Conclusions and Perspectives

Functional Cell Biology: An Overview

Cell Signaling and Intercellular Communication

Functional Cell Biology of Immunity

Growth Factor Mediated Cell Signaling

CELL COMMUNICATION: GROWTH FACTOR MEDIATED CELL SIGNALING | Receptor Tyrosine Kinases and Their Ligands

Families of RTKs and Their Ligands

RTKs Undergo Ligand-Induced Dimerization

Dimerization Activates the Kinase Activity of RTKs

Signaling Downstream of RTKs

Feedback and Amplification of RTK Signaling

Structural and Functional Properties of RTK Families

CELL COMMUNICATION: GROWTH FACTOR MEDIATED CELL SIGNALING | Cytokine Receptors and Their Ligands

hGHR and Related Receptors

Shared Glycoprotein 130 Receptors

Intracellular Signaling Complexes

CELL COMMUNICATION: GROWTH FACTOR MEDIATED CELL SIGNALING | TGF- β Superfamily Signaling

Function of TGF- β Superfamily Signaling

TGF- β Superfamily Ligands

TGF- β Superfamily Signaling and Disease

CELL COMMUNICATION: GROWTH FACTOR-MEDIATED CELL SIGNALING | G Protein-Coupled Receptors

G Protein-Coupled Receptors

Growth Factor Receptors and GPCRs

NGF Induces Neurite Outgrowth through G Protein

CELL COMMUNICATION: GROWTH FACTOR MEDIATED CELL SIGNALING | Guanylyl Cyclase Receptors

CELL COMMUNICATION: GROWTH FACTOR MEDIATED CELL SIGNALING | Tumor Necrosis Factor Receptors: A Brief Digestion

Structural Basis of Ligand–Receptor Interaction

Signal Transduction through TNFR Activation

The Double-Edged Sword in Cancer: Signaling through TNFR1/2 as an Example

Clinical Targeting of TNFSF and TNFRSF Members: Focusing on Cancer Immunotherapy

CELL COMMUNICATION: GROWTH FACTOR MEDIATED CELL SIGNALING | Signaling and Function of Death Receptors of the Tumor Necrosis Factor Receptor Superfamily

Introduction to Cell Death

DR Signaling Activates Multiple Signal Pathways

Function and Signaling Pathway of Each DR

CELL COMMUNICATION: GROWTH FACTOR MEDIATED CELL SIGNALING | Hedgehog Signaling in Development and Disease

The Basic Mechanisms of HH Signaling

Newer Aspects of HH Signal Transduction

HH Signaling in Human Disease

CELL COMMUNICATION: GROWTH FACTOR MEDIATED CELL SIGNALING | The Wnt/ β -Catenin Pathway

Wnt Receptors: Frizzled and LRP5/6

The ‘Wnt-Off’ State: Keeping β-Catenin Levels Low

The ‘Wnt-On’ State: Raising β -Catenin Levels High

Wnt Signaling in the Nucleus

CELL COMMUNICATION: GROWTH FACTOR MEDIATED CELL SIGNALING | The Hippo Pathway

The Hippo Pathway in D. melanogaster

Upstream Regulators of Hippo Signaling in D. melanogaster

The Hippo Pathway in Mammals

Upstream Regulators of Hippo Signaling in Mammals

Regulation of Organ Size, Stem Cell Self-Renewal, and Tissue Regeneration

Hippo Pathway Deregulation in Cancer

CELL COMMUNICATION: GROWTH FACTOR MEDIATED CELL SIGNALING | The Notch Pathway

The Notch Signaling Pathway

CELL COMMUNICATION: INTRACELLULAR PATHWAYS | SH3 and SH2: Prototypic Domains to Mediate Regulatory Mechanisms in the Cell

The Domain Perspective of Protein Architecture and Function

A Brief History of the Discovery of SH Domains

Specificity and Promiscuity

CELL COMMUNICATION: INTRACELLULAR PATHWAYS | The MAPK Signaling Cascades

Components of MAPK Cascades

Regulation of the MAPK Cascades

MAPK Signaling in Diseases

CELL COMMUNICATION: INTRACELLULAR PATHWAYS | The PI3K/Akt/mTOR Pathway

Regulation of the PI3K/Akt/mTOR Pathway

PI3K/Akt/mTOR Signaling in Human Disorders

CELL COMMUNICATION: INTRACELLULAR PATHWAYS | The JAK–STAT–SOCS Signaling Cascade

JAK–STAT–SOCS and Human Disease

CELL COMMUNICATION: INTRACELLULAR PATHWAYS | The PLC Pathway

Families of Phosphoinoside-Specific Phospholipase C Enzymes

CELL COMMUNICATION: INTRACELLULAR PATHWAYS | Calcium and Calmodulin Signaling

The EF-Hand Calcium-Binding Principle

Regulation of Ca2+ by Proteins that Mediate Its Membrane Transport

The Dark Side of Ca2+ Signaling: Ca2+-Related Pathologies

CELL COMMUNICATION: CELLULAR MACHINERIES | Macromolecular Communication between Nucleus and Cytoplasm

Transport Signals and the Importin β Superfamily: A Code

Directionality of Translocation by Importin β Superfamily Members

Related Issues/Unanticipated Roles of the Nucleus

CELL COMMUNICATION: CELLULAR MACHINERIES | The Molecular Architecture of Cell–Cell Adhesions

Cell–Cell Adhesion: The Essence of Multicellularity

Structural and Functional Diversity of Cell–Cell Junctions

The Cadherin Family and Diversity of AJs

The Molecular Basis for Cadherin–Cadherin Binding

Dynamic Connections between Cadherin and the Actin Cytoskeleton

Regulatory Elements of the Cadherin Adhesome

Cadherin and Embryonic Development

CELL COMMUNICATION: CELLULAR MACHINERIES | Extracellular Regulation of Cell-to-Matrix Adhesion

Early Studies of Cell Adhesion

Specific versus Generic Attractive and Repulsive Interactions

Stiffness, Spacing, and Curvature

How Extracellular Signals Alter Adhesion to Matrix

Cell Adhesions and Matrix Molecules in Connective Tissue Function

Role of Cell–Matrix Adhesions in Pathological Processes: Fibrosis

Role of Cell–Matrix Adhesions in Pathological Processes: Platelets and Thrombosis

CELL COMMUNICATION: CELLULAR OUTCOMES | Regulation of Cell Polarity

A Modular Signaling System

Principles of Collective Polarization

Feedback Control of Core Amplification

CELL COMMUNICATION: CELLULAR OUTCOMES | Regulation of Cell Migration

Cytoskeletal Changes Underlying Migration

Cell Migration Is Regulated Through Interactions with the Environment

Prototypic Integrative Processes

CELL COMMUNICATION: PROTOTYPIC INTEGRATIVE PROCESSES | Wound Healing: An Orchestrated Process of Cell Cycle, Adhesion, and Signaling

Molecular and Cellular Biology of Normal Wound Healing and Scar Formation

Wound Healing versus Regeneration

Impaired Wound Healing and Clinical Problems

Parallels between Wound Healing and Cancer

CELL COMMUNICATION: PROTOTYPIC INTEGRATIVE PROCESSES | Cancer Cell Invasion through Tissue Barriers

CELL COMMUNICATION: PROTOTYPIC INTEGRATIVE PROCESSES | Neuronal Transport and Spatial Signaling Mechanisms in Neural Repair

Constituents for Intracellular Communication and Trafficking in Neurons

Regulation of Cell Growth

CELL DIVISION/DEATH: REGULATION OF CELL GROWTH | mTORC1: Upstream and Downstream

CELL DIVISION/DEATH: REGULATION OF CELL GROWTH | The Nucleolus

Nucleoli and Ribosome Subunit Biogenesis

Regulation of rDNA Expression

Interchange of Nucleoli with Other Nuclear Bodies

Proteomic Studies on Nucleolar Architecture, Function, and Dynamics

CELL DIVISION/DEATH: REGULATION OF CELL GROWTH | Ribosomes and Stress – Linked from Birth to Death

Ribosome Birth in the Nucleolus

The Busy Life of the Ribosome

The End of the Line – Ribosome Degradation

CELL DIVISION/DEATH: REGULATION OF CELL GROWTH | Extra-Ribosome Functions of Ribosomal Proteins

Introduction to Basic Ribosome Structure and Function

Ribosome Biogenesis Is Intrinsically Connected to Cancerous Growth

Ribosomopathies Are Associated with Increased Cancer Risk

Non-ribosomal Functions of RPs Independent of the MDM2-p53 Pathway

Ribosomal Protein-MDM2-p53 Pathway

The RP-MDM2-p53 Pathway as a Putative Target in Cancer Therapy

CELL DIVISION/DEATH: REGULATION OF CELL GROWTH | Ribosomal RNA Processing

Ribosomal RNA Processing in Yeast

rRNA Processing in Other Eukaryotes

rRNA Processing in Prokaryotes

Human Diseases Caused by rRNA Processing Defects

CELL DIVISION/DEATH: REGULATION OF CELL GROWTH | Eukaryotic Ribosome Assembly and Export

Ribosomal Pre-rRNA Processing

Trans -Acting Factors Involved in Ribosome Assembly

Nuclear Export of Pre-Ribosomal Particles

Cytoplasmic Events in Ribosome Biogenesis

CELL DIVISION/DEATH: REGULATION OF CELL GROWTH | Internal Ribosome Entry Site-Mediated Translation

Introduction: The Canonical Cap-Dependent Mechanism of Translation Initiation in Eukaryotes

Internal Ribosome Entry Site-Mediated Translation Initiation

Conclusion and Perspective

CELL DIVISION/DEATH: REGULATION OF CELL GROWTH | Targeted mRNA Degradation

mRNA Surveillance Mechanisms

Targeted mRNA Degradation in Gene Regulation

mRNA Degradation Control by Short RNAs

Targeted mRNA Degradation by RBPs

Combined Action of Short RNAs and RBPs

CELL DIVISION/DEATH: APOPTOSIS | Apoptosis

Apoptosis, Death as Part of Life

Of Life and Apoptosis: The Anti-Apoptotic versus Pro-Apoptotic Machinery

CELL DIVISION/DEATH: APOPTOSIS | Anoikis

The Challenges of Being a Tumor Cell in its Primary Microenvironment

ROS and Anoikis – A Double-edged Sword?

What Otto Warburg Said, How It Was Misinterpreted, and the Idea of Metabolic Coupling in Tumors

CELL DIVISION/DEATH: APOPTOSIS | Mitochondria in Cell Death Regulation

Mitochondrial Control of Regulated Cell Death

Mitochondrial Membrane Permeabilization

CELL DIVISION/DEATH: APOPTOSIS | Tumor Necrosis Factor Signaling Pathways

The TNF and TNFR Superfamilies

Structural Features of TNF, TNFR1, and TNFR2

TNF-Induced TNFR Signaling

TNFR-Induced NF- κ B Activation

Regulation of TNF Signaling by Ubiquitin Ligases and Deubiquitinases

TNF-Induced Activation of MAPK Pathways

Physiologic Functions of TNF and Disease Relevance

Impact of TNF Blockade in Inflammatory Diseases

CELL DIVISION/DEATH: APOPTOSIS | Caspases

Structure, Classification, and Non-Apoptotic Biological Roles

Substrate Specificity and Targets

Caspase Activation and Function in Cell Death and Inflammation

New Modes of Caspase-Regulated Cell Death

CELL DIVISION/DEATH: APOPTOSIS | Efferocytosis in the Tumor Microenvironment

A Historical Overview of Efferocytosis

Efferocytosis Is an Established Process That Is Rapidly Deployed in the Breast

Efferocytosis in the Tumor Microenvironment

Efferocytosis and Postpartum Breast Cancer

Conclusion and Future Directions

CELL DIVISION/DEATH: APOPTOSIS | The Bcl-2 Family Proteins: Insights into Their Mechanism of Action and Therapeutic Potential

Apoptosis and the Bcl-2 Family: A Historical Perspective

How Do Bcl-2 Family Proteins Regulate MOMP?

Physiology and Regulation of Bcl-2 Family Members

Bcl-2 Proteins at the Endoplasmic Reticulum

Bcl-2 Family Proteins and Cancer

CELL DIVISION/DEATH: APOPTOSIS | Inhibitor of Apoptosis Proteins, the Sentinels of Cell Death and Signaling

Structural Organization of IAPs

IAP Protein Characteristics and Function

CELL DIVISION/DEATH: APOPTOSIS | Mitotic Catastrophe

Inducing Mitotic Catastrophe

Mechanisms of Mitotic Catastrophe

CELL DIVISION/DEATH: APOPTOSIS | Autophagy

The Autophagic Cargo and Purpose of Its Degradation

Pathophysiology of Autophagy

CELL DIVISION/DEATH: CELL CYCLE | Interplay between Oncogenes and Tumor Suppressor Genes in Human Disease

Introduction: Scope and Intent of Article

Oncogenes and Tumor Suppressor Genes and Human Cancer

Interplay between Oncogenes and Tumor Suppressor Genes in Human Cancer

Role of Oncogenes and Tumor Suppressor Genes in Human Developmental Diseases

CELL DIVISION/DEATH: CELL CYCLE | Cyclins and Cyclin-Dependent Kinases

The Discovery of Regulators of the Cell Cycle

The Cyclin-Dependent Kinases

Functions of Cyclin-CDK in the Cell Cycle and Quiescence

Cyclins, CDKs, and CKIs in Cancer

Beyond the Cell Cycle: Other Functions of Cyclins and CDKs

CELL DIVISION/DEATH: CELL CYCLE | The Restriction Point

The Role of RB and p53 in Establishing the Restriction Point

CELL DIVISION/DEATH: CELL CYCLE | CDK Inhibitors in Normal and Malignant Cells

Cyclins, CDKs, and Cell Cycle Progression

Prognostic Significance of CDK Inhibitor Deregulation in Human Cancers

CDK Inhibitors as Predictors of Drug Response

CELL DIVISION/DEATH: CELL CYCLE | The INK4a/ARF Locus

Control and Significance of G1–S Phase Progression in Mammals

p16INK4a and RB1-Mediated Senescence

INK4a/ARF – a Dual Coding Locus in Mammals

INK4a/ARF – One Locus, Two Important Tumor Suppressors

ARF, a Multi-Faceted Tumor Suppressor

Regulation and Loss of INK4a/ARF in Cancer

Unique Roles of ARF in Development

CELL DIVISION/DEATH: CELL CYCLE | S Phase

CELL DIVISION/DEATH: CELL CYCLE | Traveling through Mitosis with the Chromosomal Passenger Complex

Identification of the Core CPC Members

CPC during the Approach to Mitosis

The Spindle Assembly Checkpoint

Spindle Assembly Checkpoint and Inter-Kinetochore Tension

The Two-Histone Model of CPC Localization to Centromeres

Modified View of CPC Targeting

CPC during Anaphase, Telophase, and Cytokinesis

CELL DIVISION/DEATH: CELL CYCLE | Mitosis in Animal Cells

Mitosis As an Anticancer Drug Target

CELL DIVISION/DEATH: CELL CYCLE | Regulating Cytokinesis

Positioning the Site of Cell Division

Formation of the Cleavage Furrow

Temporal Regulation of Cytokinesis

The Abscission Checkpoint Protects against the Deleterious Effects of Chromatin Bridges

Conclusions and Future Perspectives

CELL DIVISION/DEATH: CELL CYCLE | Regulation of the p53 Pathway

Control of p53 through the Ubiquitin-Proteasome Pathway

E3 Ligases in the p53 Pathway

The p53–Mdm2–HAUSP Connection

Transactivation of p53 through Posttranslational Modifications

Involvement of p53 in Metabolism

CELL DIVISION/DEATH: CELL CYCLE | Cellular Senescence

What Defines Cellular Senescence?

Molecular Signaling Pathways

Epigenetic Control of Senescence

Senescence and Tissue Repair

Senescence in Development

CELLULAR IMMUNOLOGY: OVERVIEW | Introduction to Functional Cell Biology of Immunity

Elements of Innate and Adaptive Immunity

Barriers and Tissue Cells

Phagocytes and Their Receptors

Transcriptional Basis of B and T Cell Lineages and Memory Cells

CELLULAR IMMUNOLOGY: TRANSCRIPTIONAL BASIS OF B AND T CELL LINEAGES AND MEMORY CELLS | The T-Cell Receptor Signalosome

The TCR and Its Ligands: Structural and Functional Topology

The Signaling Code Used by the TCR Signalosome to Convert Extracellular Signals into Biological Responses

Biochemical Modules and Assembly of the TCR Signalosome

CELLULAR IMMUNOLOGY: TRANSCRIPTIONAL BASIS OF B AND T CELL LINEAGES AND MEMORY CELLS | T Follicular Helper Cells

T Follicular Helper Cell Differentiation

CELLULAR IMMUNOLOGY: TRANSCRIPTIONAL BASIS OF B AND T CELL LINEAGES AND MEMORY CELLS | V(D)J Recombination: Orchestrating Diversity without Damage

Developmental and Epigenetic Regulation of V(D)J Recombination

Molecular Mechanisms of RAG-Mediated V(D)J Recombination

V(D)J Recombination and Malignancies of the Immune System

CELLULAR IMMUNOLOGY: TRANSCRIPTIONAL BASIS OF B AND T CELL LINEAGES AND MEMORY CELLS | T Cell Memory to Viral Infections

Phenotypes of Memory T Cells

Different Phenotypes Characterize Different Viral Infections

Conclusions and Future Directions

CELLULAR IMMUNOLOGY: TRANSCRIPTIONAL BASIS OF B AND T CELL LINEAGES AND MEMORY CELLS | Nuclear Factor of Activated T Cells and Tolerance

Regulation of NFAT Activation

Functions of NFAT in T cells

NFAT and T Cell Tolerance

CELLULAR IMMUNOLOGY: TRANSCRIPTIONAL BASIS OF B AND T CELL LINEAGES AND MEMORY CELLS | NF-kappaB and the Immune System

NF- κ B in Normal Immune Cell Function and Development

Role of NF- κ B in Innate Immunity

Misregulation of NF- κ B in Human Immune Diseases

Human Immune Cell Viruses Use NF- κ B for Replication and Pathogenesis

Targeting NF- κ B for Therapy in Immune Diseases

Cell–Cell Interactions and the Immune System

CELLULAR IMMUNOLOGY: CELL–CELL INTERACTIONS AND THE IMMUNE SYSTEM | Functional Specialization of Dendritic Cell Subsets

Discovery of Dendritic Cells

Antigen Processing and Presentation

DC Development and DC Characterization

Functional Specialization in Antigen Presentation of Mouse DC Subpopulations

Functional Specialization in Antigen Presentation of Human DC Subpopulations

CELLULAR IMMUNOLOGY: CELL–CELL INTERACTIONS AND THE IMMUNE SYSTEM | CD28 Costimulation and Regulatory T Cells

How Is the Self-Tolerance Established?

The Biology of the CD28/CTLA-4 Pathway

CTLA-4 – A Key Negative Regulator of T cell Activation

Manipulation of CD28/CTLA-4 Pathway: Antagonist, Agonists, and Superagonists

CELLULAR IMMUNOLOGY: CELL–CELL INTERACTIONS AND THE IMMUNE SYSTEM | Roles of Stromal Cells in the Immune System

Introduction to Stromal Cells

Stromal Cell Regulation of Lymphoid Tissue Structure and Function

Stromal Cell Regulation of Immune Responses in Peripheral Tissues

CELLULAR IMMUNOLOGY: CELL–CELL INTERACTIONS AND THE IMMUNE SYSTEM | CXCL12/SDF-1 and Hematopoiesis

Role of CXCL12 in Homing to BM

Role of CXCL12 in HSC and HPC Maintenance within BM Niches

CXCL12 in HSC and HPC Mobilization

Role of CXCL12 in Maintenance of Neutrophils in BM

Role of CXCL12 in Maintenance of the B cell Lineage in BM

The Role of CXCL12 in Balancing Granulopoiesis and Lymphopoiesis during Inflammation

CELLULAR IMMUNOLOGY: CELL–CELL INTERACTIONS AND THE IMMUNE SYSTEM | Lymphocyte–Endothelial Interactions

The Endothelium as a Barrier for the Vascular and Lymphatic Systems

Contexts for Lymphocyte–Endothelial Interactions

Mechanisms for T Lymphocyte Adhesion to and Diapedesis across Endothelia

Information Exchange at the T Lymphocyte–Endothelial Interface

CELLULAR IMMUNOLOGY: CELL–CELL INTERACTIONS AND THE IMMUNE SYSTEM | T Cell Receptor Triggering

Time of Interaction and Recruitment of Modulators

Exclusion of Negative Regulators

Changes in Conformation and Accessibility of Intracellular Domains

Quantity and Valency of Cognate pMHC Ligands

CELLULAR IMMUNOLOGY: CELL–CELL INTERACTIONS AND THE IMMUNE SYSTEM | Single Molecule Methods to Measure Receptor–Ligand Interaction in Immunological Synapses

Mechanical Assays to Measure 2D-kinetics

Imaging TCR–pMHC Interactions In Situ

Pulling Forces Enhance Discriminative Power of Peptide Recognition

CELLULAR IMMUNOLOGY: CELL–CELL INTERACTIONS AND THE IMMUNE SYSTEM | Single-Cell Interrogation of the Immune System Using Microtools

CELLULAR IMMUNOLOGY: CELL–CELL INTERACTIONS AND THE IMMUNE SYSTEM | Cellular Structures Controlling T Cell Signaling in Time and Space

Studying the Organization of T Cell Signaling

Signaling Organization and the Structures Driving It

Signaling Organization Varies with T Cell Activation Conditions

The Function of Signaling Organization

CELLULAR IMMUNOLOGY: INNATE IMMUNITY | Function of Epithelial Barriers

Structure of the Epithelial Layer

Loss of Barrier Function in Disease

CELLULAR IMMUNOLOGY: INNATE IMMUNITY | Phagocytic Synapses

Dectin-1 Activation by β-Glucans

FcγR Activation by Immunoglobulin G (IgG)

The Phagocytic Synapse Model

Regulation of the Phagocytic Synapse by CD47

CELLULAR IMMUNOLOGY: INNATE IMMUNITY | The Phagocyte NADPH Oxidase: Structure and Assembly of the Key Multicomponent Enzyme of Innate Immunity

The Phagocyte Oxidative Burst

The Phagocyte NADPH Oxidase NOX2

CELLULAR IMMUNOLOGY: INNATE IMMUNITY | Cytoplasmic Sensing in Innate Immunity

Classes, Structure, and Activation of Innate Sensors

Role of Intracellular Organelles and Spatial Relocation

Combinatorial Sensing and PRR Crosstalk

Multiscale Regulation of Cytosolic Sensing Pathways

CELLULAR IMMUNOLOGY: INNATE IMMUNITY | Scavenger Receptors

Evolutionary Origins of SRs and Functions in Host Physiology

SRs as Causes and Therapeutic Targets in Disease

CELLULAR IMMUNOLOGY: INNATE IMMUNITY | Dendritic Cells

Discovery of Dendritic Cells

DC Development and Homeostasis

Features Enable DCs as the Orchestrator of Immunity

DCs in Clinical Immunology

CELLULAR IMMUNOLOGY: INNATE IMMUNITY | Neutrophil Biology

Neutrophil Migration into Sites of Inflammation

Neutrophil Defense Mechanisms

Genetic Defects That Affect Neutrophil Numbers and/or Function

Neutrophils in Systemic Autoimmune Diseases

CELLULAR IMMUNOLOGY: INNATE IMMUNITY | Specialized Subsets of Tissue-Resident Macrophages in Secondary Lymphoid Organs

Macrophage Subsets in the Spleen

CELLULAR IMMUNOLOGY: INNATE IMMUNITY | CD4 T Cell Memory and Role of TNF Receptor Family

Members of the TNFRSF and CD4 T Cells

STEM CELL BIOLOGY: STRUCTURE AND FUNCTION | Stem Cells and Aging

Determinants of Stem Cell Aging

Aging in Adult Stem Cells

STEM CELL BIOLOGY: STRUCTURE AND FUNCTION | Epigenetic Regulation of Stem Cells

Introduction: Regulation of Gene Expression in Stem Cells

Effectors and Mechanisms of Epigenetic Regulation of Gene Expression in ESCs

Epigenetic Signatures and Control of Nuclear Architecture in ESCs

Epigenetic Control of Quiescence/Stemness and Lineage Determination in Adult

STEM CELL BIOLOGY: STRUCTURE AND FUNCTION | The Adult Stem Cell Niche: Multiple Cellular Players in Tissue Homeostasis and Regeneration

The Adult Central Nervous System Stem Cell Niche

The Heart-Evidence for a Cardiac Stem Cell Niche?

Overall Conclusions and Future Directions

STEM CELL BIOLOGY: STRUCTURE AND FUNCTION | Cancer Stem Cells

Regulation of Cancer Stemness

Markers for the Identification of Cancer Stem Cells in Major Malignancies

Clinical Significance of Cancer Stem Cells

STEM CELL BIOLOGY: STRUCTURE AND FUNCTION | Metabolic and Energetic Regulation of Stem Cells

Hypoxia-Inducible Factor 1α and Glycolysis in Stem Cells

Fatty Acid Metabolism and Mitochondrial Function

STEM CELL BIOLOGY: STRUCTURE AND FUNCTION | Pluripotent Cells: New Tools for Disease Research and Therapies

Naturally Occurring Pluripotent Cells

Engineered Pluripotent Cells

New Tools to Provide Mechanistic Insights on Determining Cell Fates and Disease States

New Tools for Cell-Based Regenerative Therapy

Clinical Trials and Contributions to Future Cell-Based Regenerative Therapy

Systems Cell Biology: An Overview

DYNAMIC INTEGRATION: DYNAMICS | Dynamics of Gradient Sensing and Chemotaxis

Strategies for Chemotaxis

Adaptation in Chemotactic Systems

Signal Amplification and Sensitivity

DYNAMIC INTEGRATION: DYNAMICS | Modeling Actin Dynamics

Conceptual Models of Mechano-Chemical Control of Cell Motility and Shape

Detailed Biochemical Modeling

DYNAMIC INTEGRATION: DYNAMICS | Metabolism

DYNAMIC INTEGRATION: DYNAMICS | Dynamics of Microtubule Self-Assembly

Cellular Functions of Microtubules

Microtubule Self-Assembly Dynamics

Theoretical Framework for Microtubule Self-Assembly

Microtubule-Targeting Agents Attenuate Microtubule Dynamics

DYNAMIC INTEGRATION: DYNAMICS | Dynamics of Protein Kinase Cascades

Signal Amplification and Decision Making

Cellular Decisions Encoded in the Dynamics of Signaling

Robustness of Signaling Pathways

DYNAMIC INTEGRATION: DYNAMICS | Cdc42 and the Mechanisms of Yeast Cell Polarization – A Paradigm for Mesoscale Systems Biology

Cue-Dependent Cell Polarization

Inhibitory Interactions and Reinforcements in Polarity Regulation

DYNAMIC INTEGRATION: DYNAMICS | Theory of Cargo and Membrane Trafficking

Theory of the Endosomal Network

Regulation of the Microscopic Processes

Relation to Kinetics of Total Cargo Pool

Implications for Cargo Sorting

DYNAMIC INTEGRATION: DYNAMICS | Transcription Factor Networks

Global Properties of GRNs

VERTICAL INTEGRATION: MODELING | Vertical Integration

The Multiple Time and Spatial Scales Associated with Cellular Biology

Approaches for Linking Scales in Multiscale Models: ‘Top-Down’, ‘Bottom-Up,’ and ‘Middle-Out’

Mathematical and Computational Representations of the Components of a Multiscale Model

Assembling Multiscale Modeling

Software for Multiscale Modeling

Applications of Multiscale Modeling and Two Case Studies

Challenges Associated with Multiscale Modeling

VERTICAL INTEGRATION: MODELING | Computational Approaches for Multiscale Modeling

VERTICAL INTEGRATION: MODELING | Cardiac Modeling

State-of-the-Art in Cardiac Cell Modeling

Human Models of Cardiac Cell Electrophysiology

Modeling Variability in Cardiac Cell Electrophysiology

Whole Organ Cardiac Modeling

VERTICAL INTEGRATION: APPLICATIONS | Mathematical Approaches to Studying Inflammation

A Simple Mathematical Model Capturing the Resolution of Inflammation

Current Mathematical and Computational Models of Inflammation

Early Events, Leukocyte Responses to Bacteria

Inflammatory Cytokines, TNF-Therapy

Tissue Damage and Wound Healing

Inflammation and Progression to the Immune Response

Conclusions and Future Challenges

VERTICAL INTEGRATION: APPLICATIONS | Angiogenesis

Primary Factors Controlling Angiogenesis

Hypoxic Induction of Angiogenesis

Arterial and Venous Vessels

VERTICAL INTEGRATION: APPLICATIONS | A Review on Various Mathematical Modeling Approaches for Wound Healing

Wound Healing and the Need for Modeling

Evaluation of Several Mathematical Approaches

VERTICAL INTEGRATION: APPLICATIONS | Multiscale Analysis of Morphogenesis

Mathematical Models for Studying Collective Cell Behavior

Examples of Vertical Integration Studies

VERTICAL INTEGRATION: APPLICATIONS | Neurogenesis in the Adult Brain

Cell Proliferation in the SVZ

Neuronal Migration in the RMS

Neuronal Differentiation in the Olfactory Bulb

Potential Functions of Adult Neurogenesis

HORIZONTAL INTEGRATION: NETWORKS | Understanding of ‘Networks’ In Vitro and/or In Vivo

HORIZONTAL INTEGRATION: OMICS | Connecting Evolutionary Genomics to Cell Biology

Genomics for Old and New Questions

Case Studies: New Genes for Old and New Functions

HORIZONTAL INTEGRATION: OMICS | Transcriptomics

Evolution of High-Throughput Transcriptomic Technologies

Exploring the Interactive Transcriptome

New Technologies for mRNA Transcriptomics

Integrating Transcriptomics with Other Omics

HORIZONTAL INTEGRATION: OMICS | The Advent of Mass Spectrometry-Based Proteomics in Systems Biology Research

Systems Biology and Proteomics

Liquid Chromatography-Coupled Tandem Mass Spectrometry

Systems Biology Application for High-Throughput Proteomics

HORIZONTAL INTEGRATION: OMICS | Phosphoproteomics: Approaches, Developments, and Challenges

Introduction to Posttranslational Modifications

Large-Scale Phosphoproteomics Strategies

PTM Cross Talk and PTM Coding

Challenges in Phosphoproteomics

HORIZONTAL INTEGRATION: OMICS | Interactomes – Scaffolds of Cellular Systems

Methods to Map Interactomes

Applications of Interactome Maps

HORIZONTAL INTEGRATION: OMICS | Metabolomics in Cell Biology

Conducting a Successful Metabolomics Study

HORIZONTAL INTEGRATION: ANALYSES AND TOOLS | Network Modeling of Heterogeneous Datasets

HORIZONTAL INTEGRATION: ANALYSES AND TOOLS | Stochastic Analysis of Nongenetic Cell-to-Cell Heterogeneity

Variability in Gene Expression

Modeling and Analysis of Stochastic Data

Connecting Heterogeneity at Multiple Levels

HORIZONTAL INTEGRATION: ANALYSES AND TOOLS | Systematic Methods to Interrogate Genetic Perturbations and Map Phosphorylation-Dependent Signaling

HORIZONTAL INTEGRATION: ANALYSES AND TOOLS | High-Content Screening in Cell Biology

High-Content or Low-Content?

HORIZONTAL INTEGRATION: ANALYSES AND TOOLS | Integrative Systems Biology

HORIZONTAL INTEGRATION: DISEASE | Computational and Systems Cancer Biology

Integrative and Systems Biology Methodologies

Assembly and Analysis of Cancer Regulatory Models

Interactome Reverse Engineering

Interrogating Pathways and Networks

Recent Trends and Future Perspective

HORIZONTAL INTEGRATION: DISEASE | Drug Targeting

Drug Targeting – An Introduction

From Molecules to Systems

New Methods for Drug Targeting


Introduction to bioinformatics

Bioinformatics is an interdisciplinary field mainly involving molecular biology and genetics, computer science, mathematics, and statistics. Data intensive, large-scale biological problems are addressed from a computational point of view. The most common problems are modeling biological processes at the molecular level and making inferences from collected data. A bioinformatics solution usually involves the following steps: Collect statistics from biological data. Build a computational model. Solve a computational modeling problem. Test and evaluate a computational algorithm. This chapter gives a brief introduction to bioinformatics by first providing an introduction to biological terminology and then discussing some classical bioinformatics problems organized by the types of data sources. Sequence analysis is the analysis of DNA and protein sequences for clues regarding function and includes subproblems such as identification of homologs, multiple sequence alignment, searching sequence patterns, and evolutionary analyses. Protein structures are three-dimensional data and the associated problems are structure prediction (secondary and tertiary), analysis of protein structures for clues regarding function, and structural alignment. Gene expression data is usually represented as matrices and analysis of microarray data mostly involves statistics analysis, classification, and clustering approaches. Biological networks such as gene regulatory networks, metabolic pathways, and protein-protein interaction networks are usually modeled as graphs and graph theoretic approaches are used to solve associated problems such as construction and analysis of large-scale networks.


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