Why do we need autophagy? A cartoon depiction

In my role as an instructor I am constantly looking for ways to more effectively convey information to my audience, which is typically the students in my class. However, the same concerns apply to most of the people who attend a seminar. The approach you take to making the material easier to understand is likely to be influenced by the course you teach. That is, the same instructor may use different examples when teaching an upper division vs. a lower division course. I teach introductory biology, and my students may have little familiarity with cell biology, let alone autophagy. Accordingly, I have tried to consider how to illustrate the importance of autophagy in a way that can be comprehended by people who may not even be familiar with the term.     

Quantitation of NAD+: Why do we need to measure it?

Background

Nicotinamide adenine dinucleotide (NAD⁺) is an essential pyridine nucleotide that is currently investigated as an important target to extend lifespan and health span. Age-related NAD+ depletion due to the accumulation of oxidative stress is associated with reduced energy production, impaired DNA repair and genomic instability.

Why and how do we model circadian rhythms?

In our attempts to understand the circadian system, we unavoidably rely on abstractions. Instead of describing the behavior of the circadian system in all its complexity, we try to derive basic features from which we form a global concept on how the system works. Such a basic concept is a model of reality. The author discusses why it is advantageous or even necessary to transform conceptual models into mathematical formulations. As examples to demonstrate those advantages, the author reviews 4 types of mathematical models: negative feedback models thought to operate within pacemaker cells, models on coupling between pacemaker cells to generate pacemaker output, oscillator models describing the behavior of the composite circadian pacemaker, and models describing how the circadian pacemaker influences behavior.     

Examining the developing bone: What do we measure and how do we do it?

The clinical tools available to evaluate bone development in children are often ambiguous, and difficult to interpret. Unfortunately bone densitometry methods (i.e., dual energy X-ray absorptiometry, DXA) which have a relatively straightforward application in adult osteoporosis, are far more difficult to evaluate in the growing skeleton. Even with adequate "adjustment" for bone size or maturity, bone "density" (areal or volumetric) alone often gives an inaccurate assessment of bone strength--especially in children. Ideally, we would like to measure both material and geometric properties of bone to accurately estimate "strength". Mechanically meaningful measures of bone geometry (bone cross-sectional area, cortical thickness) and estimates of bending strength (section modulus, or SSI) are available with non-invasive techniques such as (p)QCT and some DXA software. With new technology it might be possible to also measure bone material properties, which will be especially important in some pediatric disorders. In children, we also need to know something about the loads imposed on a child's bone and consider not only absolute bone strength, but also the strength of bone relative to the physiologic loads. Interpreting bone strength in light of the loads imposed (particularly muscle force) is critical for an accurate diagnosis of the developing bone.     

Mechanosensitive channels: what can they do and how do they do it?

While mechanobiological processes employ diverse mechanisms, at their heart are force-induced perturbations in the structure and dynamics of molecules capable of triggering subsequent events. Among the best characterized force-sensing systems are bacterial mechanosensitive channels. These channels reflect an intimate coupling of protein conformation with the mechanics of the surrounding membrane; the membrane serves as an adaptable sensor that responds to an input of applied force and converts it into an output signal, interpreted for the cell by mechanosensitive channels. The cell can exploit this information in a number of ways: ensuring cellular viability in the presence of osmotic stress and perhaps also serving as a signal transducer for membrane tension or other functions. This review focuses on the bacterial mechanosensitive channels of large (MscL) and small (MscS) conductance and their eukaryotic homologs, with an emphasis on the outstanding issues surrounding the function and mechanism of this fascinating class of molecules.     

Why do we need drugs to treat the patient with obesity?

Objective:

Obesity is a public health problem, which increases the risk of chronic diseases and mortality. Weight loss can reduce mortality and improve most of the detrimental health consequences of obesity.

Design and Methods:

This paper was developed from two presentations to the US Food and Drug Administration (FDA), which has responsibility for reviewing and approving drugs to treat obesity.

Results:

A weight loss of 5% or more is sufficient to significantly reduce health risks in individuals with impaired glucose tolerance, hypertension, or nonalcoholic fatty liver disease. Slightly more weight loss (16% on average, achieved by surgery) reduces mortality. The goal of medicating for obesity is to help more patients achieve more weight loss. A barrier to drug approval has been the concern that weight loss medications might be used by individuals with little or no health risks, thus mandating a low side effect profile for approval of any drug. This limits the options for patients who have obesity‐related health problems that could improve with weight loss. Recently the FDA signaled interest in identifying health benefits in higher risk patients that might justify medications with higher risk; however, the potential impact on a large segment of the population has led the FDA to consider requiring a cardiovascular outcome trial for all obesity medications, either prior to or after approval.

Conclusion:

This review argues that drugs are needed for obesity because they enhance behaviorally induced weight loss and that new medications for obesity are needed in the approval process.     

What is antibiotic resistance and how can we measure it?

Antibiotic resistance is being found with increasing frequency in both pathogenic and commensal bacteria of humans and animals. Quantifying resistance within and between bacterial and host populations presents scientists with complex challenges in terms of laboratory methodologies and sampling design. Here, we discuss, from an epidemiological perspective, how antibiotic resistance can be defined and measured and the limitations of current approaches.     

How many high production chemicals are rodent carcinogens? Why should we care? What do we need to do about it?

High production volume (HPV) chemicals are produced in or imported to the US in amounts greater than 1 million pounds per chemical per year. The EPA has identified thousands of HPVs. Due to their abundance, such chemicals bring a substantial risk for human exposure, and as a result some level of adverse consequences to health are to be expected. In order to examine the potential for cancer risk associated with HPVs, this paper examines HPVs that have been tested in the National Toxicology Program's rodent cancer bioassay. The chemicals tested in the bioassay represent a small sample of the universe of environmental chemicals to which people are exposed. Unexpectedly, 60% of the 128 HPVs evaluated in the bioassay proved to be rodent carcinogens. This value compares to a predicted prevalence of only 16.5% carcinogens in a previous study. The previous study concluded that HPVs were less likely to be toxic by a variety of other test criteria as well. However, the approach involved identifying putative carcinogens using quantitative chemical structure-activity relationships (QSAR) in contrast to the direct tabulation of bioassay test results performed here. Detailed examination of bioassay results reveals that test outcomes depend heavily on route of administration as well as on dose level, sex, strain, and species used. Since most of these factors have little or no apparent relationship to chemical structure, results of this study suggest that QSAR, as well as virtually all other alternative methods, may not generally provide accurate predictions of carcinogenic potential. As we wait for efficient and effective methods for predicting carcinogens to be developed, people continue to be exposed to environmental carcinogens. Progress on regulating environmental carcinogens as well as on developing more effective test methods has been minimal since "war on cancer" began approximately 30 years ago. The present study questions whether the current strategy for dealing with environmental carcinogens will ever be successful. Close examination of rodent cancer test results seems to suggest that almost all chemicals may have carcinogenic potential in some genotypes under some exposure circumstances. If this hypothesis is correct, it would explain the general lack of progress in developing methods to differentiate carcinogens from noncarcinogens. A completely new strategy for dealing with cancer caused by exposures to environmental chemicals seems to be needed.     

The molecular biology of recombination in Mycobacteria: what do we know and how can we use it?

Recombination is a ubiquitous genetic process which results in the exchange of DNA between two substrates. Homologous recombination occurs between DNA species with identical sequence whereas illegitimate recombination can occur between DNA with very little or no homology. Site-specific recombination is often used by temperate phages to stably integrate into bacterial chromosomes. Characterisation of the mechanisms of recombination in mycobacteria has mainly focussed on RecA-dependent homologous recombination and phage-directed site-specific recombination. In contrast the high frequency of illegitimate recombination in slow-growing mycobacteria has not been explained. The role of DNA repair in dormancy and infection have not yet been fully established, but early work suggests that RecA-mediated pathways are not required for virulence. All three recombination mechanisms have been utilised in developing genetic techniques for the analysis of the biology and pathogenesis of mycobacteria. A recently developed method for studying essential genes will generate further insights into the biology of these important organisms.     

When does selective hunting select,how can we tell,and what should we do about it?

Potential evolutionary consequences of selective hunting of mammals are controversial because of limited evidence and important socio‐economic impacts. Several ecological and management variables facilitate evolutionary responses to selection for horn, tusk or antler size, including strong selective hunting pressure; harvest of males with large horns, tusks or antlers before they can breed; unavailable or ineffective sources of unselected immigrants; and age‐dependent relationships between horn, tusk or antler size and male mating success. Plastic responses of male horns, tusks and antlers to environment are probably more common than evolutionary changes. Evidence for evolutionary effects of selective hunting is strong for large mammals where biological characteristics and hunting regulations combine to favour them.     

What to do, or how to do it?

In this issue of Neuron, Ajemian et al. present a computational model of the activity of neurons in primary motor cortex (M1) during isometric movements in different postures. By modeling the output of M1 neurons in terms of their influence on muscles, they find each M1 neuron maps its output into a particular pattern of muscle actions.     

From co-expression to co-regulation: how many microarray experiments do we need?

Background  

Cluster analysis is often used to infer regulatory modules or biological function by associating unknown genes with other genes that have similar expression patterns and known regulatory elements or functions. However, clustering results may not have any biological relevance.     

Fish cognition: what can we learn, and what do they need to learn?

Fish provide a wonderful opportunity to explore processes that shape and select cognitive ability. In this presentation, I will illustrate three aspects of work that my colleagues and I have used to investigate fish learning and memory over the last decade. First, I will discuss how comparing different populations sampled from contrasting habitats allows differences in cognitive ability to be related to the evolutionary ecology of the fish. I will use examples that have investigated how differences in learning ability between populations of the same species can arise. Here, the examples will be taken from the ubiquitous three‐spined stickleback, and a Panamanian poecilid, Brachyraphis .
The second approach has used fish cognition as a tool to quantify behaviour to enable assessment of different aspects of fish welfare. For example, the recent work investigating pain perception in trout required the use of a learning task to quantify how fish behaviour was modified after noxious stimulation. Ways in which these, and similar, processes can be used in future studies of fish welfare will be discussed.
The final part of the presentation will consider recent work that addresses the problems of releasing hatchery‐reared fish for restocking purposes. Although a common practice, most of the hatchery‐reared fish die shortly after they are released. Much of the observed mortality apparently stems from the fishes' inexperience with a variable environment. Experiments with juvenile cod and brown trout suggest that both age, and the early rearing environment, have profound effects on fish learning and behaviour. I will discuss how simple modifications to current rearing practices may have large beneficial effects on the post‐release survival of hatchery‐reared fish.     

Adaptive developmental plasticity: what is it,how can we recognize it and when can it evolve?

Developmental plasticity describes situations where a specific input during an individual''s development produces a lasting alteration in phenotype. Some instances of developmental plasticity may be adaptive, meaning that the tendency to produce the phenotype conditional on having experienced the developmental input has been under positive selection. We discuss the necessary assumptions and predictions of hypotheses concerning adaptive developmental plasticity (ADP) and develop guidelines for how to test empirically whether a particular example is adaptive. Central to our analysis is the distinction between two kinds of ADP: informational, where the developmental input provides information about the future environment, and somatic state-based, where the developmental input enduringly alters some aspect of the individual''s somatic state. Both types are likely to exist in nature, but evolve under different conditions. In all cases of ADP, the expected fitness of individuals who experience the input and develop the phenotype should be higher than that of those who experience the input and do not develop the phenotype, while the expected fitness of those who do not experience the input and do not develop the phenotype should be higher than those who do not experience the input and do develop the phenotype. We describe ancillary predictions that are specific to just one of the two types of ADP and thus distinguish between them.