Race, ethnicity, and health: can genetics explain disparities?

Over the past decade, numerous studies have documented profound racial and ethnic disparities in disease in the United States. This essay examines how popular and scientific concepts of race and ethnicity converge with dominant understandings of genetics to inform the design and interpretation of research, public health policy, and medical practice. Although there is some acknowledgment in the biomedical community that racial and ethnic categories are social and not genetic, ideas about race and ethnicity that circulate in biomedicine are contradictory. Thus, in practice genetic explanations for observed differences are common both in the scientific literature and in popular media accounts of biomedical research. Such explanations naturalize racial and ethnic difference and create a conceptual barrier to developing a research program that explores the complex ways in which social inequality and experiences of racial discrimination interact with human biology to influence patterns of disease. Importantly, genetically based ideas lead to disease prevention policies that are bound to be ineffective.     

Sex and death: what is the connection?

A cost of reproduction, where lifespan and fecundity are negatively correlated, is of widespread occurrence. Mutations in insulin/IGF signaling (IIS) pathways and dietary restriction (DR) can extend lifespan in model organisms but do not always reduce fecundity, suggesting that the link between lifespan and fecundity is not inevitable. Understanding the molecular basis of the cost of reproduction will be informed by elucidation of the mechanisms by which DR and IIS affect these two traits.     

Autophagy and apoptosis: what is the connection?

The therapeutic potential of autophagy for the treatment cancer and other diseases is beset by paradoxes stemming from the complexity of the interactions between the apoptotic and autophagic machinery. The simplest question of how autophagy acts as both a protector and executioner of cell death remains the subject of substantial controversy. Elucidating the molecular interactions between the processes will help us understand how autophagy can modulate cell death, whether autophagy is truly a cell death mechanism, and how these functions are regulated. We suggest that, despite many connections between autophagy and apoptosis, a strong causal relationship wherein one process controls the other, has not been demonstrated adequately. Knowing when and how to modulate autophagy therapeutically depends on understanding these connections.     

Statin therapy and stroke prevention: what was known, what is new and what is next?

PURPOSE OF REVIEW: Randomized trials have shown that statins may reduce the risk of primary stroke. There is no evidence however that statins can reduce recurrent stroke incidence. RECENT FINDINGS: In the SPARCL trial, patients with a recent stroke or transient ischemic attack randomized to atorvastatin 80 mg/day had a significant 16% relative risk reduction of stroke, and a 35% reduction in major coronary events compared with placebo. This was obtained despite 25% of the placebo arm patients receiving a commercially-available statin outside of the trial. Post-hoc analysis used blinded LDL-cholesterol measurements as a marker of adherence to lipid-lowering therapy. Compared with the group with no change or an increase in LDL-cholesterol (the group adherent to placebo or not taking a statin), the group with over 50% reduction in LDL-cholesterol had a significant 31% reduction in stroke. The next step is to define whether achieving LDL-cholesterol below 70 mg/dl is better than a standard dose of statin (LDL around 100-110 mg/dl) in the secondary prevention of stroke. SUMMARY: Statins are effective in reducing both first-ever and recurrent stroke, and this effect seems driven by the extent of LDL-cholesterol lowering.     

Vaccination against shigellosis: is it the path that is difficult or is it the difficult that is the path?

Following several decades of research, there is not yet a convincing vaccine against shigellosis. It is still difficult, in spite of the breadth of strategies (i.e. live attenuated oral, killed oral, subunit parenteral) to select an optimal option. Two approaches are clearly emerging: (i) live attenuated deletion mutants based on rational selection of genes that are key in the pathogenic process, and (ii) conjugated detoxified polysaccharide parenteral vaccines, or more recently conjugated synthetic carbohydrates. Some of these approaches have already undergone phase I and II clinical trials with promising results, but important issues have also emerged, particularly the discrepancy between colonization and immunogenic potential of live attenuated vaccine candidates depending upon the population concerned (i.e. non endemic vs. endemic areas). Efforts are needed to definitely establish the proof of concept of these approaches, and thus the need for clinical trials which should also soon explore the possibility to associate different serotypes, in response to serotype specific protection against shigellosis. More basic research is also required to improve what we can still consider as first-generation vaccines, and to explore possible new paradigms including the search for cross-protective antigens.     

If neuroimaging is the answer,what is the question?

It is unclear that we will come to a better understanding of mental processes simply by observing which neural loci are activated while subjects perform a task. Rather, I suggest here that it is better to come armed with a question that directs one to design tasks in ways that take advantage of the strengths of neuroimaging techniques (particularly positron emission tomography and functional magnetic resonance imaging). Here I develop a taxonomy of types of questions that can be easily addressed by such techniques. The first class of questions focuses on how information processing is implemented in the brain; these questions can be posed at a very coarse scale, focusing on the entire system that confers a particular ability, or at increasingly more specific scales, ultimately focusing on individual structures or processes. The second class of questions focuses on specifying when particular processes and structures are invoked; these questions focus on how one can use patterns of activation to infer that specific processes and structures were invoked, and on how processing changes in different circumstances. The use of neuroimaging to address these questions is illustrated with results from experiments on visual cognition, and caveats regarding the logic of inference in each case are noted. Finally, the necessary interplay between neuroimaging and behavioural studies is stressed.     

Coxiella burnetii: what is the reality?

After the Second World War, in Italy Q Fever or Coxiellosis has been shown a significant relevance, a recrudescence with an epidemic state for over ten years. Later, the infectious disease occurred as endemic since the 80s, the outbreaks were just isolated. Workflows analysis of some authors has demonstrated the spread out of the infection throughout Italian herds with a prevalence ranging from 1.2 per cent to 10 per cent. Our survey carried out throughout Campania area in cattle has shown a real positivity over 14 per cent performing the IFAT for the detection of IgG antibodies for Coxiella burnetii. Therefore, it has been so important to stress the influence of cattle farming management in stables as a real risk of Coxiellosis. For example, the Relative Risk (RR) has been registrated about 6.84 (2.18相似文献   

Ontogeny and the fossil record: what,if anything,is an adult dinosaur?

Identification of the ontogenetic status of an extinct organism is complex, and yet this underpins major areas of research, from taxonomy and systematics to ecology and evolution. In the case of the non-avialan dinosaurs, at least some were reproductively mature before they were skeletally mature, and a lack of consensus on how to define an ‘adult’ animal causes problems for even basic scientific investigations. Here we review the current methods available to determine the age of non-avialan dinosaurs, discuss the definitions of different ontogenetic stages, and summarize the implications of these disparate definitions for dinosaur palaeontology. Most critically, a growing body of evidence suggests that many dinosaurs that would be considered ‘adults’ in a modern-day field study are considered ‘juveniles’ or ‘subadults’ in palaeontological contexts.     

The manganese/iron-carboxylate proteins: what is what, where are they, and what can the sequences tell us?

The manganese/iron-carboxylate proteins make up a recently discovered group of proteins that contain a heterodinuclear Mn/Fe redox cofactor. The chemical potential of the heterodinuclear metal site is just starting to be characterized, but available data suggest that it may have capabilities for similarly versatile chemistry as the extensively studied diiron-carboxylate cofactor. The presently identified members of the manganese/iron-carboxylate proteins are all sequence homologues of the radical-generating R2 subunit of class I ribonucleotide reductase, canonically a diiron protein. They are also commonly misannotated as such in databases. In spite of the sequence similarity, the manganese/iron-carboxylate proteins form at least two functionally distinct groups, radical-generating ribonucleotide reductase subunits and ligand-binding Mn/Fe proteins. Here, the presently available sequences for the manganese/iron-carboxylate proteins are gathered, grouped, and analyzed. The analysis provides sequence determinants that allow group identification of new sequences on the single-protein level. Key differences between the groups are mapped on the known representative structures, providing clues to the structural prerequisites for metal specificity, cofactor formation, and difference in function. The organisms that encode manganese/iron-carboxylate proteins are briefly discussed; their environmental preference suggests that the Mn/Fe heterodinuclear cofactor is preferred by extremophiles and pathogens with a particularly high relative presence in Archaea.     

What is signal and what is noise in the brain?

The response of a cortical neuron to a stimulus can show a very large variability when repeatedly stimulated by exactly the same stimulus. This has been quantified in terms of inter-spike-interval (ISI) statistics by several researchers (e.g., [Softky, W., Koch, C., 1993. The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. J. Neurosci. 13(1), 334-350.]). The common view is that this variability reflects noisy information processing based on redundant representation in large neuron populations. This view has been challenged by the idea that the apparent noise inherent in brain activity that is not strictly related or temporally coupled to the experiment could be functionally significant. In this work we examine the ISI statistics and discuss these views in a recently published model of interacting cortical areas [Knoblauch, A., Palm, G., 2002. Scene segmentation by spike synchronization in reciprocally connected visual areas. I. Local effects of cortical feedback. Biol. Cybernet. 87(3), 151-167.]. From the results of further single neuron simulations we can isolate temporally modulated synaptic input as a main contributor for high ISI variability in our model and possibly in real neurons. In contrast to alternative mechanisms, our model suggests a function of the temporal modulations for short-term binding and segmentation of figures from background. Moreover, we show that temporally modulated inputs lead to ISI statistics which fit better to the neurophysiological data than alternative mechanisms.     

Vaults are the answer, what is the question?

Vaults are large cytoplasmic ribonucleoprotein (RNP) particles of eukaryotic cells, whose considerable abundance and striking evolutionary conservation argue for an important general cellular function. Early studies on vaults focused on the structural features and cellular distribution of the particle and will only be summarized briefly here. In this article, we discuss the molecular characterization of vault components and describe genetic studies carried out in Dictyostelium. The recent finding that the major vault protein is elevated in non-P-glycoprotein multidrug resistant cancer cells has direct implications concerning the function of the vault particle and indicates a potential role for vaults in resistance of tumour cells to anticancer drugs.     

Insect thermal tolerance: what is the role of ontogeny,ageing and senescence?

Temperature has dramatic evolutionary fitness consequences and is therefore a major factor determining the geographic distribution and abundance of ectotherms. However, the role that age might have on insect thermal tolerance is often overlooked in studies of behaviour, ecology, physiology and evolutionary biology. Here, we review the evidence for ontogenetic and ageing effects on traits of high- and low-temperature tolerance in insects and show that these effects are typically pronounced for most taxa in which data are available. We therefore argue that basal thermal tolerance and acclimation responses (i.e. phenotypic plasticity) are strongly influenced by age and/or ontogeny and may confound studies of temperature responses if unaccounted for. We outline three alternative hypotheses which can be distinguished to propose why development affects thermal tolerance in insects. At present no studies have been undertaken to directly address these options. The implications of these age-related changes in thermal biology are discussed and, most significantly, suggest that the temperature tolerance of insects should be defined within the age-demographics of a particular population or species. Although we conclude that age is a source of variation that should be carefully controlled for in thermal biology, we also suggest that it can be used as a valuable tool for testing evolutionary theories of ageing and the cellular and genetic basis of thermal tolerance.