Genetics of Obesity: What have we Learned?

Candidate gene and genome-wide association studies have led to the discovery of nine loci involved in Mendelian forms of obesity and 58 loci contributing to polygenic obesity. These loci explain a small fraction of the heritability for obesity and many genes remain to be discovered. However, efforts in obesity gene identification greatly modified our understanding of this disorder. In this review, we propose an overlook of major lessons learned from 15 years of research in the field of genetics and obesity. We comment on the existence of the genetic continuum between monogenic and polygenic forms of obesity that pinpoints the role of genes involved in the central regulation of food intake and genetic predisposition to obesity. We explain how the identification of novel obesity predisposing genes has clarified unsuspected biological pathways involved in the control of energy balance that have helped to understand past human history and to explore causality in epidemiology. We provide evidence that obesity predisposing genes interact with the environment and influence the response to treatment relevant to disease prediction.     

Six Years of Criticality Assessments: What Have We Learned So Far?

The “criticality” of the various elements used in modern technologies is a topic of increasing interest, with groups from governments, consultancies, and academic institutions developing a variety of methodologies and using them to make assessments. Other groups from similar organizations are studying the methodologies that generate these assessments. Here, we analyze the different types of studies, review issues of methodology, and comment on features of nine different studies published between 2008 and mid‐2014. From these studies, we derive lists of problematic, debatable, and desirable aspects of criticality studies. We emphasize that the criticality of an element can vary depending on the target organization and that, because criticality is a dynamic state, it must be periodically re‐evaluated. There is substantial value to be derived if a more uniform methodology could be developed. We discuss how a harmonized methodological framework might be achieved and what its benefits could be. Putting into place such a structure for collaborative and publicly available criticality determinations would be very likely to better serve the present and future needs of corporations and governments than is the case at present, where different methodologies generate different results.     

The Vaginal Microbiota: What Have We Learned after a Decade of Molecular Characterization?

We conducted a systematic review of the Medline database (U.S. National Library of Medicine, National Institutes of Health, Bethesda, MD, U.S.A) to determine if consistent molecular vaginal microbiota (VMB) composition patterns can be discerned after a decade of molecular testing, and to evaluate demographic, behavioral and clinical determinants of VMB compositions. Studies were eligible when published between 1 January 2008 and 15 November 2013, and if at least one molecular technique (sequencing, PCR, DNA fingerprinting, or DNA hybridization) was used to characterize the VMB. Sixty three eligible studies were identified. These studies have now conclusively shown that lactobacilli-dominated VMB are associated with a healthy vaginal micro-environment and that bacterial vaginosis (BV) is best described as a polybacterial dysbiosis. The extent of dysbiosis correlates well with Nugent score and vaginal pH but not with the other Amsel criteria. Lactobacillus crispatus is more beneficial than L. iners. Longitudinal studies have shown that a L. crispatus-dominated VMB is more likely to shift to a L. iners-dominated or mixed lactobacilli VMB than to full dysbiosis. Data on VMB determinants are scarce and inconsistent, but dysbiosis is consistently associated with HIV, human papillomavirus (HPV), and Trichomonas vaginalis infection. In contrast, vaginal colonization with Candida spp. is more common in women with a lactobacilli-dominated VMB than in women with dysbiosis. Cervicovaginal mucosal immune responses to molecular VMB compositions have not yet been properly characterized. Molecular techniques have now become more affordable, and we make a case for incorporating them into larger epidemiological studies to address knowledge gaps in etiology and pathogenesis of dysbiosis, associations of different dysbiotic states with clinical outcomes, and to evaluate interventions aimed at restoring and maintaining a lactobacilli-dominated VMB.     

IRIS and Fungal Infections: What Have We Learned?

Restoration of pathogen-specific immunity as a result of highly active antiretroviral therapy or reduction of immunosuppression in solid-organ transplant recipients can result in a destructive inflammatory response known as the immune reconstitution inflammatory syndrome (IRIS). Though immune reconstitution disorders can occur in the context of a number of infectious and neoplastic processes, IRIS associated with invasive mycoses, in particular cryptococcosis, is a highly prevalent and morbid entity worldwide. Recent consensus definitions and prospective analyses of cryptococcal IRIS, with particular attention to baseline clinical features, serum and cerebrospinal fluid biomarkers, and the evolution of these over time in individual patients have provided critical insights into pathogenesis. This review focuses on the current understanding of IRIS in the context of opportunistic mycoses, with particular attention to Cryptococcus infection, and discusses the basis for this understanding, including biomarkers as clues to pathogenesis and aids in diagnosis and novel approaches to prevention and management.     

Retention of Memory through Metamorphosis: Can a Moth Remember What It Learned As a Caterpillar?

Insects that undergo complete metamorphosis experience enormous changes in both morphology and lifestyle. The current study examines whether larval experience can persist through pupation into adulthood in Lepidoptera, and assesses two possible mechanisms that could underlie such behavior: exposure of emerging adults to chemicals from the larval environment, or associative learning transferred to adulthood via maintenance of intact synaptic connections. Fifth instar Manduca sexta caterpillars received an electrical shock associatively paired with a specific odor in order to create a conditioned odor aversion, and were assayed for learning in a Y choice apparatus as larvae and again as adult moths. We show that larvae learned to avoid the training odor, and that this aversion was still present in the adults. The adult aversion did not result from carryover of chemicals from the larval environment, as neither applying odorants to naïve pupae nor washing the pupae of trained caterpillars resulted in a change in behavior. In addition, we report that larvae trained at third instar still showed odor aversion after two molts, as fifth instars, but did not avoid the odor as adults, consistent with the idea that post-metamorphic recall involves regions of the brain that are not produced until later in larval development. The present study, the first to demonstrate conclusively that associative memory survives metamorphosis in Lepidoptera, provokes intriguing new questions about the organization and persistence of the central nervous system during metamorphosis. Our results have both ecological and evolutionary implications, as retention of memory through metamorphosis could influence host choice by polyphagous insects, shape habitat selection, and lead to eventual sympatric speciation.     

Instant Transformation of Learned Repulsion into Motivational “Wanting”

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Highlights? Motivation is the product of past experience and current mesocorticolimbic state ? Novel appetite state transforms a repulsive salt cue into a motivational magnet ? The cue becomes avidly “wanted,” despite knowledge that the salt always tastes disgusting ? This dynamic transformation recruits brain mesocorticolimbic circuitry     

What became of Hystrix?

Hystrix Moench was a perennial genus of the Triticeae. Its members differed from those of other genera in the tribe in lacking glumes. The type species is H. patulaMoench, a North American taxon. When it became accepted that H. patula should be included in Elymus, Hystrix could not be used as a generic name. The problem became how to treat the other species that had been included in Hystrix. Hystrix patula, like many other species of Elymus, has the StH genomic composition but H. coreana (Honda) Ohwi, H. californica (Bol.) Kuntze, H. duthiei (Stapf) Bor ssp. duthiei, and H. duthiei ssp. longearistata have the NsXm genomic composition that is associated with Leymus. Using genomic in situ hybridization analysis, we showed that H. komarovii (Roshev.) Ohwi has an NsE^e genomic composition, a combination not known from any other species. Hystrix sibirica (Trautv.) Kuntze and H. duthiei ssp. japonica are included in Leymus on morphological grounds. The status of H. kunlunensis K. S. Hao is not clear. In this paper, we summarize our results and those of others concerning what is now known and the problems that remain concerning the species that used to be included in Hystrix.     

Antibiotic Use in Animal Agriculture: What Have We Learned and Where are We Going?

Antibiotics are enormously important for the humane and efficient production of food animals. These benefits are somewhat offset by the human and animal health antibiotic resistance risks posed by their use in animals. This article provides an overview of what we have learned about antibiotic resistance as an issue in animal agriculture and where that knowledge could lead us in the future. To preserve the effectiveness of antibiotics, more action is needed to ensure their prudent use, particularly in the case of antibiotic growth promoters and antibiotics deemed critically important for human and animal health.     

The Enemy as a Patient: What can be Learned from the Emotional Experience of Physicians and Why does it Matter Ethically?

This qualitative research examines the influence of animosity on physicians during clinical encounters and its ethical implications. Semi‐structured interviews were conducted with ten Israeli‐Jewish physicians: four treated Syrians and six treated Palestinian terrorists/Hezbollah militants or Palestinian civilians. An interpretive phenomenological analysis was used to uncover main themes in these interviews. Whereas the majority of physicians stated they are obligated to treat any patient, physicians who treated Syrians exhibited stronger emotional expression and implicit empathy, while less referring to the presence of the Israeli‐Arab conflict. In contrast, physicians who treated enemy combatants or Palestinian civilians showed the exact opposite. Linking these results to the “Implicit Bias” theory, the role of empathy and the beneficence principle in medical ethics, we argue that: (a) the unconscious decreased emotional involvement among the latter group of physicians is a deficiency that needs to be recognized; and (b) this deficiency undermines the principle of beneficence, thereby possibly influencing the fulfillment of the commitment to treat patients. Acknowledging and addressing the potential emotional and ethical deficiencies entailed in encounters with the so‐called enemy‐patients are of importance to the global medical community, since such encounters are increasingly an integral part of the current political realities faced by both the developed and developing worlds.     

What is the function of centrioles?

The function of centrioles has been controversial and remains incompletely resolved. This is because centrioles, in and of themselves, do not directly perform any physiological activity. Instead, their role is only to act as a jig or breadboard onto which other functional structures can be built. Centrioles are primarily involved in forming two structures-centrosomes and cilia. Centrioles bias the position of spindle pole formation, but because spindle poles can self-organize, the function of the centriole in mitosis is not obligatory. Consequently, lack of centrioles does not generally prevent mitosis, although recent experiments suggest acentriolar spindles have reduced fidelity of chromosome segregation. In contrast, centrioles are absolutely required for the assembly of cilia, including primary cilia that act as cellular antennae. Consistent with this requirement, it is now becoming clear that many ciliary diseases, including nephronophthisis, Bardet-Biedl syndrome, Meckel Syndrome, and Oral-Facial-Digital syndrome, are caused by defects in centriole-associated proteins.     

What Is the Tree of Life?

A universal Tree of Life (TOL) has long been a goal of molecular phylogeneticists, but reticulation at the level of genes and possibly at the levels of cells and species renders any simple interpretation of such a TOL, especially as applied to prokaryotes, problematic.One of the several ways in which microbiology puts the neo-Darwinian synthesis in jeopardy is by the threatening to “uproot the Tree of Life (TOL)” [1]. Lateral gene transfer (LGT) is much more frequent than most biologists would have imagined up until about 20 years ago, so phylogenetic trees based on sequences of different prokaryotic genes are often different. How to tease out from such conflicting data something that might correspond to a single, universal Tree of Life becomes problematic. Moreover, since many important evolutionary transitions involve lineage fusions at one level or another, the aptness of a tree (a pattern of successive bifurcations) as a summary of life’s history is uncertain [2–4].