The Elusive Structure of Centro-Chromatin: Molecular Order or Dynamic Heterogenetity?

The centromere is an essential chromatin domain required for kinetochore recruitment and chromosome segregation in eukaryotes. To perform this role, centro-chromatin adopts a unique structure that provides access to kinetochore proteins and maintains stability under tension during mitosis. This is achieved by the presence of nucleosomes containing the H3 variant CENP-A, which also acts as the epigenetic mark defining the centromere. In this review, we discuss the role of CENP-A on the structure and dynamics of centromeric chromatin. We further discuss the impact of the CENP-A binding proteins CENP-C, CENP-N, and CENP-B on modulating centro-chromatin structure. Based on these findings we provide an overview of the higher order structure of the centromere.     

Global Epidemiology of Mental Disorders: What Are We Missing?

Background

Population-based studies provide the understanding of health-need required for effective public health policy and service-planning. Mental disorders are an important but, until recently, neglected agenda in global health. This paper reviews the coverage and limitations in global epidemiological data for mental disorders and suggests strategies to strengthen the data.

Methods

Systematic reviews were conducted for population-based epidemiological studies in mental disorders to inform new estimates for the global burden of disease study. Estimates of population coverage were calculated, adjusted for study parameters (age, gender and sampling frames) to quantify regional coverage.

Results

Of the 77,000 data sources identified, fewer than 1% could be used for deriving national estimates of prevalence, incidence, remission, and mortality in mental disorders. The two major limitations were (1) highly variable regional coverage, and (2) important methodological issues that prevented synthesis across studies, including the use of varying case definitions, the selection of samples not allowing generalization, lack of standardized indicators, and incomplete reporting. North America and Australasia had the most complete prevalence data for mental disorders while coverage was highly variable across Europe, Latin America, and Asia Pacific, and poor in other regions of Asia and Africa. Nationally-representative data for incidence, remission, and mortality were sparse across most of the world.

Discussion

Recent calls to action for global mental health were predicated on the high prevalence and disability of mental disorders. However, the global picture of disorders is inadequate for planning. Global data coverage is not commensurate with other important health problems, and for most of the world''s population, mental disorders are invisible and remain a low priority.     

Alzheimer’s Disease: Analyzing the Missing Heritability

Alzheimer’s disease (AD) is a complex disorder influenced by environmental and genetic factors. Recent work has identified 11 AD markers in 10 loci. We used Genome-wide Complex Trait Analysis to analyze >2 million SNPs for 10,922 individuals from the Alzheimer’s Disease Genetics Consortium to assess the phenotypic variance explained first by known late-onset AD loci, and then by all SNPs in the Alzheimer’s Disease Genetics Consortium dataset. In all, 33% of total phenotypic variance is explained by all common SNPs. APOE alone explained 6% and other known markers 2%, meaning more than 25% of phenotypic variance remains unexplained by known markers, but is tagged by common SNPs included on genotyping arrays or imputed with HapMap genotypes. Novel AD markers that explain large amounts of phenotypic variance are likely to be rare and unidentifiable using genome-wide association studies. Based on our findings and the current direction of human genetics research, we suggest specific study designs for future studies to identify the remaining heritability of Alzheimer’s disease.     

The Circadian System and Affective Disorders: Clocks or Rhythms?

There have been a number of proposals that a pathology of the circadian system involving clock functioning underlies the affective disorders. It is argued that neither current findings from research into the neurophysiological substrates of the affective disorders, recent clinical findings regarding these illnesses or their phenomenology support such a contention. This does not mean however that there is not a primary pathological disturbance of the circadian system at the heart of the affective disorders. The same neurophysiological, phenomenological and clinical evidence can be offered in favour of a disturbance of circadian rhythms in the presence of grossly normal clock functioning. The research and remedial implications of this alternative are outlined briefly.     

Evolution and University-level Anthropology Textbooks: The “Missing Link”?

Although studies analyzing the content of evolution curriculum usually focus on courses within the context of a biological sciences department or program, research must also address students and courses outside of the biological sciences. For example, using data solely from biological courses will not fully represent the scope of coverage of evolution in university education, as other fields, like anthropology, also utilize evolutionary principles. We analyzed the content of 31 university-level anthropology textbooks for the following: (1) presence of a definition of evolution in various sections of the textbooks, (2) accuracy and consistency of the definitions provided in the textbook sections, and (3) differences between textbooks for cultural and physical anthropology. Results of this study suggest that anthropology textbooks do not necessarily (1) provide a single definition of evolution or (2) provide an accurate, “baseline” definition of evolution when present. Additionally, substantive differences were observed between definitions provided in different sections within a single textbook, as well as between textbooks written for cultural anthropology and physical anthropology/archaeology courses. Given the inclusion of anthropology courses in general education curriculum at the university-level, we conclude that this situation may further exacerbate the misunderstanding of the basic tenets of evolution that university students have been repeatedly shown to demonstrate. We stress the role of the instructor in choosing textbooks that provide accurate information for students, as well as the responsibility they hold in providing a concise, accurate definition of evolution in social sciences courses.     

The Diversity of Coral Reefs: What Are We Missing?

Tropical reefs shelter one quarter to one third of all marine species but one third of the coral species that construct reefs are now at risk of extinction. Because traditional methods for assessing reef diversity are extremely time consuming, taxonomic expertise for many groups is lacking, and marine organisms are thought to be less vulnerable to extinction, most discussions of reef conservation focus on maintenance of ecosystem services rather than biodiversity loss. In this study involving the three major oceans with reef growth, we provide new biodiversity estimates based on quantitative sampling and DNA barcoding. We focus on crustaceans, which are the second most diverse group of marine metazoans. We show exceptionally high numbers of crustacean species associated with coral reefs relative to sampling effort (525 species from a combined, globally distributed sample area of 6.3 m(2)). The high prevalence of rare species (38% encountered only once), the low level of spatial overlap (81% found in only one locality) and the biogeographic patterns of diversity detected (Indo-West Pacific>Central Pacific>Caribbean) are consistent with results from traditional survey methods, making this approach a reliable and efficient method for assessing and monitoring biodiversity. The finding of such large numbers of species in a small total area suggests that coral reef diversity is seriously under-detected using traditional survey methods, and by implication, underestimated.     

The Elusive Baseline of Marine Disease: Are Diseases in Ocean Ecosystems Increasing?

Disease outbreaks alter the structure and function of marine ecosystems, directly affecting vertebrates (mammals, turtles, fish), invertebrates (corals, crustaceans, echinoderms), and plants (seagrasses). Previous studies suggest a recent increase in marine disease. However, lack of baseline data in most communities prevents a direct test of this hypothesis. We developed a proxy to evaluate a prediction of the increasing disease hypothesis: the proportion of scientific publications reporting disease increased in recent decades. This represents, to our knowledge, the first quantitative use of normalized trends in the literature to investigate an ecological hypothesis. We searched a literature database for reports of parasites and disease (hereafter “disease”) in nine marine taxonomic groups from 1970 to 2001. Reports, normalized for research effort, increased in turtles, corals, mammals, urchins, and molluscs. No significant trends were detected for seagrasses, decapods, or sharks/rays (though disease occurred in these groups). Counter to the prediction, disease reports decreased in fishes. Formulating effective resource management policy requires understanding the basis and timing of marine disease events. Why disease outbreaks increased in some groups but not in others should be a priority for future investigation. The increase in several groups lends urgency to understanding disease dynamics, particularly since few viable options currently exist to mitigate disease in the oceans.     

The Genetic Correlation between Height and IQ: Shared Genes or Assortative Mating?

Traits that are attractive to the opposite sex are often positively correlated when scaled such that scores increase with attractiveness, and this correlation typically has a genetic component. Such traits can be genetically correlated due to genes that affect both traits (“pleiotropy”) and/or because assortative mating causes statistical correlations to develop between selected alleles across the traits (“gametic phase disequilibrium”). In this study, we modeled the covariation between monozygotic and dizygotic twins, their siblings, and their parents (total N = 7,905) to elucidate the nature of the correlation between two potentially sexually selected traits in humans: height and IQ. Unlike previous designs used to investigate the nature of the height–IQ correlation, the present design accounts for the effects of assortative mating and provides much less biased estimates of additive genetic, non-additive genetic, and shared environmental influences. Both traits were highly heritable, although there was greater evidence for non-additive genetic effects in males. After accounting for assortative mating, the correlation between height and IQ was found to be almost entirely genetic in nature. Model fits indicate that both pleiotropy and assortative mating contribute significantly and about equally to this genetic correlation.     

The evolution of regeneration: adaptive or inherent?

If regeneration were adaptive, it would have arisen autonomously by natural selection from non-regenerative antecedents. Unless each episode coincidentally reinvented the same method of regeneration independently, one would expect the various lineages to differ basically from each other, which they do not. On the other hand, if regeneration were inherent to metazoan life, a derivative of embryogenesis, its various expressions should be as much like each other as they resemble the development of embryonic appendage buds, which they do. It follows that the uneven distribution of regeneration must have been due to its extinction here and there, not as a negative adaptation by natural selection but as a pleiotropic epiphenomenon linked to more useful adaptations with which it was incompatible. In vertebrate evolution, these adaptations have included the transition from aquatic to terrestrial habitats and the modification of poikilothermic to homeothermic metabolism. The former advance rendered the regeneration of weight-bearing limbs impractical; the latter favored rapid wound healing and scar formation which effectively precluded blastema formation. If the latent capacity for regeneration persists in non-regenerative appendages, as would seem to be the case, then the restoration of its overt expression should be possible if the mechanisms of its inhibition could be discovered and eventually rendered ineffectual.     

The cell: locus or object of inquiry?

Research in many fields of biology has been extremely successful in decomposing biological mechanisms to discover their parts and operations. It often remains a significant challenge for scientists to recompose these mechanisms to understand how they function as wholes and interact with the environments around them. This is true of the eukaryotic cell. Although initially identified in nineteenth-century cell theory as the fundamental unit of organisms, researchers soon learned how to decompose it into its organelles and chemical constituents and have been highly successful in understanding how these carry out many operations important to life. The emphasis on decomposition is particularly evident in modern cell biology, which for the most part has viewed the cell as merely a locus of the mechanisms responsible for vital phenomena. The cell, however, is also an integrated system and for some explanatory purposes it is essential to recompose it and understand it as an organized whole. I illustrate both the virtues of decomposition (treating the cell as a locus) and recomposition (treating the cell as an object) with recent work on circadian rhythms. Circadian researchers have both identified critical intracellular operations that maintain endogenous oscillations and have also addressed the integration of cells into multicellular systems in which cells constitute units.     

The Elusive Honey Bee Dance “Language” Hypothesis

In the mid-1930s, Karl von Frisch proposed the equivalent of an odor-search hypothesis for honey bee recruitment to food sources. A decade later he switched to the equivalent of a dance language hypothesis (though he apparently did not consider his conclusions as hypotheses in either case). The later and more exotic hypothesis rapidly gained acceptance, but it failed its first experimental tests in the mid-1960s; searching recruits did not behave as von Frisch indicated they should under the language hypothesis. His earlier and more conservative odor-search hypothesis meshed better with results obtained in those test experiments. Language advocates then ignored basic precepts of scientific process, rejected and/or ignored results not in accord with their favored hypothesis, and instead repeatedly sought additional supportive evidence. While so doing, they inadvertently accumulated yet more evidence counter to von Frisch's original intent. By invoking ad hoc modifications and qualifications, advocates weakened, rather than strengthened, the hypothesis they continued to embrace. That strict adherence to the language hypothesis has had an unfortunate result; the exclusive investment in that line of research by various governmental agencies has failed to provide practical help to beekeepers or growers in the past half-century.     

Sleep Related Breathing Disorders and Inflammation — The Missing Link? A Cohort Study Evaluating the Interaction of Inflammation and Sleep Related Breathing Disorders and Effects of Treatment

Introduction

Sleep related breathing disorders (SRBD) are associated with both obesity and systemic inflammation. While the relationship between obesity and SRBD is established, the causality between inflammation and SRBD remains unclear. In this study we investigated the relation between SRBD and C-reactive protein (CRP) as a parameter of inflammation and the influence of SRBD treatment on CRP with additional regard to changes in metabolic and cardiovascular parameters.

Methods

Polysomnography (PSG) and laboratory data of patients diagnosed with SRBD over a period of 5 years were prospectively collected in a database and retrospectively analysed regarding the association of SRBD (according to apnoea-hypopnoea- index (AHI), duration of events and extent of desaturation) to CRP, blood pressure, cholesterol, fasting plasma glucose, HbA1c, quality of life measured via a visual analogue scale (VAS 0–100%), and the effects of SRBD therapy on these parameters.

Results

716 patients were included in the study, 171 with mild SRBD (AHI ≥5 to <15/h), 209 with moderate SRBD (AHI 15 to <30/h), 336 with severe SRBD (AHI ≥30/h). Results according to severity of SRBD. Severe SRBD was significantly associated with elevated levels of CRP (3.7 [1.8–7.0] mg/l, vs. moderate (p = 0.001), and mild SRBD (p<0.001), and higher prevalence of hypertension as compared to moderate and mild SRBD (p<0.001, respectively). Results in highly successful treatment. If SRBD treatment was highly successful (AHI <5/h), CRP and quality of life improved significantly (p = 0.001 and p = 0.002), as did blood pressure (p<0.001 for systolic and diastolic values), although BMI increased (p<0.001). Results in partially successful treatment. If success was defined as reduction of AHI of ≥50%, CRP also decreased (p<0.001), as did blood pressure (p<0.001). Again, BMI increased (p<0.001).

Conclusion

This is the first study to show an association of SRBD and CRP independently of BMI in a large cohort. The SRBD therapy-induced CRP decrease was not associated with BMI changes or metabolic changes but rather with the magnitude of AHI improvement.