How Might DNA Enter the Cohesin Ring?

No abstract available.     

How Might the European Union Engage Constructively with China in the South China Sea?

The decision of the International Court of Justice in the Australia/Japan Whaling Case marks an advance in the law of the sea and the obligation on states to cooperate in common ocean resource regimes. The Court found substantially for Australia, prohibiting Japan's long-running program to capture large cetaceans in the Southern Ocean around Antarctica for scientific research. The Court's discussion of the criteria for states to design and implement scientific research whaling programs is assessed, as is the obligation for cooperation in such research and ocean research generally. The result for whaling and for the future work of the International Whaling Commission is considered.     

How Does the Brain Solve Visual Object Recognition?

Mounting evidence suggests that 'core object recognition,' the ability to rapidly recognize objects despite substantial appearance variation, is solved in the brain via a cascade of reflexive, largely feedforward computations that culminate in a powerful neuronal representation in the inferior temporal cortex. However, the algorithm that produces this solution remains poorly understood. Here we review evidence ranging from?individual neurons and neuronal populations to behavior and computational models. We propose that understanding this algorithm will require using neuronal and psychophysical data to sift through many computational models, each based on building blocks of small, canonical subnetworks with a common functional goal.     

Taurine and Brain Development: Trophic or Cytoprotective Actions?

The decline of taurine content during brain maturation as well as the consequences of taurine deficiency disturbing brain development, suggest its involvement in basic processes of developing brain cells. If taurine participates in cell protection, differentiation or proliferation in the developing brain is as yet unclear. Extensive and solid evidence supports taurine cytoprotective actions, directly or indirectly related to an antioxidant effect. Since redox status and oxidative stress are now implicated in signalling processes regulating cell differentiation and proliferation, the question is raised of whether the taurine antioxidant activity is on the basis of its requirement during brain development.     

Aggregation Modulators Interfere with Membrane Interactions of?β2-Microglobulin Fibrils

Amyloid fibril accumulation is a pathological hallmark of several devastating disorders, including Alzheimer’s disease, prion diseases, type II diabetes, and others. Although the molecular factors responsible for amyloid pathologies have not been deciphered, interactions of misfolded proteins with cell membranes appear to play important roles in these disorders. Despite increasing evidence for the involvement of membranes in amyloid-mediated cytotoxicity, the pursuit for therapeutic strategies has focused on preventing self-assembly of the proteins comprising the amyloid plaques. Here we present an investigation of the impact of fibrillation modulators upon membrane interactions of β₂-microglobulin (β₂m) fibrils. The experiments reveal that polyphenols (epigallocatechin gallate, bromophenol blue, and resveratrol) and glycosaminoglycans (heparin and heparin disaccharide) differentially affect membrane interactions of β₂m fibrils measured by dye-release experiments, fluorescence anisotropy of labeled lipid, and confocal and cryo-electron microscopies. Interestingly, whereas epigallocatechin gallate and heparin prevent membrane damage as judged by these assays, the other compounds tested had little, or no, effect. The results suggest a new dimension to the biological impact of fibrillation modulators that involves interference with membrane interactions of amyloid species, adding to contemporary strategies for combating amyloid diseases that focus on disruption or remodeling of amyloid aggregates.     

Synaptic Pruning in Schizophrenia: Does Minocycline Modulate Psychosocial Brain Development?

Recent studies suggest that the tetracycline antibiotic minocycline, or its cousins, hold therapeutic potential for affective and psychotic disorders. This is proposed on the basis of a direct effect on microglia-mediated frontocortical synaptic pruning (FSP) during adolescence, perhaps in genetically susceptible individuals harboring risk alleles in the complement component cascade that is involved in this normal process of CNS circuit refinement. In reviewing this field, it is argued that minocycline is actually probing and modulating a deeply evolved and intricate system wherein psychosocial stimuli sculpt the circuitry of the “social brain” underlying adult behavior and personality. Furthermore, this system can generate psychiatric morbidity that is not dependent on genetic variation. This view has important ramifications for understanding “pathologies” of human social behavior and cognition as well as providing long-sought potential mechanistic links between social experience and susceptibility to mental and physical disease.     

How to Explore Morphological Integration in Human Evolution and Development?

Most studies in evolutionary developmental biology focus on large-scale evolutionary processes using experimental or molecular approaches, whereas evolutionary quantitative genetics provides mathematical models of the influence of heritable phenotypic variation on the short-term response to natural selection. Studies of morphological integration typically are situated in-between these two styles of explanation. They are based on the consilience of observed phenotypic covariances with qualitative developmental, functional, or evolutionary models. Here we review different forms of integration along with multiple other sources of phenotypic covariances, such as geometric and spatial dependencies among measurements. We discuss one multivariate method [partial least squares analysis (PLS)] to model phenotypic covariances and demonstrate how it can be applied to study developmental integration using two empirical examples. In the first example we use PLS to study integration between the cranial base and the face in human postnatal development. Because the data are longitudinal, we can model both cross-sectional integration and integration of growth itself, i.e., how cross-sectional variance and covariance is actually generated in the course of ontogeny. We find one factor of developmental integration (connecting facial size and the length of the anterior cranial base) that is highly canalized during postnatal development, leading to decreasing cross-sectional variance and covariance. A second factor (overall cranial length to height ratio) is less canalized and leads to increasing (co)variance. In a second example, we examine the evolutionary significance of these patterns by comparing cranial integration in humans to that in chimpanzees.     

How frugal is Mother Nature with haplotypes?

Motivation: Inference of haplotypes from genotype data is crucialand challenging for many vitally important studies. The first,and most critical step, is the ascertainment of a biologicallysound model to be optimized. Many models that have been proposedrely partially or entirely on reducing the number of uniquehaplotypes in the solution. Results: This article examines the parsimony of haplotypes usingknown haplotypes as well as genotypes from the HapMap project.Our study reveals that there are relatively few unique haplotypes,but not always the least possible, for the datasets with knownsolutions. Furthermore, we show that there are frequently verylarge numbers of parsimonious solutions, and the number increasesexponentially with increasing cardinality. Moreover, these solutionsare quite varied, most of which are not consistent with thetrue solutions. These results quantify the limitations of thePure Parsimony model and demonstrate the imperative need toconsider additional properties for haplotype inference models.At a higher level, and with broad applicability, this articleillustrates the power of combinatorial methods to tease outimperfections in a given biological model. Contact: weixiong.zhang{at}wustl.edu Associate Editor: Alex Bateman     

How does doxorubicin interfere with actin polymerization?

It is well known that doxorubicin (adriamycin), an antibiotic with an antitumoral action, has some undesirable side effects. Among these, the most serious is, undoubtedly, damage to myocardial tissue (progressive cardiomyopathy). We have for some time focused our attention on the effect of this drug on cellular contractile systems and, more specifically, on the process of actin polymerization, which we consider to be an extremely delicate key point for the economy of most cellular motor manifestations. In the present study, using capillary viscometry, spectrofluorometry and electron microscopy, we have shown a negative action of doxorubicin on various important chemical events which contribute to the transformation of G-actin into F-actin. Specifically, we found that the drug mainly acts by reducing the polymer size. A possible action mechanism of the antibiotic is proposed and a plausible correlation among the events described in vitro and those observed in vivo is advanced.     

How does Behavior Change the Brain? Multiple Methods to Answer Old Questions

Clearly the brain controls behavior but can behavior also "control" the brain? On an evolutionary time scale, selective ecological pressures shape the sensory and motor capacities as well as the body and behavior. Correspondingly, in development, behavior acts in concert with the environment to cause structural changes in the brain lasting a lifetime. Surprisingly, in "real time" social behavior can also cause changes, typically reversible, in the brain in adult animals. Changes caused by behavioral interactions can be dramatic, and in many instances, these interactions are directly related to reproductive behavior. Understanding how behavior sculpts the brain in the course of behavioral interactions is a major challenge. Analyzing such changes requires a model system allowing control of the biological and behavioral environment of many animals simultaneously yet allowing access to physiological, cellular and molecular processes being regulated. The mouthbrooding cichlid Haplochromis (Astatotilapia) burtoni (Günther) from Lake Tanganyika lends itself to the study of social influences on the brain. It has complex, though easily observable individual and social behaviors regulated by two distinct classes of males, those with territories and those without. Many features of the animals are shaped by social encounters including the maturation of juveniles, the hypothalamic-pituitary-gonadal axis, the growth rate, the basal stress level among others. How does social information effect change in the brain and body? Animals must attend to the social scene to identify their chances. Learning how social information is transduced into cellular changes in this species should help understand how this happens in other social animals.     

Immune-To-Brain Signaling: How Important are the Blood–Brain Barrier-independent Pathways?

A conceptual obstacle for understanding immune-to-brain signaling is the issue of the blood-brain barrier (BBB). In the last 30 years, several pathways have been investigated to address the question of how peripheral immune signals are transmitted into the brain. These pathways can be categorized into two types: BBB-dependent pathways and BBB-independent pathways. BBB-dependent pathways involve the BBB as a relay station or porous barrier, whereas BBB-independent pathways use neuronal routes that bypass the BBB. Recently, a complete BBB-dependent ascending pathway for immune-to-brain signaling has been described. Details of BBB-independent pathways are still under construction. In this review, I will summarize the current progress in unraveling immune-to-brain signaling pathways. In addition, I will provide a critical analysis of the literature to point to areas where our knowledge of the immunological afferent signaling to the central nervous system is still sorely lacking.     

Does Subclinical Hyperthyroidism Predispose to Cocaine Addiction?

ObjectiveTo investigate the relationship between subclinical hyperthyroidism and cocaine abuse.MethodsUsing the computerized patient medical record system at the Veterans Affairs Medical Center in Memphis, Tennessee, we identified the following 3 groups: (1) cocaine abusers without hyperthyroidism; (2) patients with hyperthyroidism without cocaine abuse; and(3) patients with hyperthyroidism and cocaine abuse. In 1,191 patients taken from the same clinic population, we calculated the prevalence of cocaine abuse alone, hyperthyroidism alone, and both diagnoses together to examine whether a relationship existed between hyperthyroidism and cocaine abuse.ResultsWe found the following prevalences: (1) 37.7 per 1,000 patients with cocaine abuse; (2) 18.8 per 1,000 with hyperthyroidism (primarily subclinical); and (3) 65.4 per 1,000 with both hyperthyroidism and cocaine abuse. We found a highly statistically significant correlation between subclinical hyperthyroidism and cocaine abuse (P <<.01 by χ² test) in this population of Veterans Affairs patients. No other significant correlations were found.ConclusionIn our study population, we found a strong correlation between hyperthyroidism (overt or subclinical) and cocaine abuse. Several theoretical mechanisms may explain these findings, but further prospective studies are needed to clarify this complex relationship. (Endocr Pract. 2012;18:478-482)     

Coping with COVID-19 in Sub-Saharan Africa: What Might the Future Hold?

Sub-Saharan countries are sadly linked with similar poor indicators, such as high poverty and mortality rates, the burden of disease, fragile health systems and poorly developed infrastructure. Along with the rest of the world, Sub-Saharan countries are facing this new coronavirus outbreak. Nevertheless, chaotic predictions of a particularly destructive epidemic in Africa do not seem to be borne out, at least for the time being. But uncertainties remain, such as how the virus is spreading in countries with low incomes, informal economies, high HIV/tuberculosis prevalence, extremely low median age, or warm/dry climates and for which containments are almost impossible to enforce? Not even 8 months after the first reported case in China, parts of the world are already showing post-lockdown twilight measures. Yet, the war is certainly far from over, because the virus is gaining ground in the sub-Saharan zone. This viewpoint attempts to describe the COVID-19 crisis in a sub-Saharan perspective, in particular in the Republic of Chad, from both, distant perception and by living it on a daily basis.     

Might there be a medical conscience?

I defend the feasibility of a medical conscience in the following sense: a medical professional can object to the prevailing medical norms because they are incorrect as medical norms. In other words, I provide an account of conscientious objection that makes use of the idea that the conscience can issue true normative claims, but the claims in question are claims about medical norms rather than about general moral norms. I further argue that in order for this line of reasoning to succeed, there needs to be an internal morality of medicine that determines what medical professionals ought to do qua medical professionals. I utilize a constructivist approach to the internal morality of medicine and argue that medical professionals can conscientiously object to providing treatment X, if providing treatment X is not in accordance with norms that would have been constructed, in light of the end of medicine, by the appropriate agents under the appropriate conditions.     

How should we interpret noncompliance with screening mammography?

Primary care practitioners have an important role to play in recommending breast cancer screening to patients in the target age group. In this issue of CMAJ (see pages 1335 to 1343) Dr. Marie-Dominique Beaulieu and associates report the results of a program designed to maximize utilization of screening mammography. Only two thirds of eligible women for whom screening mammography was prescribed obtained a mammogram within the 2-month study period. However, when taken in context, this compliance rate is fairly encouraging. There are many possible reasons for noncompliance such as a need for more information or for repeated suggestions. Family physicians should not become disheartened in their efforts to increase the use of screening procedures and may find that collaboration with others in giving consistent messages will help to maximize screening rates within their patient population.     

How do paedomorphic newts cope with lake drying?

Paedomorphosis, in which adult individuals retain larval traits, is widespread in newts and salamanders. Most evolutionary models predict the maintenance of this life-history trait in favourable aquatic habitats surrounded by hostile terrestrial environments. Nevertheless, numerous ponds inhabited by paedomorphic individuals are unpredictable and temporary. In an experimental framework, I showed that paedomorphic newts were able to metamorphose and thus survive in the absence of water. However, the mere decrease of water level or the life space do not seem to induce metamorphosis in paedomorphs. On the contrary, drying up induces almost all individuals to move on land and after that to colonize other aquatic sites located nearby. Such terrestrial migrations allow survival in drying conditions without metamorphosis as long as the distances of terrestrial migration are short. These results are consistent with the presence of paedomorphs in drying ponds and are in favor of classic optimality models predicting metamorphosis in unfavorable environments.