Are all lyssavirus genes equal for phylogenetic analyses?

Individual lyssavirus genes were evaluated for phylogenetic studies from available full genome sequences. The full genome of the ERA rabies virus was sequenced and its accuracy was confirmed through virus recovery by reverse genetics. The full length of the ERA is 11,931 nucleotides (nt), with a leader sequence of 58 nt, the nucleoprotein (N) gene of 1350 nt, phosphoprotein (P) gene of 891 nt, matrix protein (M) gene of 606 nt, glycoprotein (G) gene of 1572 nt, RNA-dependent RNA polymerase (L) gene of 6384 nt, Psi-region (or G-L intergenic region) of 400 nt, and a trailer region of 70 nt. The five mono-cistrons are separated by intergenic regions of 2, 5, 5 and 24 nt, respectively. One obvious difference between the ERA and SAD-B19 rabies virus strains was the putative stop/polyadenylation signal of the G gene, with a poly(A(8)) tract for ERA, and a poly(A(5)) for SAD-B19. The TGpoly(A(8)) sequence tract was identified to be a leaky termination signal in the ERA strain. Through analyses of nt diversity, protein co-variations, structural and functional constraints, and reconstruction of phylogenetic trees from comprehensive datasets, we propose lyssavirus genes probably are of similar value for phylogenetic analyses.     

A case for immune response genes?

Diabetes is not a single disease. Some patients develop insulin deficiency fairly rapidly and these are usually young, have lymphocytic infiltration of their pancreatic islets, possess circulating islet-cell antibody, and show a strong association with certain HLA phenotypes. This form of the disease is designated type I (juvenile onset or insulin-dependent diabetes mellitus, IDDM). The key factors involved in its pathogenesis were recently reviewed at the fourth of a series of international meetings on the immunology of diabetes'. This meeting was held in memory of Andrew Cudworth whose standing was pre-eminent in the immunogenetics of diabetes and whose untimely death is keenly felt.     

A primitive cell origin for B-cell precursor all?

A stem cell origin has been described for both acute and chronic myelogenous leukemias. In contrast, childhood B-cell precursor acute lymphoblastic leukemia (ALL) is thought to arise in committed B-lineage cells. Recently described in vitro and in vivo model systems that support the proliferation and expansion of ALL cells have provided new tools to investigate the cellular targets for the origin of this malignancy. Evidence suggests that some subtypes of childhood ALL have a primitive cell origin and share many immunophenotypic characteristics with normal progenitor cells. These leukemic stem cells may be resistant to current therapeutic strategies designed to kill the bulk ALL cell population and subsequent relapses may arise from this population. More precise definition of these ALL stem cells through combined analyses of antigen expression, genetic lesions, and functionality is essential for the development of more effective, targeted therapeutic strategies.     

Is the thumb a fifth finger? A study of digit interaction during force production tasks

We studied indices of digit interaction in single- and multi-digit maximal voluntary contraction (MVC) tests when the thumb acted either in parallel or in opposition to the fingers. The peak force produced by the thumb was much higher when the thumb acted in opposition to the fingers and its share of the total force in the five-digit MVC test increased dramatically. The fingers showed relatively similar peak forces and unchanged sharing patterns in the four-finger MVC task when the thumb acted in parallel and in opposition to the fingers. Enslaving during one-digit tasks showed relatively mild differences between the two conditions, while the differences became large when enslaving was quantified for multi-digit tasks. Force deficit was pronounced when the thumb acted in parallel to the fingers; it showed a monotonic increase with the number of explicitly involved digits up to four digits and then a drop when all five digits were involved. Force deficit all but disappeared when the thumb acted in opposition to the fingers. However, for both thumb positions, indices of digit interaction were similar for groups of digits that did or did not include the thumb. These results suggest that, given a certain hand configuration, the central nervous system treats the thumb as a fifth finger. They provide strong support for the hypothesis that indices of digit interaction reflect neural factors, not the peripheral design of the hand. An earlier formal model was able to account for the data when the thumb acted in parallel to the fingers. However, it failed for the data with the thumb acting in opposition to the fingers.     

Ligand recognition during thymic development and γδ T cell function specification

γδ T cells develop in the thymus before entering the periphery. Recent work suggests that thymic development does little to constrain γδ T cell antigen specificities, but instead determines their effector fate. When triggered through the T cell receptor, ligand-naïve γδ T cells produce IL-17, ligand-experienced cells make IFN-γ and those that are strongly self-reactive make IL-4. Importantly, γδ T cells are able to make cytokines immediately upon TCR engagement. These characteristics allow γδ T cells to initiate an acute inflammatory response to pathogens and to host antigens revealed by injury. These advances warrant a fresh look at how γδ T cells may function in the immune system.     

Does cerebral oxygenation affect cognitive function during exercise?

This study tested whether cerebral oxygenation affects cognitive function during exercise. We measured reaction times (RT) of 12 participants while they performed a modified version of the Eriksen flanker task, at rest and while cycling. In the exercise condition, participants performed the cognitive task at rest and while cycling at three workloads [40, 60, and 80% of peak oxygen uptake ( [(V)\dot]\textO ₂ \dot{V}{\text{O}}_{ 2} )]. In the control condition, the workload was fixed at 20 W. RT was divided into premotor and motor components based on surface electromyographic recordings. The premotor component of RT (premotor time) was used to evaluate the effects of acute exercise on cognitive function. Cerebral oxygenation was monitored during the cognitive task over the right frontal cortex using near-infrared spectroscopy. In the exercise condition, we found that premotor time significantly decreased during exercise at 60% peak [(V)\dot]\textO ₂ \dot{V}{\text{O}}_{ 2} relative to rest. However, this improvement was not observed during exercise at 80% peak [(V)\dot]\textO ₂ \dot{V}{\text{O}}_{ 2} . In the control condition, premotor time did not change during exercise. Cerebral oxygenation during exercise at 60% peak [(V)\dot]\textO ₂ \dot{V}{\text{O}}_{ 2} was not significantly different from that at rest, while cerebral oxygenation substantially decreased during exercise at 80% peak [(V)\dot]\textO ₂ \dot{V}{\text{O}}_{ 2} . The present results suggest that an improvement in cognitive function occurs during moderate exercise, independent of cerebral oxygenation.     

Potential roles for tumour necrosis factorα during embryonic development

This paper reviews the evidence indicating possible roles for tumour necrosis factor-alpha (TNF) in development. It is proposed that TNF may have essentially three major roles during embryonic development, which may be analogous to its roles in the immune system and during inflammation: a role in programmed cell death; a role as a cellular growth and differentiation factor; and also a role in the remodelling of extracellular matrix, and the regulation of cell adhesion molecules and integrins. The concept of the existence of a cytokine array during embryogenesis, analogous to that occurring in inflammation, is discussed, as well as potential roles for TNF in the induction of ubiquitin; protective mechanisms embryonic cells may employ against TNF-mediated cytotoxicity; and a consideration of the role TNF may play in a free radical theory of development.     

Breathing during cardiac arrest following exercise: A new function of the respiratory system?

We have found in four sheep that, following a muscular exercise, minute ventilation is maintained for 34-131 s during a cardiac arrest (CA), at a magnitude (from 28.2 and 54.7 l min(-1)) similar to the level of ventilation (and thus proportional to the metabolic rate) preceding the period of asystole. Breathing was maintained despite the lack of pulmonary blood flow and the cessation of the muscle contractions, leading to a dramatic reduction in alveolar FCO(2) (1.9 ± 1%). Secondly, swings in arterial blood pressure (ABP) were observed (pulse pressure of 31 ± 3 Torr) in phase with breathing movements in place of the cardiac activity. This "protective" response, deprived from any role in blood gas homeostasis, as circulation is virtually abolished, is not predictable from the traditional respiratory control feedback systems thought to be involved in exercise. We are presenting the view that this response, dissociated from the pulmonary gas exchanges, is the expression of a rudimentary defense mechanism aimed at limiting the consequences of an acute failure of the cardiac pump by the thoraco-abdominal pump.     

Genetic horoscopes: is it all in the genes? Points for regulatory control of direct-to-consumer genetic testing

The development of tests for genetic susceptibility to common complex diseases has raised concerns. These concerns relate to evaluation of the scientific and clinical validity and utility of the tests, quality assurance of laboratories and testing services, advice and protection for the consumer and the appropriate regulatory and policy response. How these concerns are interpreted and addressed is an ongoing debate. If the possibility of using the discoveries from genomic science to improve health is to be realised without losing public confidence, then improvements in the evaluation and mechanisms for control of supply of tests may be as important as the science itself.     

Thromboprophylaxis in medical patients--why not for all?

Venous thromboembolism (VTE) is a major problem in non-surgical patients admitted to the hospital, both during the hospitalization period and after discharge. Risk factors for VTE are well known and scoring systems have been published. Nevertheless, prophylaxis against VTE is in many hospitals used less often than ideal and also inappropriately. Electronic tools to alert the physicians to provide prophylaxis and suggest suitable measures have shown promising results with a reduction of clinically relevant VTE. Large randomized clinical trials have demonstrated efficacy of low molecular-weight heparin (LMWH), pentasaccharide(fondaparinux) and unfractionated heparin. The results were, however, driven by asymptomatic deep vein thrombosis (DVT), including distal DVT in some studies. A reduction of pulmonary embolism is achieved, but without any significant effect on the mortality. The agents are generally safe, with only a small increase of major bleeding, less with LMWH than with unfractionated heparin. The challenge is still to direct the efforts to the most appropriate patients.     

Are cortisol profiles a stable trait during child development?

Exposure to stressful experiences can increase vulnerability to adverse health outcomes. A potential neuroendocrine mechanism mediating the link between stress and health is the hypothalamic‐pituitary‐adrenal (HPA) system, with a key role attributed to the glucocorticoid hormone cortisol. Retrospective and cross sectional clinical studies of humans and experimental studies with nonhuman primates and rodents suggest that traumatic experiences during critical periods in development may have permanent effects on HPA regulation, which in turn can have deleterious effects on health. Here I report results from a continuous 20‐year study (1988–2009) of children in a rural community on Dominica. Sequential data on cortisol levels, social stressors, and health in naturalistic, everyday conditions are examined to assess developmental trajectories of HPA functioning. Saliva aliquots were assayed for cortisol in concert with monitoring of growth, morbidity, and social environment. Analyses here include data from 1989 to 1999 for 147 children aged 3–16 years with >100 saliva samples each. Cortisol values were standardized by elapsed time since wake‐up. Results do not support the hypothesis that traumatic stress during childhood causes permanent general elevation of cortisol levels. Am. J. Hum. Biol., 2009. © 2009 Wiley‐Liss, Inc.     

A role for both HLA-F and HLA-G in reproduction and during pregnancy?

The human major histocompatibility complex includes a group of non-classical HLA class I genes, HLA-E, -F and -G. While nearly all focus since the discovery of these class Ib molecules have been on basic biochemistry and molecular biology of HLA-G and HLA-E, as well as their expression patterns, functions in immune modulation and during pregnancy, and also possible implications in a range of diseases, in infertility and pregnancy complications, HLA-F has nearly been ignored. However, recent discoveries show that HLA-F can be expressed as both open conformers binding to a number of KIRs on primarily NK cells, as well as peptide-bound HLA-F binding to ILT2 and ILT4. Furthermore, a number of reports indicate a possible involvement of HLA-F in viral infections, in cancer immunology, and in fertility and reproduction, which may initiate more interest in this rather unknown HLA class I molecule. In this short review, we focus on recent discoveries that indicate a functional role for HLA-F in reproduction and during pregnancy, and the role of HLA-F in relation to HLA-G.