Understanding the role of wild ruminants in anthelmintic resistance in livestock

Wild ruminants are susceptible to infection from generalist helminth species, which can also infect domestic ruminants. A better understanding is required of the conditions under which wild ruminants can act as a source of helminths (including anthelmintic-resistant genotypes) for domestic ruminants, and vice versa, with the added possibility that wildlife could act as refugia for drug-susceptible genotypes and hence buffer the spread and development of resistance. Helminth infections cause significant productivity losses in domestic ruminants and a growing resistance to all classes of anthelmintic drug escalates concerns around helminth infection in the livestock industry. Previous research demonstrates that drug-resistant strains of the pathogenic nematode Haemonchus contortus can be transmitted between wild and domestic ruminants, and that gastro-intestinal nematode infections are more intense in wild ruminants within areas of high livestock density. In this article, the factors likely to influence the role of wild ruminants in helminth infections and anthelmintic resistance in livestock are considered, including host population movement across heterogeneous landscapes, and the effects of climate and environment on parasite dynamics. Methods of predicting and validating suspected drivers of helminth transmission in this context are considered based on advances in predictive modelling and molecular tools.     

Notch3 expression in capillary pericytes predicts worse graft outcome in human renal grafts with antibody‐mediated rejection

Microvasculature consisting of endothelial cells and pericytes is the main site of injury during antibody‐mediated rejection (ABMR) of renal grafts. Little is known about the mechanisms of activation of pericytes in this pathology. We have found recently that activation of Notch3, a mediator of vascular smooth muscle cell proliferation and dedifferentiation, promotes renal inflammation and fibrosis and aggravates progression of renal disease. Therefore, we studied the pericyte expression of Notch3 in 49 non‐selected renal graft biopsies (32 for clinical cause, 17 for graft surveillance). We analysed its relationship with patients’ clinical and morphological data, and compared with the expression of partial endothelial mesenchymal transition (pEndMT) markers, known to reflect endothelial activation during ABMR. Notch3 was de novo expressed in pericytes of grafts with ABMR, and was significantly correlated with the microcirculation inflammation scores of peritubular capillaritis and glomerulitis and with the expression of pEndMT markers. Notch3 expression was also associated with graft dysfunction and proteinuria at the time of biopsy and in the long term. Multivariate analysis confirmed pericyte expression of Notch3 as an independent risk factor predicting graft loss. These data suggest that Notch3 is activated in the pericytes of renal grafts with ABMR and is associated with poor graft outcome.     

Wealth transmission and inequality among hunter-gatherers

We report quantitative estimates of intergenerational transmission and population-wide inequality for wealth measures in a set of hunter-gatherer populations. Wealth is defined broadly as factors that contribute to individual or household well-being, ranging from embodied forms such as weight and hunting success to material forms such household goods, as well as relational wealth in exchange partners. Intergenerational wealth transmission is low to moderate in these populations, but is still expected to have measurable influence on an individual's life chances. Wealth inequality (measured with Gini coefficients) is moderate for most wealth types, matching what qualitative ethnographic research has generally indicated (if not the stereotype of hunter-gatherers as extreme egalitarians). We discuss some plausible mechanisms for these patterns, and suggest ways in which future research could resolve questions about the role of wealth in hunter-gatherer social and economic life.     

Cortical hypercolumn size determines stereo fusion limits

The size of a pair of cortical ocular dominance columns determines a basic anatomical module of V-1 which Hubel and Wiesel have termed the hypercolumn. Does this correspond to a basic functional, or psychophysically measurable, module as well? This is the basic question addressed in the present paper. Since the ocular dominance column architecture is presumed to be related to stereo vision, it is natural to assume that hypercolumn size should provide a modular basis for basic phenomena of stereopsis. In previous work, we have suggested that local nonlinear filtering via the cepstral transform, operating on a local window of cortical tissue scaled by hypercolumn size, provides such a modular model of stereopsis. In the present paper, we review this model and then discuss a number of issues related to the biological plausibility and implementation of this algorithm. Then, we present the main result of this paper: we have analyzed a number of experiments related to stereo fusion limits (Panum's area) and to disparity gradient and disparity scaling, and demonstrate that there is a simple unifying explanation for these phenomena in terms of a constant cortical module whose size is determined by a pair of ocular dominance columns. As a corollary, Panum's area must increase according to (inverse) cortical magnification factor. We show that this is supported by all existing experimental data.     

Systems biology and its potential role in radiobiology

About a century ago, Conrad Röentgen discovered X-rays, and Henri Becquerel discovered a new phenomenon, which Marie and Pierre Curie later coined as radio-activity. Since their seminal work, we have learned much about the physical properties of radiation and its effects on living matter. Alas, the more we discover, the more we appreciate the complexity of the biological processes that are triggered by radiation exposure and eventually lead (or do not lead) to disease. Equipped with modern biological methods of high-throughput experimentation, imaging, and vastly increased computational prowess, we are now entering an era where we can piece some of the multifold aspects of radiation exposure and its sequelae together, and develop a more systemic understanding of radiogenic effects such as radio-carcinogenesis than has been possible in the past. It is evident from the complexity of even the known processes that such an understanding can only be gained if it is supported by mathematical models. At this point, the construction of comprehensive models is hampered both by technical inadequacies and a paucity of appropriate data. Nonetheless, some initial steps have been taken already and the generally increased interest in systems biology may be expected to speed up future progress. In this context, we discuss in this article examples of relatively small, yet very useful models that elucidate selected aspects of the effects of exposure to ionizing radiation and may shine a light on the path before us.     

Preparation of pure populations of covalently stabilized amyloid β-protein oligomers of specific sizes

Evidence suggests that amyloid β-protein (Aβ) oligomers may be seminal pathogenic agents in Alzheimer's disease (AD). If so, developing oligomer-targeted therapeutics requires an understanding of oligomer structure. This has been difficult due to the instability of these non-covalently associated Aβ assemblies. We previously used rapid, zero-length, in situ chemical cross-linking to stabilize oligomers of Aβ40. These enabled us to isolate pure, stable populations of dimers, trimers, and tetramers and to determine their structure-activity relationships. However, equivalent methods applied to Aβ42 did not produce stable oligomers. We report here that the use of an Aβ42 homologue, [F10, Y42]Aβ42, coupled with sequential denaturation/dissociation and gel electrophoresis procedures, provides the means to produce highly pure, stable populations of oligomers of sizes ranging from dimer through dodecamer that are suitable for structure-activity relationship determination.     

Species pairs of north temperate freshwater fishes: Evolution,taxonomy, and conservation

Many fish species contain morphologically, ecologically and geneticallydistinct populations that are sympatric during at least some portion oftheir life cycle. Such reproductively isolated populations act asdistinct biological species, but are identified by a common Latinbinomial. These species pairs are particularly common in freshwaterfish families such as Salmonidae, Gasterosteidae and Osmeridae and aretypically associated with postglacial lakes in north temperateenvironments. The nature of the divergences between sympatric species,factors contributing to reproductive isolation, and modes of evolutionare reviewed with particular emphasis on benthic and limnetic pairs ofthreespine sticklebacks, Gasterosteus aculeatus, and anadromous(sockeye salmon) and nonanadromous (kokanee) pairs of Oncorhynchusnerka. Phylogenetic analyses typically indicate that divergencesbetween members of replicate pairs have occurred independently and,hence, particular phenotypes are not monophyletic. Consequently,taxonomic resolution of such species complexes is a vexing problem foradherents to our traditional Linnaean classification system. Sympatricspecies pairs represent a significant component of the biodiversity oftemperate freshwater ecosystems which may be underestimated because oursystem of formal taxonomy tends to obscure diversity encompassed byspecies pairs. Conservation of such systems should be recognized as apriority without formal taxonomic designation of members of speciespairs because taxonomic resolution will likely continue to proveextremely difficult when employing traditional hierarchies andprocedures.