Abstract
The IPD-IMGT/HLA Database, http://www.ebi.ac.uk/ipd/imgt/hla/, currently contains over 25 000 allele sequence for 45 genes, which are located within the Major Histocompatibility Complex ...(MHC) of the human genome. This region is the most polymorphic region of the human genome, and the levels of polymorphism seen exceed most other genes. Some of the genes have several thousand variants and are now termed hyperpolymorphic, rather than just simply polymorphic. The IPD-IMGT/HLA Database has provided a stable, highly accessible, user-friendly repository for this information, providing the scientific and medical community access to the many variant sequences of this gene system, that are critical for the successful outcome of transplantation. The number of currently known variants, and dramatic increase in the number of new variants being identified has necessitated a dedicated resource with custom tools for curation and publication. The challenge for the database is to continue to provide a highly curated database of sequence variants, while supporting the increased number of submissions and complexity of sequences. In order to do this, traditional methods of accessing and presenting data will be challenged, and new methods will need to be utilized to keep pace with new discoveries.
Aortic valve stenosis (AS) is the most prevalent valvular heart disease in developed countries and is associated with the development of severe secondary complications such as aortic dilatation and ...aneurysm. Emerging evidence suggests that the modified hemodynamic environment associated with AS can cause altered flow patterns in the ascending aorta associated with aortic wall remodeling and development of aortopathy. Recent advances in magnetic resonance imaging (MRI) allow for the comprehensive visualization and quantification of in vivo aortic flow pattern dynamics. In particular, the technique of 4-dimensional flow MRI offers the opportunity to derive advanced hemodynamic measures such as vorticity and helicity, wall shear stress, flow displacement, pressure gradients, viscous energy loss, and turbulent kinetic energy. This review introduces 4-dimensional flow MRI for blood flow visualization and quantification of hemodynamic metrics in the setting of aortic valve disease, with a focus on AS and associated secondary aortopathy.
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Current orthodoxy states that coronary heart disease results from the unhealthy lifestyles of westernized adults together with a contribution from genetic inheritance. This does not provide a ...secure basis for prevention of the disease. Geographical studies gave the first clue that the disease originates during intra‐uterine development. Variations in mortality from the disease across England and Wales were shown to correlate closely with past differences in death rates among newborn babies. In the past most deaths among newborns were attributed to low birthweight. This led to the hypothesis that undernutrition in utero permanently changes the body's structure, function and metabolism in ways that lead to coronary heart disease in later life. The association between low birthweight and coronary heart disease has been confirmed in longitudinal studies of men and women around the world. The developmental model of the origins of the disease offers a new way forward.
Summary
The domestic Asian water buffalo (Bubalus bubalis) is found on all five continents, with a global population of some 202 million. The livelihoods of more people depend on this species than on ...any other domestic animal. The two distinct types (river and swamp) descended from different wild Asian water buffalo (Bubalus arnee) populations that diverged some 900 kyr BP and then evolved in separate geographical regions. After domestication in the western region of the Indian subcontinent (ca. 6300 years BP), the river buffalo spread west as far as Egypt, the Balkans and Italy. Conversely, after domestication in the China/Indochina border region ca. 3000–7000 years BP, swamp buffaloes dispersed through south‐east Asia and China as far as the Yangtze River valley. Molecular and morphological evidence indicates that swamp buffalo populations have strong geographic genetic differentiation and a lack of gene flow, but strong phenotypic uniformity. In contrast, river buffalo populations show a weaker phylogeographic structure, but higher phenotypic diversity (i.e. many breeds). The recent availability of a high‐quality reference genome and of a medium‐density marker panel for genotyping has triggered a number of genome‐wide investigations on diversity, evolutionary history, production traits and functional elements. The growing molecular knowledge combined with breeding programmes should pave the way to improvements in production, environmental adaptation and disease resistance in water buffalo populations worldwide.
Prion-like propagation of tau aggregation might underlie the stereotyped progression of neurodegenerative tauopathies. True prions stably maintain unique conformations (“strains”) in vivo that link ...structure to patterns of pathology. We now find that tau meets this criterion. Stably expressed tau repeat domain indefinitely propagates distinct amyloid conformations in a clonal fashion in culture. Reintroduction of tau from these lines into naive cells reestablishes identical clones. We produced two strains in vitro that induce distinct pathologies in vivo as determined by successive inoculations into three generations of transgenic mice. Immunopurified tau from these mice recreates the original strains in culture. We used the cell system to isolate tau strains from 29 patients with 5 different tauopathies, finding that different diseases are associated with different sets of strains. Tau thus demonstrates essential characteristics of a prion. This might explain the phenotypic diversity of tauopathies and could enable more effective diagnosis and therapy.
•Tau stably propagates multiple amyloid conformations (strains) in dividing cells•Strains induce unique pathologies in transgenic mice•Strains can be passaged through multiple generations of mice and back to cells•Different tauopathies are associated with different sets of strains
Prions stably propagate unique conformations (strains) that produce different pathologies. Sanders et al. now report that tau acts as a prion in cells and in vivo by this criterion and find that different tauopathies are associated with unique tau strains.
The presence of various types of chemical interactions in metal‐halide perovskite semiconductors gives them a characteristic “soft” fluctuating structure, prone to a wide set of defects. ...Understanding of the nature of defects and their photochemistry is summarized, which leverages the cooperative action of density functional theory investigations and accurate experimental design. This knowledge is used to describe how defect activity determines the macroscopic properties of the material and related devices. Finally, a discussion of the open questions provides a path towards achieving an educated prediction of device operation, necessary to engineer reliable devices.
The photochemistry of halide‐related defects affects the optoelectronic properties of lead–halide perovskite semiconductors and their reactivity to external stimuli such as light and environmental molecules.
An animal’s survival depends on its ability to correctly evaluate sensory stimuli and select appropriate behavioral responses. When confronted with ambiguous stimuli, the brain is faced with the task ...of selecting one action while suppressing others. Although conceptually simple, the site and substrate of this elementary form of decision making is still largely unknown. Zebrafish larvae respond to a moving dot stimulus in either of two ways: a small object (potential prey) evokes approach, whereas a large object (potential predator) is avoided. The classification of object size relies on processing in the optic tectum. We genetically identified a population of cells, largely comprised of glutamatergic tectal interneurons with non-stratified morphologies, that are specifically required for approach toward small objects. When these neurons are ablated, we found that the behavioral response is shifted; small objects now tend to elicit avoidance. Conversely, optogenetic facilitation of neuronal responses with channelrhodopsin (ChR2) enhances approaches to small objects. Calcium imaging in head-fixed larvae shows that a large proportion of these neurons are tuned to small sizes. Their receptive fields are shaped by input from retinal ganglion cells (RGCs) that are selective for prey identity. We propose a model in which valence-based decisions arise, at a fundamental level, from competition between dedicated sensorimotor pathways in the tectum.
•Decision between approach versus avoidance of moving objects requires the tectum•Ablation of a subset of interneurons increases avoidance of small moving objects•Optogenetic facilitation of these neurons enhances approach to small moving objects•Interneurons that exhibit narrow size tuning receive input from prey-selective RGCs
Barker and Baier use a visually mediated behavior to investigate sensorimotor decision making in the larval zebrafish. They identity specific interneurons in the optic tectum that bias behavioral choice to approaches. These neurons are tuned to a narrow range of sizes and have receptive fields shaped by prey-selective retinal ganglion cell inputs.
A powerful Fe(III)/NaBH4-mediated free radical hydrofluorination of unactivated alkenes is disclosed using Selectfluor reagent as a source of fluorine and resulting in exclusive Markovnikov addition. ...In contrast to the traditional and unmanageable free radical hydrofluorination of alkenes, the Fe(III)/NaBH4-mediated reaction is conducted under exceptionally mild reaction conditions (0 °C, 5 min, CH3CN/H2O). The reaction can be conducted open to the air and with water as a cosolvent and demonstrates an outstanding substrate scope and functional group tolerance.
Animals use the sense of vision to scan their environment, respond to threats, and locate food sources. The neural computations underlying the selection of a particular behavior, such as escape or ...approach, require flexibility to balance potential costs and benefits for survival. For example, avoiding novel visual objects reduces predation risk but negatively affects foraging success. Zebrafish larvae approach small, moving objects (“prey”) and avoid large, looming objects (“predators”). We found that this binary classification of objects by size is strongly influenced by feeding state. Hunger shifts behavioral decisions from avoidance to approach and recruits additional prey-responsive neurons in the tectum, the main visual processing center. Both behavior and tectal function are modulated by signals from the hypothalamic-pituitary-interrenal axis and the serotonergic system. Our study has revealed a neuroendocrine mechanism that modulates the perception of food and the willingness to take risks in foraging decisions.
•Feeding state influences approach versus avoidance decisions in zebrafish•Hunger alters the neural representation of prey-like stimuli in the tectum•The neuroendocrine and serotonergic systems mediate the modulation by feeding state
Filosa et al. show that hunger enhances the decision by larval zebrafish to approach (versus avoid) moving visual objects and the processing of prey cues in the tectum through signals from the hypothalamic-pituitary-interrenal axis and serotonergic system.
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