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Memory for isolated absolute pitches is extremely rare in Western, English-speaking populations. However, past research has found that people can voluntarily reproduce well-known songs in the original key much more often than chance. It is unknown whether this requires deliberate effort or if it manifests in involuntary musical imagery (INMI, or earworms). Participants (N = 30, convenience sample) were surveyed at random times over a week and asked to produce a sung recording of any music they were experiencing in their heads. We measured the "pitch error" of each recording to the nearest semitone by comparing participants' recordings to the original song. We found that 44.7% of recordings had a pitch error of 0 semitones, and 68.9% of recordings were within ± 1 semitone of the original song. Our results provide novel evidence that a large proportion of the population has access to absolute pitch, as revealed in their INMI. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) quantification of intramuscular fat accumulation is a responsive biomarker in neuromuscular diseases. Despite emergence of automated methods, manual muscle segmentation remains an essential foundation. We aimed to develop a training programme for new observers to demonstrate competence in lower limb muscle segmentation and establish reliability benchmarks for future human observers and machine learning segmentation packages. Methods: The learning phase of the training programme comprised a training manual, direct instruction, and eight lower limb MRI scans with reference standard large and small regions of interest (ROIs). The assessment phase used test–retest scans from two patients and two healthy controls. Interscan and interobserver reliability metrics were calculated to identify underperforming outliers and to determine competency benchmarks. Results: Three experienced observers undertook the assessment phase, whilst eight new observers completed the full training programme. Two of the new observers were identified as underperforming outliers, relating to variation in size or consistency of segmentations; six had interscan and interobserver reliability equivalent to those of experienced observers. The calculated benchmark for the Sørensen-Dice similarity coefficient between observers was greater than 0.87 and 0.92 for individual thigh and calf muscles, respectively. Interscan and interobserver reliability were significantly higher for large than small ROIs (all p < 0.001). Conclusions: We developed, implemented, and analysed the first formal training programme for manual lower limb muscle segmentation. Large ROI showed superior reliability to small ROI for fat fraction assessment. Relevance statement: Observers competent in lower limb muscle segmentation are critical to application of quantitative muscle MRI biomarkers in neuromuscular diseases. This study has established competency benchmarks for future human observers or automated segmentation methods. Key points: • Observers competent in muscle segmentation are critical for quantitative muscle MRI biomarkers. • A training programme for muscle segmentation was undertaken by eight new observers. • We established competency benchmarks for future human observers or automated segmentation methods. [ABSTRACT FROM AUTHOR]

Zika and dengue virus nonstructural protein 5 antagonism of STAT2, a critical interferon signaling transcription factor, to suppress the host interferon response is required for viremia and pathogenesis in a vertebrate host. This affects viral species tropism, as mouse STAT2 resistance renders only immunocompromised or humanized STAT2 mice infectable. Here, we explore how STAT2 evolution impacts antagonism. By measuring the susceptibility of 38 diverse STAT2 proteins, we demonstrate that resistance arose numerous times in mammalian evolution. In four species, resistance requires distinct sets of multiple amino acid changes that often individually disrupt STAT2 signaling. This reflects an evolutionary ridge where progressive resistance is balanced by the need to maintain STAT2 function. Furthermore, resistance may come with a fitness cost, as resistance that arose early in lemur evolution was subsequently lost in some lemur lineages. These findings underscore that while it is possible to evolve resistance to antagonism, complex evolutionary trajectories are required to avoid detrimental host fitness consequences. Zika and Dengue virus non-structural protein 5 can antagonise STAT2 modulating the host response and this interaction is involved in determining tropism. Here the authors show mammals independently evolved resistance to flavivirus NS5 multiple times, involving complex genetic changes in STAT2 which balance viral defence whilst maintaining STAT2's critical functions. [ABSTRACT FROM AUTHOR]

The Open Databases Integration for Materials Design (OPTIMADE) consortium has designed a universal application programming interface (API) to make materials databases accessible and interoperable. We outline the first stable release of the specification, v1.0, which is already supported by many leading databases and several software packages. We illustrate the advantages of the OPTIMADE API through worked examples on each of the public materials databases that support the full API specification. [ABSTRACT FROM AUTHOR]

Gametophytic cross-incompatibility systems in corn have been the subject of genetic studies for more than a century. They have tremendous economic potential as a genetic mechanism for controlling fertilization without controlling pollination. Three major genetically distinct and functionally equivalent cross-incompatibility systems exist in Zea mays: Ga1, Tcb1, and Ga2. All three confer reproductive isolation between maize or teosinte varieties with different haplotypes at any one locus. These loci confer genetically separable functions to the silk and pollen: a female function that allows the silk to block fertilization by non-self-type pollen and a male function that overcomes the block of the female function from the same locus. Identification of some of these genes has shed light on the reproductive isolation they confer. The identification of both male and female factors as pectin methylesterases reveals the importance of pectin methylesterase activity in controlling the decision between pollen acceptance versus rejection, possibly by regulating the degree of methylesterification of the pollen tube cell wall. The appropriate level and spatial distribution of pectin methylesterification is critical for pollen tube growth and is affected by both pectin methylesterases and pectin methylesterase inhibitors. We present a molecular model that explains how cross-incompatibility systems may function that can be tested in Zea and uncharacterized cross-incompatibility systems. Molecular characterization of these loci in conjunction with further refinement of the underlying molecular and cellular mechanisms will allow researchers to bring new and powerful tools to bear on understanding reproductive isolation in Zea mays and related species. [ABSTRACT FROM AUTHOR]

Marine phytoplankton have a crucial role in the modulation of marine-based food webs1, fishery yields2 and the global drawdown of atmospheric carbon dioxide3. However, owing to sparse measurements before satellite monitoring in the twenty-first century, the long-term response of planktonic stocks to climate forcing is unknown. Here, using a continuous, multi-century record of subarctic Atlantic marine productivity, we show that a marked 10 ± 7% decline in net primary productivity has occurred across this highly productive ocean basin over the past two centuries. We support this conclusion by the application of a marine-productivity proxy, established using the signal of the planktonic-derived aerosol methanesulfonic acid, which is commonly identified across an array of Greenlandic ice cores. Using contemporaneous satellite-era observations, we demonstrate the use of this signal as a robust and high-resolution proxy for past variations in spatially integrated marine productivity. We show that the initiation of declining subarctic Atlantic productivity broadly coincides with the onset of Arctic surface warming4, and that productivity strongly covaries with regional sea-surface temperatures and basin-wide gyre circulation strength over recent decades. Taken together, our results suggest that the decline in industrial-era productivity may be evidence of the predicted5 collapse of northern Atlantic planktonic stocks in response to a weakened Atlantic Meridional Overturning Circulation6–8. Continued weakening of this Atlantic Meridional Overturning Circulation, as projected for the twenty-first century9,10, may therefore result in further productivity declines across this globally relevant region. A continuous, multi-century record of subarctic Atlantic marine productivity shows that a marked decline in net primary productivity has occurred across the subarctic Atlantic basin over the past two centuries. [ABSTRACT FROM AUTHOR]

Purpose: Clinical shoulder science lacks a benchmark against which the early clinical value of new glenoid components can be compared; such a benchmark may be derived from a multicenter study of patients receiving an established, internationally used design of glenoid component.Methods: We obtained data from 11 centers on 1270 patients having total shoulder arthroplasty using an all-polyethylene component with a fluted central peg. We analyzed individual patient outcomes at 1 and 2 years after surgery. We compared the improvement for each patient to the minimal clinically important difference (MCID) and calculated each patient's improvement as a percent of maximal possible improvement (MPI).Results: The preoperative scores improved from SST 3 ± 2, ASES 37 ± 15, Constant score 36 ± 16, and Penn score 30 ± 19 to SST 10 ± 2, ASES 90 ± 12, Constant 76 ± 13, and Penn 80 ± 24 (p < 0.001 for each). A high percentage of patients improved by more than the MCID (SST 96%, ASES 98%, Constant 94%, Penn 93%) and obtained improvement of at least 30% of the MPI (SST 95%, ASES 98%, Constant 91%, Penn 87%). The clinical outcomes realized with this glenoid design were not worse for the 41% of shoulders with preoperative type B glenoids or for the 30% of shoulders with more than 15 degrees of glenoid retroversion.Conclusions: Individual patients from 11 international practices having total shoulder arthroplasty using a basic glenoid component design obtained highly significant clinical outcomes, providing a benchmark against which the early outcomes of new designs can be compared to determine whether they provide increased clinical value. [ABSTRACT FROM AUTHOR]

The Greenland ice sheet (GrIS) is a growing contributor to global sea-level rise1, with recent ice mass loss dominated by surface meltwater runoff2,3. Satellite observations reveal positive trends in GrIS surface melt extent4, but melt variability, intensity and runoff remain uncertain before the satellite era. Here we present the first continuous, multi-century and observationally constrained record of GrIS surface melt intensity and runoff, revealing that the magnitude of recent GrIS melting is exceptional over at least the last 350 years. We develop this record through stratigraphic analysis of central west Greenland ice cores, and demonstrate that measurements of refrozen melt layers in percolation zone ice cores can be used to quantifiably, and reproducibly, reconstruct past melt rates. We show significant (P < 0.01) and spatially extensive correlations between these ice-core-derived melt records and modelled melt rates5,6 and satellite-derived melt duration4 across Greenland more broadly, enabling the reconstruction of past ice-sheet-scale surface melt intensity and runoff. We find that the initiation of increases in GrIS melting closely follow the onset of industrial-era Arctic warming in the mid-1800s, but that the magnitude of GrIS melting has only recently emerged beyond the range of natural variability. Owing to a nonlinear response of surface melting to increasing summer air temperatures, continued atmospheric warming will lead to rapid increases in GrIS runoff and sea-level contributions. Ice-core-derived melt records reveal that atmospheric warming has recently intensified Greenland ice-sheet surface melt and runoff to levels that are exceptional over at least the last 350 years. [ABSTRACT FROM AUTHOR]

Disease control strategies can have both intended and unintended effects on the dynamics of infectious diseases. Routine testing for the harmful pathogen Bovine Tuberculosis (bTB) was suspended briefly during the foot and mouth disease epidemic of 2001 in Great Britain. Here we utilize bTB incidence data and mathematical models to demonstrate how a lapse in management can alter epidemiological parameters, including the rate of new infections and duration of infection cycles. Testing interruption shifted the dynamics from annual to 4-year cycles, and created long-lasting shifts in the spatial synchrony of new infections among regions of Great Britain. After annual testing was introduced in some GB regions, new infections have become more de-synchronised, a result also confirmed by a stochastic model. These results demonstrate that abrupt events can synchronise disease dynamics and that changes in the epidemiological parameters can lead to chaotic patterns, which are hard to be quantified, predicted, and controlled. [ABSTRACT FROM AUTHOR]

Phenotypic differentiation is common among populations that have large geographic distributions. One proposed mechanism driving phenotype divergence is sexual selection, which predicts that trait differences among closely related populations are underlain by variation in reproductive performance. Here, we examined a population of Asian Barn Swallows (Hirundo rustica gutturalis) in northeastern China. We ask whether traits shown to be under divergent sexual selection in other Barn Swallow populations are under sexual selection in this north Asian population by determining whether two features of phenotype variation, tail streamer length and ventral plumage colouration (including both throat and belly regions), are sexually dimorphic, associated with patterns of assortative mating and predictive of reproductive success. In this population, the length of tail streamers did not correlate with ventral plumage colouration in either males or females. The length of tail streamers was sexually dimorphic, but we did not find assortative mating by tail streamer length. By contrast, we found no sexual dichromatism but we did find assortative mating by throat colouration. Our correlational results indicated that the breeding performance of male Barn Swallows was associated with differences in their ventral plumage colouration, suggesting that ventral plumage colouration is likely a target of sexual selection in this population. Our finding that tail streamer length is unlikely to be under sexual selection is consistent with studies of other H. rustica gutturalis populations. The result that ventral plumage colour is likely to be under sexual selection is partially consistent with previous studies on Japanese H. rustica gutturalis, in which male throat but not belly plumage colour is the sexually selected trait. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis (TB) poses a serious threat for agricultural industry in several countries, it involves potential interactions between wildlife and cattle and creates societal problems in terms of human-wildlife conflict. This study addresses connectedness network analysis, the spatial, and temporal dynamics of TB between cattle in farms and the European badger ( Meles meles) using a large dataset generated by a calibrated agent based model. Results showed that infected network connectedness was lower in badgers than in cattle. The contribution of an infected individual to the mean distance of disease spread over time was considerably lower for badger than cattle; badgers mainly spread the disease locally while cattle infected both locally and across longer distances. The majority of badger-induced infections occurred when individual badgers leave their home sett, and this was positively correlated with badger population growth rates. Point pattern analysis indicated aggregation in the spatial pattern of TB prevalence in badger setts across all scales. The spatial distribution of farms that were not TB free was aggregated at different scales than the spatial distribution of infected badgers and became random at larger scales. The spatial cross correlation between infected badger setts and infected farms revealed that generally infected setts and farms do not coexist except at few scales. Temporal autocorrelation detected a two year infection cycle for badgers, while there was both within the year and longer cycles for infected cattle. Temporal cross correlation indicated that infection cycles in badgers and cattle are negatively correlated. The implications of these results for understanding the dynamics of the disease are discussed. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis (TB) is a chronic disease in cattle that causes a serious food security challenge to the agricultural industry in terms of dairy and meat production. Spatio-temporal disease analysis in terms of time trends and geographic disparities of disease dynamics can provide useful insights into the overall efficiency of control efforts as well as the relative efficiency of different management measures towards eradication. In GB, Scotland has had a risk based surveillance testing policy under which high risk herds are tested frequently, and in September 2009 was officially declared as TB free. Wales have had an annual or more frequent testing policy for all cattle herds since January 2010, while in England several herds are still tested every 4 years except some high TB prevalence areas where annual testing is applied. Time series analysis using publicly available data for total tests on herds, total cattle slaughtered, new herd incidents, and herds not TB free, were analysed globally for GB and locally for the constituent regions of Wales, Scotland, West, North, and East England. After detecting trends over time, underlying regional differences were compared with the testing policies in the region. Total cattle slaughtered are decreasing in Wales, Scotland and West England, but increasing in the North and East English regions. New herd incidents, i.e., disease incidence, are decreasing in Wales, Scotland, West English region, but increasing in North and East English regions. Herds not TB free, i.e., disease prevalence, are increasing in West, North, and East English regions, while they are decreasing in Wales and Scotland. Total cattle slaughtered were positively correlated with total tests in the West, North, and East English regions, with high slopes of regression indicating that additional testing is likely to facilitate the eradication of the disease. There was no correlation between total cattle slaughtered and total tests on herds in Wales indicating that herds are tested frequent enough in order to detect all likely cases and so control TB. The main conclusion of the analysis conducted here is that more frequent testing is leading to lower TB infections in cattle both in terms of TB prevalence as well as TB incidence. [ABSTRACT FROM AUTHOR]

Bovine Tuberculosis (TB) is a major problem for the agricultural industry in several countries. TB can be contracted and spread by species other than cattle and this can cause a problem for disease control. In the UK and Ireland, badgers are a recognised reservoir of infection and there has been substantial discussion about potential control strategies. We present a coupling of individual based models of bovine TB in badgers and cattle, which aims to capture the key details of the natural history of the disease and of both species at approximately county scale. The model is spatially explicit it follows a very large number of cattle and badgers on a different grid size for each species and includes also winter housing. We show that the model can replicate the reported dynamics of both cattle and badger populations as well as the increasing prevalence of the disease in cattle. Parameter space used as input in simulations was swept out using Latin hypercube sampling and sensitivity analysis to model outputs was conducted using mixed effect models. By exploring a large and computationally intensive parameter space we show that of the available control strategies it is the frequency of TB testing and whether or not winter housing is practised that have the most significant effects on the number of infected cattle, with the effect of winter housing becoming stronger as farm size increases. Whether badgers were culled or not explained about 5 %, while the accuracy of the test employed to detect infected cattle explained less than 3 % of the variance in the number of infected cattle. [ABSTRACT FROM AUTHOR]

Three genetic systems conferring cross-incompatibility have been described in Zea mays: Teosinte crossing barrier1- strong ( Tcb1- s) found in teosinte, and Gametophyte factor1- strong ( Ga1- s) and Ga2- s found in maize and teosinte. The reproductive barrier between maize and some weedy teosintes is controlled by the Tcb1- s locus. Multi-generation inheritance experiments on two independent Tcb1- s lineages show that the Tcb1- s barrier is unstable in some maize lines. Reciprocal crosses between Tcb1- s tester plants and three recombinants in the Tcb1- s mapping region demonstrate that the Tcb1- s haplotype contains separable male and female components. In vivo assays of the dynamics of pollen tube growth and pollen tube morphology during rejection of incompatible pollen in silks carrying the Tcb1- s, Ga1- s, or Ga2- s barriers showed that, in all three, pollen tube growth is slower than in compatible crosses at early stages and had ceased by 24 h after pollination. In all three crossing barrier systems, incompatible pollen tubes have clustered callose plugs in contrast to pollen tubes of compatible crosses. Incompatible pollen tubes growing in the Tcb1- s, Ga1- s, and Ga2- s silks have different morphologies: straight, curved, and kinked, respectively. The distinct morphologies suggest that these crossing barriers block incompatible pollen through different mechanisms. This study lays the foundation for cloning the Tcb1 genes and provides clues about the cellular mechanisms involved in pollen rejection in the Tcb1- s, Ga1- s, and Ga2- s crossing barriers. [ABSTRACT FROM AUTHOR]

Peripheral nerve disorders have been a Cinderella subspecialty for neurologists because of the limited treatment options and difficulties in obtaining a genetic diagnosis. In the last decade, there has been great progress in the management of patients with peripheral nerve disease. In this paper, we review a selection of diagnostic and therapeutic papers in this area published in the Journal of Neurology over the last 24 months. [ABSTRACT FROM AUTHOR]

One of the most important measures of offspring performance is growth rate, which is often traded off against another important survival trait, immune function. A particular feature of ostrich chicks maintained in farmed environments is that cohorts of chicks vary widely in size. As parents can have a profound effect on the phenotype and fitness of their offspring, we investigated whether chick growth and immune defence were related to variation in levels of immune defence in their genetic parents. As secondary sexual traits of sires could serve as indicators of male quality, and be used in female mating decisions, we also investigated whether chick growth rate and immune defence were related to male plumage and integumentary colouration. We found that offspring growth rates and humoral responses were related to the humoral responses of their parents, suggesting that at least some components of humoral immune capacity are heritable. The white colour of male ostrich feathers was correlated to the humoral response and growth rate of their offspring, suggesting that this visual cue involved in the male courtship display could serve as an important signal to females of male quality, thereby forming the basis of mate choice in this species. [ABSTRACT FROM AUTHOR]

We introduce two large-scale resources for functional analysis of microRNA (miRNA): a decoy library for inhibiting miRNA function and a sensor library for monitoring microRNA activity. To take advantage of the sensor library, we developed a high-throughput assay called Sensor-seq to simultaneously quantify the activity of hundreds of miRNAs. Using this approach, we show that only the most abundant miRNAs in a cell mediate target suppression. Over 60% of detected miRNAs had no discernible activity, which indicated that the functional 'miRNome' of a cell is considerably smaller than currently inferred from profiling studies. Moreover, some highly expressed miRNAs exhibited relatively weak activity, which in some cases correlated with a high target-to-miRNA ratio or increased nuclear localization of the miRNA. Finally, we show that the miRNA decoy library can be used for pooled loss-of-function studies. These tools are valuable resources for studying miRNA biology and for miRNA-based therapeutics. [ABSTRACT FROM AUTHOR]

Objective: To assess the relationship between MRI-derived changes in whole-brain and ventricular volume with change in cognitive scores in Alzheimer's disease (AD), mild cognitive impairment (MCI) and control subjects.Material and Methods: In total 131 control, 231 MCI and 99 AD subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort with T1-weighted volumetric MRIs from baseline and 12-month follow-up were used to derive volume changes. Mini mental state examination (MMSE), Alzheimer's disease assessment scale (ADAS)-cog and trails test changes were calculated over the same period.Results: Brain atrophy rates and ventricular enlargement differed between subject groups (p < 0.0005) and in MCI and AD were associated with MMSE changes. Both measures were additionally associated with ADAS-cog and trails-B in MCI patients, and ventricular expansion was associated with ADAS-cog in AD patients. Brain atrophy (p < 0.0005) and ventricular expansion rates (p = 0.001) were higher in MCI subjects who progressed to AD within 12 months of follow-up compared with MCI subjects who remained stable. MCI subjects who progressed to AD within 12 months had similar atrophy rates to AD subjects.Conclusion: Whole-brain atrophy rates and ventricular enlargement differed between patient groups and healthy controls, and tracked disease progression and psychological decline, demonstrating their relevance as biomarkers. [ABSTRACT FROM AUTHOR]

A tradeoff between immune response and life history traits, in particular growth rate, has been documented in various bird species. Ostriches are fast-growing birds and a typical feature of cohorts is that offspring often differ greatly in size. We investigated the relationship between hatching date and growth rate of chicks and both cell-mediated (measured using a phytohaemagglutinin (PHA) injection) and humoral immune responses in ostrich chicks maintained on a research farm. Chicks with higher growth rates had intermediate responses to both diphtheria and tetanus toxoids. By contrast, no relation between growth rates and responses to PHA injection were found. We conclude that chick growth rate variation may be explained beyond a certain threshold by a tradeoff between the humoral response and growth. Both responses to PHA injection and humoral responses in chicks were found to decrease with chick hatching date. Within the context of ostrich farming, these results could partially explain size variations observed in cohorts of chicks, as well as high mortality rates during their first 3 months of age. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. The development of much needed specific antiviral therapies and an effective vaccine has been hampered by the lack of a convenient small animal model. The determinants restricting HCV tropism to human and chimpanzee hosts are unknown. Replication of the viral RNA has been demonstrated in mouse cells, but these cells are not infectable with either lentiviral particles bearing HCV glycoproteins (HCVpp) or HCV produced in cell culture (HCVcc) (A.P., M.E. and C.M.R., unpublished observations), suggesting that there is a block at the level of entry. Here we show, using an iterative complementary DNA library screening approach, that human occludin (OCLN) is an essential HCV cell entry factor that is able to render murine cells infectable with HCVpp. Similarly, OCLN is required for the HCV-susceptibility of human cells, because its overexpression in uninfectable cells specifically enhanced HCVpp uptake, whereas its silencing in permissive cells impaired both HCVpp and HCVcc infection. In addition to OCLN, HCVpp infection of murine cells required expression of the previously identified HCV entry factors CD81 (ref. 4), scavenger receptor class B type I (SR-BI, also known as SCARB1) and claudin-1 (CLDN1). Although the mouse versions of SR-BI and CLDN1 function at least as well as the human proteins in promoting HCV entry, both OCLN and CD81 must be of human origin to allow efficient infection. The species-specific determinants of OCLN were mapped to its second extracellular loop. The identification of OCLN as a new HCV entry factor further highlights the importance of the tight junction complex in the viral entry process, and provides an important advance towards efforts to develop small animal models for HCV. [ABSTRACT FROM AUTHOR]

Molecular electronic devices show promise for future applications, but assessment of their utility is limited by the lack of physically based engineering models. In this paper, quantum-mechanical results obtained with density-functional theory (DFT) are used as a starting point to construct an efficient device-level model of a prototype molecular electronic device consisting of a metal/benzene-1,4-dithiolate/metal junction. This model is based on a physically transparent analytical expression with a few parameters that are fitted to DFT results and experimental data. We demonstrate that the model describes the I–V characteristics of the device accurately and is computationally efficient for implementation within a circuit simulator. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is a leading cause of cirrhosis and liver cancer worldwide. A better understanding of the viral life cycle, including the mechanisms of entry into host cells, is needed to identify novel therapeutic targets. Although HCV entry requires the CD81 co-receptor, and other host molecules have been implicated, at least one factor critical to this process remains unknown (reviewed in refs 1–3). Using an iterative expression cloning approach we identified claudin-1 (CLDN1), a tight junction component that is highly expressed in the liver, as essential for HCV entry. CLDN1 is required for HCV infection of human hepatoma cell lines and is the first factor to confer susceptibility to HCV when ectopically expressed in non-hepatic cells. Discrete residues within the first extracellular loop (EL1) of CLDN1, but not protein interaction motifs in intracellular domains, are critical for HCV entry. Moreover, antibodies directed against an epitope inserted in the CLDN1 EL1 block HCV infection. The kinetics of this inhibition indicate that CLDN1 acts late in the entry process, after virus binding and interaction with the HCV co-receptor CD81. With CLDN1 we have identified a novel key factor for HCV entry and a new target for antiviral drug development. [ABSTRACT FROM AUTHOR]

Many popcorn strains cannot be fertilized by pollen of dent and flint strains although the reciprocal crosses are successful. Similarly, plants of some annual teosinte populations can fertilize maize but do not accept its pollen. Single genes or gene complexes govern these two unilateral barriers to crossing. Failure of fertilization could reflect active rejection by the pistil of pollen containing a contrasting allele (incompatibility). Alternatively, the pistil could require presence of a matching allele in pollen (congruity). To distinguish between these possibilities genetically, the receptivity to pollen having both alleles was determined. If there is active rejection, heteroallelic pollen would not be accepted; if presence of a matching allele is required, heteroallelic pollen would be accepted. In both the popcorn and teosinte crossing barrier systems, heteroallelic pollen functioned, consistent with the congruity model. [ABSTRACT FROM AUTHOR]

Continuous development, the absence of a germline, flexible and reversible cellular differentiation, and the existence of haploid and diploid generations - both of which express genes - are characteristics that distinguish plants from animals. Because these differences alter the impact of mutations, animals and plants experience varied selection pressures. Despite different life-cycles, both flowering plants and multicellular animals have evolved complex sensing mechanisms that act after fertilization as 'quality checks' on reproduction, and that detect chromosome dosage and the parent of origin for specific genes. Although flowering plant embryos escape such surveillance in vitro, embryo success in the seed often depends on a healthy endosperm - a nutritive tissue that is produced by a second fertilization event in which maternal and paternal gene contributions can be monitored immediately after fertilization and throughout development. [ABSTRACT FROM AUTHOR]

Eukaryotic cells contain two distinct genomes. One is located in the nucleus (nDNA) and is transmitted in a mendelian fashion, whereas the other is located in mitochondria (mtDNA) and is transmitted by maternal inheritance. Cloning of mammals typically has been achieved via nuclear transfer, in which a donor somatic cell is fused by electoporation with a recipient enucleated oocyte. During this whole-cell electrofusion, nDNA as well as mtDNA ought to be transferred to the oocyte. Thus, the cloned progeny should harbour mtDNAs from both the donor and recipient cytoplasms, resulting in heteroplasmy. Although the confirmation of nuclear transfer has been established using somatic cell-specific nDNA markers, no similar analysis of the mtDNA genotype has been reported. We report here the origin of the mtDNA in Dolly, the first animal cloned from an established adult somatic cell line, and in nine other nuclear transfer-derived sheep generated from fetal cells. The mtDNA of each of the ten nuclear-transfer sheep was derived exclusively from recipient enucleated oocytes, with no detectable contribution from the respective somatic donor cells. Thus, although these ten sheep are authentic nuclear clones, they are in fact genetic chimaeras, containing somatic cell-derived nuclear DNA but oocyte-derived mtDNA. [ABSTRACT FROM AUTHOR]

For intersexual selection to occur, it is necessary that females choose between males. It is now well appreciated that constraints exist, which preclude females sampling all the available males in a population. These constraints are likely to have caused the evolution of sampling rules (such as the “best-of- n” rule) by which females sample males. Here we investigate the impact of female subsampling of the male population, not on the evolution of sampling behaviour, but on the population-level correlation between a male trait and currencies such as reproductive success. This study is important as it illustrates when population-level correlations can be safely used to infer the presence and strength of sexual selection in the field. We find that the correlation between a male trait and a mate choice variable rises steeply as the number of males sampled by each female increases, flattening above seven to ten males sampled. This shape is found to be remarkably robust, and little affected by, for example, the mate choice variable used, by noise in assessment, by sampling behaviour depending on female quality, or by population size. The only variable found to have a large impact is male clumping according to their “quality”. If females are sampling about four males, the maximum correlation that can be found at the population level is in the range 0.4–0.6, perhaps as little as 0.1 if males are strongly clumped. A recent review of the literature suggests that four is the average number of males that females sample. Thus, the absence of a strong correlation cannot by itself be used to infer that sexual selection is weak, as it may be due to females sampling few males. [ABSTRACT FROM AUTHOR]

Among the various host cellular processes that are hijacked by flaviviruses, few mechanisms have been described with regard to viral egress. Here we investigate how flaviviruses exploit Src family kinases (SFKs) for exit from infected cells. We identify Lyn as a critical component for secretion of Dengue and Zika infectious particles and their corresponding virus like particles (VLPs). Pharmacological inhibition or genetic depletion of the SFKs, Lyn in particular, block virus secretion. Lyn−/− cells are impaired in virus release and are rescued when reconstituted with wild-type Lyn, but not a kinase- or palmitoylation-deficient Lyn mutant. We establish that virus particles are secreted in two distinct populations – one as free virions and the other enclosed within membranes. Lyn is critical for the latter, which consists of proteolytically processed, infectious virus progenies within autophagosome-derived vesicles. This process depends on Ulk1, Rab GTPases and SNARE complexes implicated in secretory but not degradative autophagy and occur with significantly faster kinetics than the conventional secretory pathway. Our study reveals a previously undiscovered Lyn-dependent exit route of flaviviruses in LC3+ secretory organelles that enables them to evade circulating antibodies and might affect tissue tropism. Egress of flaviviruses and involved host pathways are not well understood. Here, the authors show that Lyn is a critical host kinase for Dengue and Zika virus egress resulting in infectious virus progenies within autophagosome-derived vesicles, which might help the virus to evade antibody responses. [ABSTRACT FROM AUTHOR]

Zika virus is a mosquito-borne flavivirus closely related to dengue virus that can cause severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Specific treatments and vaccines for Zika virus are not currently available. Here, we isolate and characterize four monoclonal antibodies (mAbs) from an infected patient that target the non-structural protein NS1. We show that while these antibodies are non-neutralizing, NS1-specific mAbs can engage FcγR without inducing antibody dependent enhancement (ADE) of infection in vitro. Moreover, we demonstrate that mAb AA12 has protective efficacy against lethal challenges of African and Asian lineage strains of Zika virus in Stat2-/- mice. Protection is Fc-dependent, as a mutated antibody unable to activate known Fc effector functions or complement is not protective in vivo. This study highlights the importance of the ZIKV NS1 protein as a potential vaccine antigen. [ABSTRACT FROM AUTHOR]

Purpose of Review: Assessing the cardiovascular risk associated with hypertriglyceridemia can be challenging due to frequent confounding conditions such as hypertension, diabetes mellitus, and hyperlipidemia. We sought to quantify this risk by examining several meta-analyses as well as subgroup analyses of previously published major randomized controlled trials that focused on the treatment of hyperlipidemia.Recent Findings: Recent trials measuring the effects of PCSK9 inhibitors such as evolocumab and alirocumab on cardiovascular outcomes have demonstrated a high degree of residual cardiovascular risk even after profound reductions in low-density-lipoprotein cholesterol (LDL-C).Summary: Despite optimization of LDL-C through the use of statins, PCSK9 inhibitors and adjunctive therapies such as ezetimibe, bile acid sequestrants and niacin, residual cardiovascular risk remains significant. Several ongoing trials are assessing the efficacy of pemafibrate and omega-3 fatty acids for the treatment of hypertriglyceridemia and their effects on major cardiovascular outcomes. [ABSTRACT FROM AUTHOR]