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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]

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]

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]

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]

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]

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]

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]

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]

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]