Rag GTPases are cardioprotective by regulating lysosomal function.

The Rag family proteins are Ras-like small GTPases that have a critical role in amino-acid-stimulated mTORC1 activation by recruiting mTORC1 to lysosome. Despite progress in the mechanistic understanding of Rag GTPases in mTORC1 activation, little is known about the physiological function of Rag GTPases in vivo. Here we show that loss of RagA and RagB (RagA/B) in cardiomyocytes results in hypertrophic cardiomyopathy and phenocopies lysosomal storage diseases, although mTORC1 activity is not substantially impaired in vivo. We demonstrate that despite upregulation of lysosomal protein expression by constitutive activation of the transcription factor EB (TFEB) in RagA/B knockout mouse embryonic fibroblasts, lysosomal acidification is compromised owing to decreased v-ATPase level in the lysosome fraction. Our study uncovers RagA/B GTPases as key regulators of lysosomal function and cardiac protection

The Malay Peninsula as a barrier to gene flow in an Asian horseshoe crab species, Carcinoscorpius rotundicauda Latreille

Horseshoe crabs are marine arthropods that are amongst the oldest living creatures that still exist today. Among the four extant species of horseshoe crabs, Carcinoscorpius rotundicauda differs from the other species by having poisonous eggs and lays its eggs in sandy-mud areas near river mouths. With the rapid development of coastal areas worldwide, C. rotundicauda habitats are decreasing. Until now, however, there has not been any study on the species' genetic variation. Simple sequence repeat (SSR) and inter-simple sequence repeat (ISSR) markers were employed to study the genetic variation in five C. rotundicauda populations from the east and west coasts of the Malay Peninsula. Both markers showed differing levels of genetic variation, but concurred on the pattern of genetic structuring among populations of the species. This includes showing that little, although significant, genetic differentiation is present among populations, suggesting a low rate of gene flow among populations. The results also suggested that C. rotundicauda may be subjected to the land barrier effect of the Malay Peninsula, whereby gene flow is limited between populations occurring on both sides of the peninsula, increasing their genetic differentiation through time

Dissolved heavy metals and water quality in the surface waters of rivers and drainages of the West Peninsular Malaysia

The dissolved concentrations of metals (Cd, Cu, Pb, Ni, Fe and Zn), temperature, total dissolved solids, pH, dissolved oxygen, salinity and conductivity were determined in the surface waters of 24 geographical sampling sites including city and urban drainages and rivers, from the west Peninsular Malaysia, collected in January to April 2005. From these sampling sites, the ranges (min-max) of dissolved metal concentrations (mg/L) were Cd: 0.001-0.055, Cu: 0.001-0.1773, Pb: 0.001-1.523, Ni: 0.001-0.246, Fe: 0.001-35.67 and Zn: 0.0001-0.609 while for the water quality are pH: 4.96-9.81, dissolved oxygen (0.39-7.26 mg/L), total dissolved solids (0.002-10.02 mg/L), salinity (0.00-8.93 ppt), conductivity (3.33-17423 μS/cm) and temperature (27.8-35.3�). Some sites with elevated dissolved concentrations of heavy metals and poor water quality indicated the anthropogenic inputs of industrial and urban wastes. Regular monitoring of water quality in all drainage waters is recommended

Genetic variation within and relationships among populations of Asian goats (Capra hircus)

Genetic variation at 59 protein coding loci (16 polymorphic) and 25 microsatellite loci was analysed for 11 indigenous south-east Asian goat populations, and the Australian feral population, to determine the magnitude of genetic differentiation and the genetic relationships among the populations. Significant deviations from Hardy–Weinberg equilibrium were detected in one or more populations for eight of the nine protein loci with codominant alleles, and for microsatellites for all except the two Sri Lankan populations and for all but four loci. For both marker types, average inbreeding coefficients (FIS) were exceptionally high. Heterogeneity of deviations from Hardy–Weinberg equilibrium for the microsatellites showed no differences for among loci within populations as compared with among populations within loci. For protein loci, however, the former was higher, indicating selection affecting allele frequencies at some loci. The variance among protein loci was significantly higher than among microsatellite loci, further indicating selection at some protein loci. There was significant differentiation among populations for both protein and microsatellite loci, most likely reflecting the geography of south-east Asia, and the presumed spread of goats throughout the region. Phylogenies derived from pair-wise genetic distance estimates show some similar clustering for the microsatellite and protein based trees, but bootstrap support was generally low for both. A phylogeny based on the combined set of 38 protein and microsatellite loci showed better consistency with geography and higher bootstrap values. The genetic distance phylogeny and the Weitzman diversity tree derived from microsatellite data showed some identical clusters, and both identified the Ujung Pandang and Australia populations as contributing most to overall genetic diversity

Osteointegration of soft tissue grafts within the bone tunnels in anterior cruciate ligament reconstruction can be enhanced

Anterior cruciate ligament reconstruction with a soft tissue autograft (hamstring autograft) has grown in popularity in the last 10 years. However, the issues of a relatively long healing time and an inferior histological healing result in terms of Sharpey-like fibers connection in soft tissue grafts are still unsolved. To obtain a promising outcome in the long run, prompt osteointegration of the tendon graft within the bone tunnel is essential. In recent decades, numerous methods have been reported to enhance osteointegration of soft tissue graft in the bone tunnel. In this article, we review the current literature in this research area, mainly focusing on strategies applied to the local bone tunnel environment. Biological strategies such as stem cell and gene transfer technology, as well as the local application of specific growth factors have been reported to yield exciting results. The use of biological bone substitute and physical stimulation also obtained promising results. Artificially engineered tissue has promise as a solution to the problem of donor site morbidity. Despite these encouraging results, the current available evidence is still experimental. Further clinical studies in terms of randomized control trial in the future should be conducted to extrapolate these basic science study findings into clinical practice. © 2009 Springer-Verlag.postprin

Resistance of Brazilian diamondback moth populations to insecticides

Plutella xylostella is a recurring pest on cruciferous crops around the world. In Brazil, it typically requires large number of insecticide sprays, which may lead to fast evolution of resistance. The aim of this study was to assess the susceptibility of Brazilian diamondback moth populations to the insecticides abamectin, deltamethrin, and spinosad. Leaf dip bioassays were used to determine mortality data obtained after 48 h of exposure to insecticides and subjected to Probit analysis. The population from Bonito, state of Pernambuco, Brazil, had the highest toxicity ratio (20.2 - fold) to abamectin compared to the reference population. The LC50 values for deltamethrin ranged from 85.2 to 360.1 mg L-1, demonstrating a high survival of populations in relation to this insecticide field dose rate (7.5 mg L-1). The toxicity ratios of the estimated LC50s, however, were very low (varying from 2.2 - to 4.2 - fold). Most populations exhibited toxicity ratios for spinosad, ranging from 2.3 - to 5.1 - fold, while both the LC50 and LC95 values reflected a high susceptibility to the spinosad field dosage (120 mg L-1). Only the Bonito - PE population resisted to abamectin, while all P. xylostella populations were resistant to deltamethrin, but particularly susceptible to spinosad because of the absence of selection pressure with it in these areas.Plutella xylostella é uma praga recorrente em brássicas de todo o mundo. No Brasil, normalmente exige grande número de pulverizações de inseticidas, que pode levar à rápida evolução da resistência. Avaliou-se a suscetibilidade de populações brasileiras da traça das crucíferas aos inseticidas abamectina, deltametrina e espinosade. Bioensaios de imersão de folhas foram utilizados para determinar a mortalidade, sendo os dados obtidos após 48 h de exposição aos inseticidas e submetidos à análise de Probit. A população de Bonito-PE apresentou a maior razão de toxicidade (20,2 vezes) para abamectina em relação à população de referência. Os valores de CL50s para deltametrina variaram entre 85,2 - 360,1 mg L-1, demonstrando alta sobrevivência das populações a este inseticida com relação à dose de campo (7,5 mg L-1). Entretanto, as razões de toxicidade das CL50 estimadas foram muito baixas (variando de 2,2 a 4,2 vezes). A maioria das populações apresentou razões de toxicidade para espinosade, variando de 2,3 para 5,1 vezes, embora os valores de CL demonstram alta suscetibilidade delas à dose de campo para espinosade (120 mg L-1). Apenas a população de Bonito PE apresentou resistência a abamectina, enquanto todas as populações de P. xylostella estão resistentes a deltametrina, mas suscetíveis ao espinosade particularmente devido à ausência de pressão de seleção com este nestas áreas

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe