Automatic Neuron Detection in Calcium Imaging Data Using Convolutional Networks

Calcium imaging is an important technique for monitoring the activity of thousands of neurons simultaneously. As calcium imaging datasets grow in size, automated detection of individual neurons is becoming important. Here we apply a supervised learning approach to this problem and show that convolutional networks can achieve near-human accuracy and superhuman speed. Accuracy is superior to the popular PCA/ICA method based on precision and recall relative to ground truth annotation by a human expert. These results suggest that convolutional networks are an efficient and flexible tool for the analysis of large-scale calcium imaging data.Comment: 9 pages, 5 figures, 2 ancillary files; minor changes for camera-ready version. appears in Advances in Neural Information Processing Systems 29 (NIPS 2016

The Health and Structural Consequences of Acute Knee Injuries Involving Rupture of the Anterior Cruciate Ligament

Although there is an abundance of literature regarding the development of knee osteoarthritis after rupture of the anterior cruciate ligament (ACL), the mechanism underlying this link is not clear. Recent studies have reported that several factors may be predictive of the development of osteoarthritis, including damage to the menisci and articular cartilage during the initial trauma, altered knee biomechanics after injury, and episodic instability. This article summarizes recent developments in the understanding of the joint damage resulting from an ACL tear, and the influence that current and future treatment methods may have on the long-term progression to osteoarthritis

Shiga toxin 2 overexpression in Escherichia coli O157:H7 strains associated with severe human disease

Variation in disease severity among Escherichia coli O157:H7 infections may result from differential expression of Shiga toxin 2 (Stx2). Eleven strains belonging to four prominent phylogenetic clades, including clade 8 strains representative of the 2006 U.S. spinach outbreak, were examined for stx2 expression by real-time PCR and western blot analysis. Clade 8 strains were shown to overexpress stx2 basally, and following induction with ciprofloxacin when compared to strains from clades 1-3. Differences in stx2 expression generally correlated with Stx2 protein levels. Single-nucleotide polymorphisms identified in regions upstream of stx2AB in clade 8 strains were largely absent in non-clade 8 strains. This study concludes that stx2 overexpression is common to strains from clade 8 associated with hemolytic uremic syndrome, and describes SNPs which may affect stx2 expression and which could be useful in the genetic differentiation of highly-virulent strains.Microbiology and Molecular Genetic

The induction and identification of novel Colistin resistance mutations in Acinetobacter baumannii and their implications.

Acinetobacter baumannii is a significant cause of opportunistic hospital acquired infection and has been identified as an important emerging infection due to its high levels of antimicrobial resistance. Multidrug resistant A. baumannii has risen rapidly in Vietnam, where colistin is becoming the drug of last resort for many infections. In this study we generated spontaneous colistin resistant progeny (up to >256 μg/μl) from four colistin susceptible Vietnamese isolates and one susceptible reference strain (MIC <1.5 μg/μl). Whole genome sequencing was used to identify single nucleotide mutations that could be attributed to the reduced colistin susceptibility. We identified six lpxACD and three pmrB mutations, the majority of which were novel. In addition, we identified further mutations in six A. baumannii genes (vacJ, pldA, ttg2C, pheS and conserved hypothetical protein) that we hypothesise have a role in reduced colistin susceptibility. This study has identified additional mutations that may be associated with colistin resistance through novel resistance mechanisms. Our work further demonstrates how rapidly A. baumannii can generate resistance to a last resort antimicrobial and highlights the need for improved surveillance to identified A. baumannii with an extensive drug resistance profile

Increased Adherence and Expression of Virulence Genes in a Lineage of Escherichia coli O157:H7 Commonly Associated with Human Infections

Enterohemorrhagic Escherichia coli (EHEC) O157:H7, a food and waterborne pathogen, can be classified into nine phylogenetically distinct lineages, as determined by single nucleotide polymorphism genotyping. One lineage (clade 8) was found to be associated with hemolytic uremic syndrome (HUS), which can lead to kidney failure and death in some cases, particularly young children. Another lineage (clade 2) differs considerably in gene content and is phylogenetically distinct from clade 8, but caused significantly fewer cases of HUS in a prior study. Little is known, however, about how these two lineages vary with regard to phenotypic traits important for disease pathogenesis and in the expression of shared virulence genes.Here, we quantified the level of adherence to and invasion of MAC-T bovine epithelial cells, and examined the transcriptomes of 24 EHEC O157:H7 strains with varying Shiga toxin profiles from two common lineages. Adherence to epithelial cells was >2-fold higher for EHEC O157:H7 strains belonging to clade 8 versus clade 2, while no difference in invasiveness was observed between the two lineages. Whole-genome 70-mer oligo microarrays, which probe for 6088 genes from O157:H7 Sakai, O157:H7 EDL 933, pO157, and K12 MG1655, detected significant differential expression between clades in 604 genes following co-incubation with epithelial cells for 30 min; 186 of the 604 genes had a >1.5 fold change difference. Relative to clade 2, clade 8 strains showed upregulation of major virulence genes, including 29 of the 41 locus of enterocyte effacement (LEE) pathogenicity island genes, which are critical for adherence, as well as Shiga toxin genes and pO157 plasmid-encoded virulence genes. Differences in expression of 16 genes that encode colonization factors, toxins, and regulators were confirmed by qRT-PCR, which revealed a greater magnitude of change than microarrays.These findings demonstrate that the EHEC O157:H7 lineage associated with HUS expresses higher levels of virulence genes and has an enhanced ability to attach to epithelial cells relative to another common lineage

Experimental evidence for the interacting effects of forest edge, moisture and soil macrofauna on leaf litter decomposition

a b s t r a c t Forest ecosystems have been widely fragmented by human land use. Fragmentation induces significant microclimatic and biological differences at the forest edge relative to the forest interior. Increased exposure to solar radiation and wind at forest edges reduces soil moisture, which in turn affects leaf litter decomposition. We investigate the effect of forest fragmentation, soil moisture, soil macrofauna and litter quality on leaf litter decomposition to test the hypothesis that decomposition will be slower at a forest edge relative to the interior and that this effect is driven by lower soil moisture at the forest edge. Experimental plots were established at Wytham Woods, UK, and an experimental watering treatment was applied in plots at the forest edge and interior. Decomposition rate was measured using litter bags of two different mesh sizes, to include or exclude invertebrate macrofauna, and containing leaf litter of two tree species: easily decomposing ash (Fraxinus excelsior L.) and recalcitrant oak (Quercus robur L.). The decomposition rate was moisture-limited at both sites. However, the soil was moister and decomposition for both species was faster in the forest interior than at the edge. The presence of macrofauna accelerated the decomposition rate regardless of moisture conditions, and was particularly important in the decomposition of the recalcitrant oak. However, there was no effect of the watering treatment on macrofauna species richness and abundance. This study demonstrates the effect of forest fragmentation on an important ecosystem process, providing new insights into the interacting effects of moisture conditions, litter quality, forest edge and soil macrofauna

Representations of sport in the revolutionary socialist press in Britain, 1988–2012

This paper considers how sport presents a dualism to those on the far left of the political spectrum. A long-standing, passionate debate has existed on the contradictory role played by sport, polarised between those who reject it as a bourgeois capitalist plague and those who argue for its reclamation and reformation. A case study is offered of a political party that has consistently used revolutionary Marxism as the basis for its activity and how this party, the largest in Britain, addresses sport in its publications. The study draws on empirical data to illustrate this debate by reporting findings from three socialist publications. When sport did feature it was often in relation to high profile sporting events with a critical tone adopted and typically focused on issues of commodification, exploitation and alienation of athletes and supporters. However, readers’ letters, printed in the same publications, revealed how this interpretation was not universally accepted, thus illustrating the contradictory nature of sport for those on the far left

The microRNA-29 family in cartilage homeostasis and osteoarthritis

MicroRNAs have been shown to function in cartilage development and homeostasis, as well as in progression of osteoarthritis. The objective of the current study was to identify microRNAs involved in the onset or early progression of osteoarthritis and characterise their function in chondrocytes. MicroRNA expression in mouse knee joints post-DMM surgery was measured over 7 days. Expression of miR-29b-3p was increased at day 1 and regulated in the opposite direction to its potential targets. In a mouse model of cartilage injury and in end-stage human OA cartilage, the miR-29 family were also regulated. SOX9 repressed expression of miR-29a-3p and miR-29b-3p via the 29a/b1 promoter. TGFβ1 decreased expression of miR-29a, b and c (3p) in primary chondrocytes, whilst IL-1β increased (but LPS decreased) their expression. The miR-29 family negatively regulated Smad, NFκB and canonical WNT signalling pathways. Expression profiles revealed regulation of new WNT-related genes. Amongst these, FZD3, FZD5, DVL3, FRAT2, CK2A2 were validated as direct targets of the miR-29 family. These data identify the miR-29 family as microRNAs acting across development and progression of OA. They are regulated by factors which are important in OA and impact on relevant signalling pathways