A comprehensive evaluation of alignment algorithms in the context of RNA-seq.

Transcriptome sequencing (RNA-Seq) overcomes limitations of previously used RNA quantification methods and provides one experimental framework for both high-throughput characterization and quantification of transcripts at the nucleotide level. The first step and a major challenge in the analysis of such experiments is the mapping of sequencing reads to a transcriptomic origin including the identification of splicing events. In recent years, a large number of such mapping algorithms have been developed, all of which have in common that they require algorithms for aligning a vast number of reads to genomic or transcriptomic sequences. Although the FM-index based aligner Bowtie has become a de facto standard within mapping pipelines, a much larger number of possible alignment algorithms have been developed also including other variants of FM-index based aligners. Accordingly, developers and users of RNA-seq mapping pipelines have the choice among a large number of available alignment algorithms. To provide guidance in the choice of alignment algorithms for these purposes, we evaluated the performance of 14 widely used alignment programs from three different algorithmic classes: algorithms using either hashing of the reference transcriptome, hashing of reads, or a compressed FM-index representation of the genome. Here, special emphasis was placed on both precision and recall and the performance for different read lengths and numbers of mismatches and indels in a read. Our results clearly showed the significant reduction in memory footprint and runtime provided by FM-index based aligners at a precision and recall comparable to the best hash table based aligners. Furthermore, the recently developed Bowtie 2 alignment algorithm shows a remarkable tolerance to both sequencing errors and indels, thus, essentially making hash-based aligners obsolete

Transdifferentiation from cornea to lens in Xenopus laevis depends on BMP signalling and involves upregulation of Wnt signalling

<p>Abstract</p> <p>Background</p> <p>Surgical removal of the lens from larval <it>Xenopus laevis </it>results in a rapid transdifferention of central corneal cells to form a new lens. The trigger for this process is understood to be an induction event arising from the unprecedented exposure of the cornea to the vitreous humour that occurs following lens removal. The molecular identity of this trigger is unknown.</p> <p>Results</p> <p>Here, we have used a functional transgenic approach to show that BMP signalling is required for lens regeneration and a microarray approach to identify genes that are upregulated specifically during this process. Analysis of the array data strongly implicates Wnt signalling and the Pitx family of transcription factors in the process of cornea to lens transdifferentiation. Our analysis also captured several genes associated with congenital cataract in humans. Pluripotency genes, in contrast, were not upregulated, supporting the idea that corneal cells transdifferentiate without returning to a stem cell state. Several genes from the array were expressed in the forming lens during embryogenesis. One of these, <it>Nipsnap1</it>, is a known direct target of BMP signalling.</p> <p>Conclusions</p> <p>Our results strongly implicate the developmental Wnt and BMP signalling pathways in the process of cornea to lens transdifferentiation (CLT) in <it>Xenopus</it>, and suggest direct transdifferentiation between these two anterior eye tissues.</p

Segment-specific optogenetic stimulation in Drosophila melanogaster with linear arrays of organic light-emitting diodes

This research was financially supported by the EPSRC NSF-CBET lead agency agreement (EP/R010595/1, 1706207), the DARPA-NESD programme (N66001-17-C-4012) and the Leverhulme Trust (RPG-2017-231). C.M. acknowledges funding from the European Commission through a Marie Skłodowska Curie individual fellowship (703387). S.R.P acknowledges funding from the Biology and Biotechnology Research council (BB/M021793). M.C.G. acknowledges funding from the Alexander von Humboldt Stiftung (Humboldt-Professorship).Optogenetics allows light-driven, non-contact control of neural systems, but light delivery remains challenging, in particular when fine spatial control of light is required to achieve local specificity. Here, we employ organic light-emitting diodes (OLEDs) that are micropatterned into linear arrays to obtain precise optogenetic control in Drosophila melanogaster larvae expressing the light-gated activator CsChrimson and the inhibitor GtACR2 within their peripheral sensory system. Our method allows confinement of light stimuli to within individual abdominal segments, which facilitates the study of larval behaviour in response to local sensory input. We show controlled triggering of specific crawling modes and find that targeted neurostimulation in abdominal segments switches the direction of crawling. More broadly, our work demonstrates how OLEDs can provide tailored patterns of light for photo-stimulation of neuronal networks, with future implications ranging from mapping neuronal connectivity in cultures to targeted photo-stimulation with pixelated OLED implants in vivo.Publisher PDFPeer reviewe

Gas network development in a precompacted bentonite experiment: evidence of generation and evolution

In a deep geological disposal facility for radioactive waste, precompacted bentonite is proposed as a sealing material for the isolation of boreholes, disposal galleries and deposition holes. The advective movement of repository gas in bentonite has been linked to the development of new porosity and propagation of dilatant pathways. For the first time we present a detailed analysis of stress field data during the generation and evolution of a gas network. A new experimental dataset, from a highly instrumented test, clearly shows the strong coupling between stress, gas pressure and flow in bentonite. Multiple discrete propagation events are observed, demonstrating spatial variability and time-dependency as permeability within the clay develops. Analysis of the stress data before, during and after gas entry indicates a heterogeneous stress field initially develops, resulting from the development of these pathways. The flow network is dynamic and continues to spatially evolve after gas entry, such that permeability under these conditions must be time-dependent in nature. Perturbation of the stress field is significant before all major gas outflow events, presumably resulting from the requirement to propagate an effective gas network before outflow is possible. In contrast, no major flow perturbations are detected which did not correlate with fluctuations in the stress field. The controls on the distribution and geometry of the resulting flow network are unclear, as well as its long-term evolution and stability. These will be beneficial in the assessment of gas pressure evolution as part of safety case development

The iconography of Asphyxiophilia: From fantasmatic fetish to forensic fact

This is a post print version of the article. The official published version can be accessed from the link below

The suppression of appetite and food consumption by methylphenidate: the moderating effects of gender and weight status in healthy adults.

Females typically show greater behavioural responses to stimulant drugs than males, including loss of appetite; as seen, for example, in those who use methylphenidate (MP) therapeutically for treatment of attention deficit hyperactivity disorder (ADHD). This is a relevant issue because of the strong link between ADHD and obesity. In a sample (n=132) of normal-weight (BMI25) and obese (BMI30) men and women we assessed appetite, cravings, and snack-food intake in response to MP (0.5 mg/kg) and placebo. Results indicated a significant three-way interaction for the three dependent variables--food-related responding diminishing in all groups from placebo to MP, except in obese males who showed no decreases to the MP challenge. These data show for the first time the existence of gender differences in the appetite response to MP, and are relevant for finding a dopamine pathway to new weight-loss medications, which would be utilized differently in males than in females

Outflow obstruction after living donor liver transplantation managed with a temporary vena cava filter:A case report

Introduction: Outflow obstruction is a rare but critical vascular complication in liver transplantation, which may lead to graft loss and mortality. We report a case of caval vein outflow obstruction due to retrohepatic compression after living donor liver transplantation (LDLT), which was managed by temporary implantation of a vena cava filter. Presentation of case: A 63-year-old male with end stage liver disease presented with caval vein outflow obstruction and massive ascites 12 days after right lobe LDLT. We opted for a minimally invasive approach and implanted a vena cava filter at the compressed site through transjugular route. The patient's ascites drainage significantly decreased and graft function maintained stable after the intervention. On day 50 posttransplant, the filter was successfully removed and the patient was discharged without complications. Discussion: Outflow obstruction after liver transplantation can result from anastomotic stenosis, graft size mismatch, thrombosis or compression of the outflow tract. Various management strategies have been employed both peri- and posttransplant, ranging from surgical interventions to minimally-invasive techniques. The treatment strategy should be tailored to the individual case, considering the timing of presentation and the specific cause for the obstruction. Conclusion: We successfully managed a case of compressive outflow obstruction by temporary implantation of a vena cava filter after LDLT. The vena cava filter was safely removed under angiography.</p

Off-World Mental Health:Considerations for the Design of Well-being-Supportive Technologies for Deep Space Exploration

During future long-duration space exploration missions, humans will be exposed to combinations of extreme physical, psychological, and interpersonal demands. These demands create risks for the safety, performance, health, and well-being of both individuals and crew. The communication latency in deep space means that explorers will increasingly have to operate independently and take responsibility for their own self-care and self-management. At present, several research programs are focused on developing and testing digital technologies and countermeasures that support the effective functioning of deep space crews. Although promising, these initiatives have been stimulated mostly by technological opportunity rather than cogent theory. In this perspective, we argue that digital technologies developed for spaceflight should be informed by well-being–supportive design principles and be cognizant of broader conversations around the development and use of digital health applications, especially pertaining to issues of autonomy, privacy, and trust. These issues are important for designing potentially mission-critical health technologies and may be determining factors in the safe and successful completion of future off-world endeavors.publishedVersio

Adverse events among high-risk participants in a home-based walking study: a descriptive study

Abstract Background For high-risk individuals and their healthcare providers, finding the right balance between promoting physical activity and minimizing the risk of adverse events can be difficult. More information on the prevalence and influence of adverse events is needed to improve providers' ability to prescribe effective and safe exercise programs for their patients. Methods This study describes the type and severity of adverse events reported by participants with cardiovascular disease or at-risk for cardiovascular disease that occurred during an unsupervised, home-based walking study. This multi-site, randomized controlled trial tested the feasibility of a diet and lifestyle activity intervention over 1.5 years. At month 13, 274 eligible participants (male veterans) were recruited who were ambulatory, BMI > 28, and reporting one or more cardiovascular disease risk factors. All participants attended five, face-to-face dietitian-delivered counseling sessions during the six-month intervention. Participants were randomized to three study arms: 1) time-based walking goals, 2) simple pedometer-based walking goals, and 3) enhanced pedometer-based walking goals with Internet-mediated feedback. Two physicians verified adverse event symptom coding. Results Enrolled participants had an average of five medical comorbidities. During 1110 person months of observation, 87 of 274 participants reported 121 adverse events. One serious study-related adverse event (atrial fibrillation) was reported; the individual resumed study participation within three days. Non-serious, study related adverse events made up 12% of all symptoms – predominantly minor musculoskeletal events. Serious, non-study related adverse events represented 32% of all symptoms while non-serious, non-study related adverse events made up 56% of symptoms. Cardiovascular disease events represented over half of the non-study related adverse event symptoms followed by musculoskeletal complaints. Adverse events caused 50 temporary suspensions averaging 26 days in duration before physician medical clearance was obtained to resume walking. Conclusion Men at high risk for adverse cardiovascular events can safely be advised to start a progressive walking program. Results suggest that minor to serious medical problems unrelated to exercise are a major barrier to walking adherence. Helping individuals with chronic illness return to physical activity quickly but safely after an adverse event is an important component of any physical activity intervention targeting this population.http://deepblue.lib.umich.edu/bitstream/2027.42/112714/1/12966_2007_Article_97.pd