Joy is a Strategy: How We Sparkle Together

The authors reflect on their leadership experiences in the NERL consortium, suggesting that purposefully pursuing joy in collaborative work offers an alternative to traditional academic structures that dismiss affect in favor of stoic isolation and competition

Cap-Independent Translation in Hematological Malignancies.

Hematological malignancies are a heterogeneous group of diseases deriving from blood cells progenitors. Although many genes involved in blood cancers contain internal ribosome entry sites (IRESes), there has been only few studies focusing on the role of cap-independent translation in leukemia and lymphomas. Expression of IRES trans-acting factors can also be altered, and interestingly, BCL-ABL1 fusion protein expressed from "Philadelphia" chromosome, found in some types of leukemia, regulates several of them. A mechanism involving c-Myc IRES and cap-independent translation and leading to resistance to chemotherapy in multiple myeloma emphasize the contribution of cap-independent translation in blood cancers and the need for more work to be done to clarify the roles of known IRESes in pathology and response to chemotherapeutics

The impact of riluzole on neurobehavioral outcomes in preclinical models of traumatic and nontraumatic spinal cord injury: results from a systematic review of the literature

Study Design:Systematic review.Objective:To evaluate the impact of riluzole on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic spinal cord injury (SCI).Methods:An extensive search of the literature was conducted in Medline, EMBASE, and Medline in Process. Studies were included if they evaluated the impact of riluzole on neurobehavioral outcomes in preclinical models of nontraumatic and traumatic SCI. Extensive data were extracted from relevant studies, including sample characteristics, injury model, outcomes assessed, timing of evaluation, and main results. The SYRCLE checklist was used to assess various sources of bias.Results:The search yielded a total of 3180 unique citations. A total of 16 studies were deemed relevant and were summarized in this review. Sample sizes ranged from 14 to 90, and injury models included traumatic SCI (n = 9), degenerative cervical myelopathy (n = 2), and spinal cord-ischemia (n = 5). The most commonly assessed outcome measures were BBB (Basso, Beattie, Besnahan) locomotor score and von Frey filament testing. In general, rats treated with riluzole exhibited significantly higher BBB locomotor scores than controls. Furthermore, riluzole significantly increased withdrawal thresholds to innocuous stimuli and tail flick latency following application of radiant heat stimuli. Finally, rats treated with riluzole achieved superior results on many components of gait assessment.Conclusion:In preclinical models of traumatic and nontraumatic SCI, riluzole significantly improves locomotor scores, gait function, and neuropathic pain. This review provides the background information necessary to interpret the results of clinical trials on the impact of riluzole in traumatic and nontraumatic SCI

Cap-Independent Translation in Hematological Malignancies.

Hematological malignancies are a heterogeneous group of diseases deriving from blood cells progenitors. Although many genes involved in blood cancers contain internal ribosome entry sites (IRESes), there has been only few studies focusing on the role of cap-independent translation in leukemia and lymphomas. Expression of IRES trans-acting factors can also be altered, and interestingly, BCL-ABL1 fusion protein expressed from "Philadelphia" chromosome, found in some types of leukemia, regulates several of them. A mechanism involving c-Myc IRES and cap-independent translation and leading to resistance to chemotherapy in multiple myeloma emphasize the contribution of cap-independent translation in blood cancers and the need for more work to be done to clarify the roles of known IRESes in pathology and response to chemotherapeutics

Dark energy constraints from cosmic shear power spectra: impact of intrinsic alignments on photometric redshift requirements

Cosmic shear constrains cosmology by exploiting the apparent alignments of pairs of galaxies due to gravitational lensing by intervening mass clumps. However galaxies may become (intrinsically) aligned with each other, and with nearby mass clumps, during their formation. This effect needs to be disentangled from the cosmic shear signal to place constraints on cosmology. We use the linear intrinsic alignment model as a base and compare it to an alternative model and data. If intrinsic alignments are ignored then the dark energy equation of state is biased by ~50 per cent. We examine how the number of tomographic redshift bins affects uncertainties on cosmological parameters and find that when intrinsic alignments are included two or more times as many bins are required to obtain 80 per cent of the available information. We investigate how the degradation in the dark energy figure of merit depends on the photometric redshift scatter. Previous studies have shown that lensing does not place stringent requirements on the photometric redshift uncertainty, so long as the uncertainty is well known. However, if intrinsic alignments are included the requirements become a factor of three tighter. These results are quite insensitive to the fraction of catastrophic outliers, assuming that this fraction is well known. We show the effect of uncertainties in photometric redshift bias and scatter. Finally we quantify how priors on the intrinsic alignment model would improve dark energy constraints.Comment: 14 pages and 9 figures. Replaced with final version accepted in "Gravitational Lensing" Focus Issue of the New Journal of Physics at http://www.iop.org/EJ/abstract/1367-2630/9/12/E0

Neurocognitive correlates of probable posttraumatic stress disorder following traumatic brain injury

Introduction: Neurocognitive problems associated with posttraumatic stress disorder (PTSD) can interact with impairment resulting from traumatic brain injury (TBI). Research question: We aimed to identify neurocognitive problems associated with probable PTSD following TBI in a civilian sample. Material and methods: The study is part of the CENTER-TBI project (Collaborative European Neurotrauma Effectiveness Research) that aims to better characterize TBI. For this cross-sectional study, we included patients of all severities aged over 15, and a Glasgow Outcome Score Extended (GOSE) above 3. Participants were assessed at six months post-injury on the PTSD Checklist-5 (PCL-5), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT) and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Primary analysis was a complete case analysis. Regression analyses were performed to investigate the association between the PCL-5 and cognition. Results: Of the 1134 participants included in the complete case analysis, 13.5% screened positive for PTSD. Probable PTSD was significantly associated with higher TMT-(B-A) (OR ​= ​1.35, 95% CI: 1.14–1.60, p ​&lt; ​.001) and lower RAVLT-delayed recall scores (OR ​= ​0.74, 95% CI: 0.61–0.91, p ​= ​.004) after controlling for age, sex, psychiatric history, baseline Glasgow Coma Scale and education. Discussion and conclusion: Poorer performance on cognitive tests assessing task switching and, to a lesser extent, delayed verbal recall is associated with probable PTSD in civilians who have suffered TBI.</p

Discovery and genotyping of structural variation from long-read haploid genome sequence data

In an effort to more fully understand the full spectrum of human genetic variation, we generated deep single-molecule, real-time (SMRT) sequencing data from two haploid human genomes. By using an assembly-based approach (SMRT-SV), we systematically assessed each genome independently for structural variants (SVs) and indels resolving the sequence structure of 461,553 genetic variants from 2 bp to 28 kbp in length. We find that &gt;89% of these variants have been missed as part of analysis of the 1000 Genomes Project even after adjusting for more common variants (MAF &gt; 1%). We estimate that this theoretical human diploid differs by as much as ∼16 Mbp with respect to the human reference, with long-read sequencing data providing a fivefold increase in sensitivity for genetic variants ranging in size from 7 bp to 1 kbp compared with short-read sequence data. Although a large fraction of genetic variants were not detected by short-read approaches, once the alternate allele is sequence-resolved, we show that 61% of SVs can be genotyped in short-read sequence data sets with high accuracy. Uncoupling discovery from genotyping thus allows for the majority of this missed common variation to be genotyped in the human population. Interestingly, when we repeat SV detection on a pseudodiploid genome constructed in silico by merging the two haploids, we find that ∼59% of the heterozygous SVs are no longer detected by SMRT-SV. These results indicate that haploid resolution of long-read sequencing data will significantly increase sensitivity of SV detection.</jats:p