Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Beliefs about others' intentions determine whether cooperation is the faster choice

Is collaboration the fast choice for humans? Past studies proposed that cooperation is a behavioural default, based on Response Times (RT) findings. Here we contend that the individual’s reckoning of the immediate social environment shapes her predisposition to cooperate and, hence, response latencies. In a social dilemma game, we manipulate the beliefs about the partner’s intentions to cooperate and show that they act as a switch that determines cooperation and defection RTs; when the partner’s intention to cooperate is perceived as high, cooperation choices are speeded up, while defection is slowed down. Importantly, this social context effect holds across varying expected payoffs, indicating that it modulates behaviour regardless of choices’ similarity in monetary terms. Moreover, this pattern is moderated by individual variability in social preferences: Among conditional cooperators, high cooperation beliefs speed up cooperation responses and slow down defection. Among free-riders, defection is always faster and more likely than cooperation, while high cooperation beliefs slow down all decisions. These results shed new light on the conflict of choices account of response latencies, as well as on the intuitive cooperation hypothesis, and can help to correctly interpret and reconcile previous, apparently contradictory results, by considering the role of context in social dilemmas

The Effects of Two Types of Sleep Deprivation on Visual Working Memory Capacity and Filtering Efficiency

Sleep deprivation has adverse consequences for a variety of cognitive functions. The exact effects of sleep deprivation, though, are dependent upon the cognitive process examined. Within working memory, for example, some component processes are more vulnerable to sleep deprivation than others. Additionally, the differential impacts on cognition of different types of sleep deprivation have not been well studied. The aim of this study was to examine the effects of one night of total sleep deprivation and 4 nights of partial sleep deprivation (4 hours in bed/night) on two components of visual working memory: capacity and filtering efficiency. Forty-four healthy young adults were randomly assigned to one of the two sleep deprivation conditions. All participants were studied: 1) in a well-rested condition (following 6 nights of 9 hours in bed/night); and 2) following sleep deprivation, in a counter-balanced order. Visual working memory testing consisted of two related tasks. The first measured visual working memory capacity and the second measured the ability to ignore distractor stimuli in a visual scene (filtering efficiency). Results showed neither type of sleep deprivation reduced visual working memory capacity. Partial sleep deprivation also generally did not change filtering efficiency. Total sleep deprivation, on the other hand, did impair performance in the filtering task. These results suggest components of visual working memory are differentially vulnerable to the effects of sleep deprivation, and different types of sleep deprivation impact visual working memory to different degrees. Such findings have implications for operational settings where individuals may need to perform with inadequate sleep and whose jobs involve receiving an array of visual information and discriminating the relevant from the irrelevant prior to making decisions or taking actions (e.g., baggage screeners, air traffic controllers, military personnel, health care providers)

Scoliosis treatment using a combination of manipulative and rehabilitative therapy: a retrospective case series

BACKGROUND: The combination of spinal manipulation and various physiotherapeutic procedures used to correct the curvatures associated with scoliosis have been largely unsuccessful. Typically, the goals of these procedures are often to relax, strengthen, or stretch musculotendinous and/or ligamentous structures. In this study, we investigate the possible benefits of combining spinal manipulation, positional traction, and neuromuscular reeducation in the treatment of idiopathic scoliosis. METHODS: A total of 22 patient files were selected to participate in the protocol. Of these, 19 met the study criterion required for analysis of treatment benefits. Anteroposterior radiographs were taken of each subject prior to treatment intervention and 4–6 weeks following the intervention. A Cobb angle was drawn and analyzed on each radiograph, so pre and post comparisons could be made. RESULTS: After 4–6 weeks of treatment, the treatment group averaged a 17° reduction in their Cobb angle measurements. None of the patients' Cobb angles increased. A total of 3 subjects were dismissed from the study for noncompliance relating to home care instructions, leaving 19 subjects to be evaluated post-intervention. CONCLUSIONS: The combined use of spinal manipulation and postural therapy appeared to significantly reduce the severity of the Cobb angle in all 19 subjects. These results warrant further testing of this protocol

The completion of the Mammalian Gene Collection (MGC)

Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis. The MGC now contains clones with the entire protein-coding sequence for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession) transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq transcripts that have one or more PubMed publications, in addition to clones for more than 6300 rat genes. These high-quality MGC clones and their sequences are accessible without restriction to researchers worldwide

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin