Time since injury influences eccentric hamstring force imbalance in collegiate American football players

Hamstring injuries (HSI) are among the most common non-contact injuries in American football. Understanding effects of duration since injury may inform how coaches, trainers, and athletes approach rehabilitation and return to play decisions. PURPOSE: To compare hamstring imbalance in athletes injured more than 12 months ago to hamstring imbalance in athletes with no HSI and compare hamstring imbalance in athletes injured within the last 12 months to imbalance in those with no HSI. METHODS: Sixty-one collegiate football players (age: 22.5 ± 1.8, height: 187.6 ± 6.2 cm, weight: 105 ± 21.6 kg) rostered in 2022 self-identified as having either (1) no HSI (n=45), or (2) having injured only one hamstring since grade 9. We separated those reporting previous injuries into two groups: those with injury longer ago than 12 months (historical HSI, n=12) and those injured with the last 12 months (recent HSI, n=4). All players performed eccentric hamstring curls on a Nordbord. For the group with no HSI, imbalance between legs was calculated as the stronger minus weaker leg. For both injured groups, imbalance was calculated as the difference between uninjured and injured legs. RESULTS: Analysis of the means was performed via Bayesian methods, assuming separate standard deviations for each group. Analysis of posterior chains indicated all parameters converged appropriately. The posterior mean of imbalance for players with no HSI was 34.7 ± 27.4 N. The posterior mean of imbalance in those with historical HSI was 10.8 ± 51.1 N. The posterior mean of imbalance in players with recent HSI was 48.9 ± 46.4 N. The posterior probability that the difference between imbalance of the no HSI group and the imbalance of the historical HSI group is greater than zero was 0.948, and the posterior probability that the imbalance of those with recent HSI and the imbalance of the no HSI group is greater than zero is 0.767. CONCLUSION: Collegiate football players with no HSI have greater hamstring imbalance than do those with historical HSI, implying healing process, rehabilitation efforts, and habitual movement patterns may reduce imbalance between hamstrings over a period of at least 12 months. As expected, players who have recent HSI demonstrate greater hamstring imbalance than players with no HSI

CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.

Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases

Tissue-specific alternative polyadenylation at the imprinted gene Mest regulates allelic usage at Copg2

The gene Mest (also known as Peg1) is regulated by genomic imprinting in the mouse and only the paternal allele is active for transcription. MEST is similarly imprinted in humans, where it is a candidate for the growth retardation Silver-Russell syndrome. The MEST protein belongs to an ancient family of hydrolases but its function is still unknown. It is highly conserved in vertebrates although imprinted expression is only observed in marsupials and eutherians, thus a recent evolutionary event. Here we describe the identification of new imprinted RNA products at the Mest locus, longer variants of the RNA, called MestXL, transcribed >10 kb into the downstream antisense gene Copg2. During development MestXL is produced exclusively in the developing central nervous system (CNS) by alternative polyadenylation. Copg2 is biallelically expressed in the embryo except in MestXL-expressing tissues, where we observed preferential expression from the maternal allele. To analyze the function of the MestXL transcripts in Copg2 regulation, we studied the effects of a targeted allele at Mest introducing a truncation in the mRNA. We show that both the formation of the MestXL isoforms and the allelic bias at Copg2 are lost in the CNS of mutants embryos. Our results propose a new mechanism to regulate allelic usage in the mammalian genome, via tissue-specific alternative polyadenylation and transcriptional interference in sense–antisense pairs at imprinted loci

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

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

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

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The Rise and Fall, and the Rise (Again) of Feminist Research in Music: 'What Goes Around Comes Around'

This article reports from a two-phase study that involved an analysis of the extant literature followed by a three-part survey answered by seventy-one women composers. Through these theoretical and empirical data, the authors explore the relationship between gender and music’s symbolic and cultural capital. Bourdieu’s theory of the habitus is employed to understand the gendered experiences of the female composers who participated in the survey. The article suggests that these female composers have different investments in gender but that, overall, they reinforce the male habitus given that the female habitus occupies a subordinate position in relation to that of the male. The findings of the study also suggest a connection between contemporary feminism and the attitudes towards gender held by the participants. The article concludes that female composers classify themselves, and others, according to gendered norms and that these perpetuate the social order in music in which the male norm dominates

The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium inaugural meeting report

The Metagenomics and Metadesign of the Subways and Urban Biomes (MetaSUB) International Consortium is a novel, interdisciplinary initiative comprised of experts across many fields, including genomics, data analysis, engineering, public health, and architecture. The ultimate goal of the MetaSUB Consortium is to improve city utilization and planning through the detection, measurement, and design of metagenomics within urban environments. Although continual measures occur for temperature, air pressure, weather, and human activity, including longitudinal, cross-kingdom ecosystem dynamics can alter and improve the design of cities. The MetaSUB Consortium is aiding these efforts by developing and testing metagenomic methods and standards, including optimized methods for sample collection, DNA/RNA isolation, taxa characterization, and data visualization. The data produced by the consortium can aid city planners, public health officials, and architectural designers. In addition, the study will continue to lead to the discovery of new species, global maps of antimicrobial resistance (AMR) markers, and novel biosynthetic gene clusters (BGCs). Finally, we note that engineered metagenomic ecosystems can help enable more responsive, safer, and quantified cities