bluuebunny/crossref_metadata_2025_split huggingface dataset:
Awareness of fifth metatarsal stress fractures among soccer coaches in Japan: A cross-sectional study
Authors: Miyamori Takayuki , Yoshimura Masafumi 
Published: November 2022

AbstractAlthough a fifth metatarsal stress fracture is the most frequent stress fracture in soccer players, knowledge of fifth metatarsal stress fractures among soccer coaches is unclear. Therefore, we performed an online survey of soccer coaches affiliated with the Japan Football Association to assess their knowledge of fifth metatarsal stress fractures. A total of 117 soccer coaches participated in an original online survey. Data on age, sex, types of coaching license, coaching category, types of training surface, awareness of fifth metatarsal stress fractures, and measures employed to prevent fifth metatarsal stress fractures were collected using the survey. A total of 87/117 coaches were aware of fifth metatarsal stress fractures; however, only 30% reported awareness of preventive and treatment measures for fifth metatarsal stress fractures. Licensed coaches (i.e., licensed higher than level C) were also more likely to be aware of fifth metatarsal stress fractures than were unlicensed coaches. Furthermore, although playing on artificial turf is an established risk factor for numerous sports injuries, soccer coaches who usually trained on artificial turf were more likely to be unaware of the risks associated with fifth metatarsal stress fractures than were coaches who trained on other surfaces (e.g., clay fields). Soccer coaches in the study population were generally aware of fifth metatarsal stress fractures; however, most of them were not aware of specific treatment or preventive training strategies for fifth metatarsal stress fractures. Additionally, coaches who practiced on artificial turf were not well educated on fifth metatarsal stress fractures. Our findings raise awareness of fifth metatarsal stress fractures to improve the education of soccer coaches regarding injury prevention strategies.
Differential Memory Impairment Across Relational Domains in Temporal Lobe Epilepsy
Authors: Tavakol Shahin , Kebets Valeria , Royer Jessica , Li Qiongling , Auer Hans , DeKraker Jordan , Jefferies Elizabeth , Bernasconi Neda , Bernasconi Andrea , Helmstaedter Christoph , Caciagli Lorenzo , Frauscher Birgit , Smallwood Jonathan , Bernhardt Boris 
Published: November 2022

ABSTRACTBackgroundTemporal lobe epilepsy (TLE) is typically associated with pathology of the hippocampus, a key structure involved in relational memory processes, including episodic, semantic, and spatial memory. While it is widely accepted that TLE-associated hippocampal alterations may underlie global deficits in memory, it remains poorly understood whether TLE may present with shared or unique impairment across distinct relational memory domains.MethodsWe administered a recently validated behavioral paradigm to evaluate episodic, semantic, and spatial memory in 20 pharmacoresistant TLE patients and 53 age- and sex-matched healthy controls. We implemented linear mixed effects models to identify memory deficits in individuals with TLE relative to controls, and used partial least squares analysis to identify factors contributing to overall variations in relational memory performance across both cohorts.ResultsTLE patients showed marked impairment in episodic memory compared to controls, while spatial and semantic memory remained relatively intact. Findings were robust, with slight decreases in effect sizes after controlling for performance on executive function tests. Via partial least squares analysis, we identified group, age, and bilateral hippocampal volumes as important variables relating to relational memory impairment.ConclusionOur behavioral framework provides a granular approach for assessing relational memory deficits in people with TLE and may inform future prognostic strategies in patients with hippocampal pathology. Our work warrants further investigations into the underlying neural substrates of relational memory.
Phosphatidylethanolamine facilitates mitochondrial pyruvate entry to regulate metabolic flexibility
Authors: Siripoksup Piyarat , Cao Guoshen , Cluntun Ahmad A. , Maschek J. Alan , Pearce Quentinn , Lang Marisa J. , Eshima Hiroaki , Opurum Precious C. , Mahmassani Ziad S. , Taylor Eric B. , Cox James E. , Drummond Micah J. , Rutter Jared , Funai Katsuhiko 
Published: November 2022

AbstractCarbohydrates and lipids provide the majority of substrates to fuel mitochondrial oxidative phosphorylation (OXPHOS). Metabolic inflexibility, defined as an impaired ability to switch between these fuels, is implicated in a number of metabolic diseases. Here we explore the mechanism by which physical inactivity promotes metabolic inflexibility in skeletal muscle. We developed a mouse model of sedentariness by small mouse cage (SMC) that, unlike other classic models of disuse in mice, faithfully recapitulates metabolic responses that occur in humans. Bioenergetic phenotyping of mitochondria displayed metabolic inflexibility induced by physical inactivity, demonstrated by a reduction in pyruvate-stimulated respiration (JO2) in absence of a change in palmitate-stimulatedJO2. Pyruvate resistance in these mitochondria was likely driven by a decrease in phosphatidylethanolamine (PE) abundance in the mitochondrial membrane. Reduction in mitochondrial PE by deletion of phosphatidylserine decarboxylase (PSD) was sufficient to induce metabolic inflexibility measured at the whole-body level, as well as at the level of skeletal muscle mitochondria. Low mitochondrial PE was sufficient to increase glucose flux towards lactate. We further implicate that resistance to pyruvate metabolism is due to attenuated mitochondrial entry via mitochondrial pyruvate carrier (MPC). These findings suggest a novel mechanism by which mitochondrial PE directly regulates MPC activity to modulate metabolic flexibility.
Pyrophosphate-Mediated Repair of Damaged and Mismatched RNA by a Polymerase Ribozyme
Authors: Kent Alexandra D. , Yang Lucy L. , Lee Ivee A. , Lupták Andrej 
Published: November 2022

AbstractPrior to the emergence of the contemporary biosphere, the early Earth is likely to have progressed through an RNA-based world. In such an evolving world, it would have been critical to have a system of genome replication that allowed heritable information to be transferred with an early catalyst, such as an RNA polymerase ribozyme. Though substantial effort has gone into evolving such a polymerase, many variants suffer from premature termination and low fidelity, resulting in low yields of full-length sequences and small quantities of active sequences, respectively. The ability to replicate and maintain a genome at a higher fidelity would lend an evolutionary advantage to an early evolvable system. Cells today achieve this through a variety of means, including complex damage repair mechanisms and proofreading pathways, but such dedicated machinery would likely not exist in an early evolving world. However, if an early polymerase possessed repair activity under specific conditions, replication would have been improved. Here we demonstrate the first example of ribozyme-mediated repair of damaged and mismatched RNA sequences. Under conditions of high pyrophosphate concentrations, we show that a polymerase ribozyme can repair RNA sequences terminated in a 2′ −3′ cyclic phosphate, a mismatch, or both, to allow further polymerization along a template. In many cases, the fidelity of the repaired RNA extension is significantly higher than priming from a mismatched base-pair; this observation suggests that mutations may have an allosteric effect on the fidelity of downstream replication. Finally, we show that the pyrophosphorolysis reaction directly yields a nucleoside triphosphate, providing the first evidence for ribozyme-catalyzed production of ATP. Increased fidelity and processivity of polymerization advances the longstanding goal of developing a self-replicating polymerase ribozyme.
CooccurrenceAffinity: An R package for computing a novel metric of affinity in co-occurrence data that corrects for pervasive errors in traditional indices
Authors: Mainali Kumar P. , Slud Eric 
Published: November 2022

ABSTRACTAnalysis of co-occurrence data in ecology and biogeography with traditional indices has led to many problems. In our recent study (Mainali, Slud, Singer, & Fagan, 2022), we revealed the source of the problem that makes the traditional indices fundamentally flawed and completely unreliable, and we further developed a novel metric of association, alpha, with complete formulation of the null distribution for estimating the mechanism of affinity. We also developed the maximum likelihood estimate (MLE) of alpha in our prior study.Here, we introduce theCooccurrenceAffinityR package that computes alpha MLE. We provide functions to perform the analysis based on a 2×2 contingency table of occurrence/co-occurrence counts as well as a m×n presence-absence matrix (e.g., species by site matrix). The flexibility of the function allows a user to compute the alpha MLE for entity pairs on matrix columns based on presence-absence states recorded in the matrix rows, or for entities on matrix rows based on presence-absence recorded in columns. We also provide functions for plotting the computed indices.As novel components of this software paper not reported in the original study, we present theoretical discussions about median interval and four types of confidence intervals; we further develop functions (a) to compute those intervals, (b) to evaluate their true coverage probability of enclosing the population parameter, and (c) to generate figures.CooccurrenceAffinityis a practical and efficient R package with user-friendly functions for end-to-end analysis and plotting of co-occurrence data in various formats, making it possible to compute the recently developed metric of alpha MLE as well as its median and confidence intervals introduced in this paper. The package supplements its main output of the novel metric of association with the three most common traditional indices of association in co-occurrence data: Jaccard, Sørensen–Dice, and Simpson.
Proteomic analysis of spermathecal fluid reveals factors related to long-term sperm storage in ant queens
Authors: Gotoh Ayako 
Published: November 2022

AbstractAnt queens can maintain a large number of sperm cells for over a decade after mating at the beginning of their adult lives until they die. This ability is prominent because sperm cells cannot maintain their fertilization ability long after ejaculation in animals; however, the cellular mechanisms remain unclear. Sperm cells are maintained in the female sperm storage organ, the spermatheca, which supplies a suitable environment for sperm cells. To reveal the molecular basis of the long-term sperm storage mechanisms in ant queens, protein profiles enriched in the spermathecal fluid relative to the hemolymph were identified inLasius japonicususing mass spectrometry-based proteomics. Proteins related to the extracellular matrix, antioxidant, metabolic pathways, proteases, and with uncharacterized functions were enriched in the spermathecal fluid relative to the hemolymph. These enriched proteins were shared with highly expressed genes previously detected by transcriptome analyses of the spermatheca in queens ofCrematogaster osakensisbelonging to a different subfamily thanL. japonicus. It is considered that the ability for long-term sperm storage has evolved in the early ant lineage; therefore, the common proteins identified in the two ant species are crucial for this ability.
The fine-scale recombination rate variation and associations with genomic features in a butterfly
Authors: i Torres Aleix Palahí , Höök Lars , Näsvall Karin , Shipilina Daria , Wiklund Christer , Vila Roger , Pruisscher Peter , Backström Niclas 
Published: November 2022

AbstractGenetic recombination is a key molecular mechanism that has profound implications on both micro- and macro-evolutionary processes. However, the determinants of recombination rate variation in holocentric organisms are poorly understood, in particular in Lepidoptera (moths and butterflies). The wood white butterfly (Leptidea sinapis) shows considerable intraspecific variation in chromosome numbers and is a suitable system for studying regional recombination rate variation and its potential molecular underpinnings. Here, we developed a large wholegenome resequencing data set from a population of wood whites to obtain high-resolution recombination maps using linkage disequilibrium information. The analyses revealed that larger chromosomes had a bimodal recombination landscape, potentially due to interference between simultaneous chiasmata. The recombination rate was significantly lower in subtelomeric regions, with exceptions associated with segregating chromosome rearrangements, showing that fissions and fusions can have considerable effects on the recombination landscape. There was no association between the inferred recombination rate and base composition, supporting a negligible influence of GC-biased gene conversion in butterflies. We found significant but variable associations between the recombination rate and the density of different classes of transposable elements (TEs), most notably a significant enrichment of SINEs in genomic regions with higher recombination rate. Finally, the analyses unveiled significant enrichment of genes involved in farnesyltranstransferase activity in recombination cold-spots, potentially indicating that expression of transferases can inhibit formation of chiasmata during meiotic division. Our results provide novel information about recombination rate variation in holocentric organisms and has particular implications for forthcoming research in population genetics, molecular/genome evolution and speciation.
Consensus design and engineering of an efficient and high-yield Peptide Asparaginyl Ligase
Authors: Hemu Xinya , Zhang Xiaohong , Chang Hong Yi , En Poh Jin , Tam James P. 
Published: November 2022

AbstractPlant legumains are Asn/Asp-specific endopeptidases (AEPs) that have diverse functions in plants. Peptide asparaginyl ligases (PALs) are a special legumain subtype that primarily catalyze peptide bond formation rather than hydrolysis. PALs are versatile protein engineering tools but are rarely found in nature. To overcome this limitation, here we describe a two-step method to design and engineer a high-yield and efficient recombinant PAL based on commonly found AEPs. We first constructed a consensus sequence derived from 1,500 plant legumains to design the evolutionarily stable legumain conLEG that could be produced inE. coliwith 20-fold higher yield relative to that for natural legumains. We then applied the LAD (ligase-activity determinant) hypothesis to exploit conserved residues in PAL substrate-binding pockets and convert conLEG into conPAL1-3. Functional studies showed that conLEG is primarily a hydrolase, whereas conPALs are ligases. Importantly, conPAL3 is a super-efficient and broadly active PAL for peptide and protein cyclization.
Minor variations in multicellular life cycles have major effects on adaptation
Authors: Isaksson Hanna , Brännström Åke , Libby Eric 
Published: November 2022

AbstractMulticellularity has evolved several independent times over the past hundreds of millions of years and given rise to a wide diversity of complex life. Recent studies have found that large differences in the fundamental structure of early multicellular life cycles can affect fitness and influence multicellular adaptation. Yet, there is an underlying assumption that at some scale or categorization multicellular life cycles are similar in terms of their adaptive potential. Here, we consider this possibility by exploring adaptation in a class of simple multicellular life cycles of filamentous organisms that only differ in one respect, how many daughter filaments are produced. We use mathematical models and evolutionary simulations to show that despite the similarities, qualitatively different mutations fix. In particular, we find that mutations with a tradeoff between cell growth and group survival, i.e. “selfish” or “altruistic” traits, spread differently. Specifically, altruistic mutations more readily spread in life cycles that produce few daughters while in life cycles producing many daughters either type of mutation can spread depending on the environment. Our results show that subtle changes in multicellular life cycles can fundamentally alter adaptation.Author summaryEarly forms of multicellular organisms exhibit a wide range of life cycles. Though studies have explored how the structure of a life cycle determines the fitness of early multicellular organisms, far less is known about how it affects their adaptation. Studies that do investigate adaptation typically focus on large scale differences between life cycles, implicitly assuming that at some scale life cycles are similar in terms of their adaptation. In this study we consider this assumption by analyzing adaptation in a class of early multicellular life cycles where the only difference between them is the number of offspring they produce. We use mathematical models and evolutionary simulations to compute the fate of mutations that are either altruistic or selfish, depending on their effects on single cells and the groups to which they belong. We find that despite the similarity between life cycles they can adapt very differently. In particular, life cycles that produce few offspring consistently adapt via altruistic traits, while life cycles that produce many offspring adapt via either altruistic or selfish traits depending on the environment. Ultimately, we find that small scale differences in multicellular life cycles can have large effects on adaptation.
Cellpanelr: identify predictive biomarkers from cell line panel response data
Authors: Wassarman Douglas R. , Wu Taiasean , Shokat Kevan M. 
Published: November 2022

AbstractSummaryCellpanelr is an open-source R package and web application for analyzing user-generated cell panel screens using DepMap data sets. Cellpanelr can be used to identify mutation and expression biomarkers of cell line response, increasing the value and accessibility of cell panel experiments such as relative sensitivities to cancer drugs.Availability and implementationHosted web application is available from shinyapps.io (https://dwassarman.shinyapps.io/cellpanelr). Source code and installation instructions are available from GitHub (https://github.com/dwassarman/cellpanelr).Contactdwassar@gmail.com
Towards universal synthetic heterotrophy using a metabolic coordinator
Authors: Sullivan Sean F. , Shetty Anuj , Bharadwaj Tharun , Krishna Naveen , Trivedi Vikas D. , Gopinarayanan Venkatesh Endalur , Chappell Todd C. , Sellers Daniel M. , Kumar R. Pravin , Nair Nikhil U. 
Published: November 2022

ABSTRACTEngineering the utilization of non-native substrates, or synthetic heterotrophy, in proven industrial microbes such asSaccharomyces cerevisiaerepresents an opportunity to valorize plentiful and renewable sources of carbon and energy as potential inputs to biotechnological processes. We previously demonstrated that activation of the galactose (GAL) regulon, a regulatory structure used by this yeast to coordinate substrate utilization with biomass formation during growth on galactose, during growth on the non-native substrate xylose results in a vastly altered gene expression profile and faster growth compared with constitutive overexpression of the same heterologous catabolic pathway. However, this effort involved the creation of a xylose-inducible variant of Gal3p (Gal3pS25144.1), the sensor protein of the GAL regulon, preventing this semi-synthetic regulon approach from being easily adapted to additional non-native substrates. Here, we report the construction of a variant Gal3pMC (metabolic coordinator) that exhibits robust GAL regulon activation in the presence of structurally diverse substrates and recapitulates the dynamics of the native system. Multiple molecular modeling studies confirm that Gal3pMCoccupies conformational states corresponding to galactose-bound Gal3p in an inducer-independent manner. Using Gal3pMCto test a regulon approach to the assimilation of the non-native lignocellulosic sugars xylose, arabinose, and cellobiose yields higher growth rates and final cell densities when compared with a constitutive overexpression of the same set of catabolic genes. The subsequent demonstration of rapid and complete co-utilization of all three non-native substrates suggests that Gal3pMC-mediated dynamic global gene expression changes by GAL regulon activation may be universally beneficial for engineering synthetic heterotrophy.
TheBRCA1isoform, BRCA1-IRIS, operates independently of the full-length BRCA1 in the Fanconi anemia pathway
Authors: Li Andrew G. , Chan Brenda C. , Murphy Elizabeth C. , He Ye , Ors Muhammed , Kong Qing , Cantor Sharon B. , Brugge Joan S. , Brown Myles , Livingston David M. 
Published: November 2022

SummaryThe tumor suppressorBRCA1encodes multiple protein products including the canonical BRCA1-p220 (p220), which plays important roles in repair of diverse types of DNA damage. However, contributions of otherBRCA1-encoded protein isoforms to DNA damage repair are less clear. Here, we report that the BRCA1-IRIS (IRIS) isoform has critical functions in the Fanconi anemia (FA) pathway and in repair of DNA interstrand crosslinks (ICLs). Loss of IRIS expression sensitizes cells to ICLs and impairs ICL repair. ICL formation stimulates association of IRIS with both FANCD2 and the FA core complex, which promotes FANCD2 recruitment to damage sites. The unique,BRCA1intron 11-encoded C-terminal tail of IRIS is required for complex formation with FANCD2 and for ICL-inducible FANCD2 mono-ubiquitylation. Collectively, our findings reveal that IRIS plays an essential role, upstream of the p220-directed HR, in the FA pathway through a previously unrecognized mechanism that depends on the IRIS-FANCA-FANCD2 interaction.HighlightsBRCA1splicing isoform BRCA1-IRIS is required for interstrand crosslink (ICL) repair.BRCA1-IRIS interacts with FANCD2 and promotes its recruitment to sites of ICL damage.BRCA1-IRIS, but not BRCA1-p220, promotes ICL-inducible FANCD2 mono-ubiquitylation.The unique C-terminal tail of BRCA1-IRIS is essential for its function in ICL repair.
Combining Transcranial Magnetic Stimulation with Antidepressants: A Systematic Review and Meta-Analysis
Authors: Rakesh Gopalkumar , Cordero Patrick , Khanal Rebika , Himelhoch Seth S. , Rush Craig R. 
Published: November 2022

AbstractMajor depressive disorder (MDD) imposes significant disability on patients. In addition to antidepressants, brain stimulation modalities such as electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) have been helpful in treatment of MDD. Novel TMS paradigms like theta burst stimulation (TBS) have rapidly become popular due to their effectiveness.Given that both antidepressants and TMS are commonly used together and affect neuroplasticity, we reviewed studies that administered both these as treatments for MDD. Unlike ECT wherein previous trials have shown that continuing pharmacotherapy is useful while giving ECT, there are no consensus guidelines on what to do with antidepressants when starting TMS. So, we reviewed two groups of studies – 1) those that administered TMS and antidepressant pharmacotherapy concurrently and 2) those wherein TMS augmented antidepressants or were an adjunctive intervention to antidepressants. We performed a meta-analysis for randomized clinical trials (RCTs) that administered TMS and antidepressants concurrently.We found ten RCTs fulfilling criteria 1 and compared uniformly titrated antidepressant regimens combined with active versus sham TMS. We also found twenty studies fulfilling criterion 2, that used TMS as an augmenting or adjunctive intervention. Both groups of studies showed TMS combined with antidepressants had greater efficacy for treatment of MDD. We advocate for laboratory studies examining the interaction between TMS and antidepressants in a parametric fashion; in addition to randomized controlled trials that examine this combination to expedite remission in MDD.