bluuebunny/crossref_metadata_2025_split huggingface dataset:
RedRibbon: A new rank-rank hypergeometric overlap pipeline to compare gene and transcript expression signatures
Authors: Piron Anthony , Szymczak Florian , Alvelos Maria Inês , Defrance Matthieu , Lenaerts Tom , Eizirik Décio L. , Cnop Miriam 
Published: September 2022

AbstractMotivationHigh throughput omics technologies have generated a wealth of large protein, gene and transcript datasets that have exacerbated the need for new methods to analyse and compare big datasets. Rank-rank hypergeometric overlap is an important threshold-free method to combine and visualize two ranked lists of P-values or fold-changes, usually from differential gene expression analyses. Here, we introduce a new rank-rank hypergeometric overlap-based method aimed at both gene level and alternative splicing analyses at transcript or exon level, hitherto unreachable as transcript numbers are an order of magnitude larger than gene numbers.ResultsWe tested the tool on synthetic and real datasets at gene and transcript levels to detect correlation and anti-correlation patterns and found it to be fast and accurate, even on very large datasets thanks to an evolutionary algorithm based minimal P-value search. The tool comes with a ready-to-use permutation scheme allowing the computation of adjusted P-values at low time cost. Additionally, the package is a drop-in replacement to previous packages as a compatibility mode is included, allowing to re-run older studies with close to no change to existing pipelines. RedRibbon holds the promise to accurately extricate detailed information from large analyses.AvailabilityRNA-sequencing datasets are available through the Gene Expression Omnibus (GEO) portal with accession numbers GSE159984, GSE133218, GSE137136, GSE98485, GSE148058 and GSE108413. The C libraries and R package code are open to the community with a permissive licence (GPL3) and available for download from GitHub https://github.com/antpiron/ale, https://github.com/antpiron/cRedRibbon and https://github.com/antpiron/RedRibbon.Contactanthony.piron@ulb.be
Solid-State Single-Molecule Sensing with the Electronic Life-detection Instrument for Enceladus/Europa (ELIE)
Authors: Carr Christopher E. , Ramírez-Colón José L. , Duzdevich Daniel , Lee Sam , Taniguchi Masateru , Ohshiro Takahito , Komoto Yuki , Soderblom Jason M. , Zuber M. T. 
Published: September 2022

AbstractGrowing evidence of the potential habitability of Ocean Worlds across our Solar System is motivating the advancement of technologies capable of detecting life as we know it – sharing a common ancestry or common physicochemical origin to life on Earth – or don’t know it, representing a distinct genesis event of life quite different than our one known example. Here, we propose the Electronic Life-detection Instrument for Enceladus/Europa (ELIE), a solid-state single-molecule instrument payload that aims to search for life based on the detection of amino acids and informational polymers (IPs) at the parts per billion to trillion level. As a first proof-of- principle in a laboratory environment, we demonstrate single-molecule detection of the amino acid L-proline at a 10 µM concentration in a compact system. Based on ELIE’s solid-state quantum electronic tunneling sensing mechanism, we further propose the quantum property of the HOMO–LUMO gap (energy difference between a molecule’s highest energy occupied molecular orbital and lowest energy unoccupied molecular orbital) as a novel approach to measure amino acid complexity. Finally, we assess the potential of ELIE to discriminate between abiotically and biotically derived (-amino acids in order to reduce false positive risk for life detection. Nanogap technology can also be applied to the detection of nucleobases and short sequences of IPs such as, but not limited to, RNA and DNA. Future missions may utilize ELIE to target preserved biosignatures on the surface of Mars, extant life in its deep subsurface, or life or its biosignatures in the plume, surface, or subsurface of ice moons such as Enceladus or Europa.One Sentence Summary:A solid-state nanogap can determine the abundance distribution of amino acids, detect nucleic acids, and shows potential for detecting life as we know it and life as we don’t.
Habitat use differences mediate anthropogenic threat exposure in white sturgeon
Authors: Walter Jonathan A. , Singer Gabriel P. , Reuman Daniel C. , Colborne Scott F. , Sheppard Lawrence W. , O’Donnell Daniel R. , Coombs Nat , Johnston Myfanwy , Miller Emily A. , Steel Anna E. , Kelly John T. , Fangue Nann A. , Rypel Andrew L. 
Published: September 2022

AbstractUnderstanding intraspecific variation in habitat use, particularly of long-lived fishes across multiple life history stages, is core to improved conservation management. Here, we present results from a synthesis of acoustic telemetry data for sub-adult and adult white sturgeon (Acipenser transmontanus) from 2010 to 2017 in the San Francisco Estuary and Sacramento River ecosystems. We focused primarily on uncovering spatial patterns of inferred habitat occupancy across life stages, and on linking habitat use to extant anthropogenic threats. We found substantial differences in habitat use across individuals and over time that was related to fish size classes defined relative to the slot limit (102-152 cm) used to regulate recreational fishing. However, differences in habitat use were not explained by fish sex or water year flow conditions. We also estimated indices of overall exposure for two major threats: capture by anglers and habitat modification. Fish of harvestable size were detected less often than others in areas where many are caught. Future monitoring and management of white sturgeon might benefit from examining multiple phases of white sturgeon life history. For example, additional tracking studies could improve our understanding of juvenile habitat use, adult survival rates, patterns of anadromy, and cross-basin habitat utilization.
Metabolic costs of walking and arm reaching in persons with mild multiple sclerosis
Authors: Courter Robert , Alvarez Enrique , Enoka Roger , Ahmed Alaa 
Published: September 2022

AbstractMovement slowness is a common and disruptive symptom of multiple sclerosis (MS). A potential cause is that individuals with MS slow down to conserve energy as a behavioral adjustment to heightened metabolic costs of movement. To investigate this prospect, we measured the metabolic costs of both walking and seated arm reaching at five speeds in persons with mild MS (pwMS; n = 13; 46.0 ± 7.7yrs) and sex- and age-matched controls (HCs; n = 13; 45.8 ± 7.8yrs). Notably, the cohort of pwMS was highly mobile and no individuals required a cane or aid when walking. We found that the net metabolic power of walking was approximately 20% higher for pwMS across all speeds (p = 0.0185). In contrast, we found no differences in the gross costs of reaching between pwMS and HCs (p = 0.492). Collectively, our results suggest that abnormal slowness of movement in MS – particularly reaching – is not the consequence of heightened effort costs alone. Our findings are consistent with the possibility that demyelination of reward regions of the central nervous system in MS disrupt the dopamine-mediated impetus to move more quickly and thereby prompt slower movements.NEW & NOTEWORTHYIndividuals with multiple sclerosis (MS) often move more slowly than those without the disease. A possible cause is that movements in MS are more energetically expensive and slowing is an adaptation to conserve metabolic resources. Here, we find that while walking is more costly for persons with MS, arm reaching movements are not. These results bring into question the driving force of movement slowness in MS and implicate other motor-related networks contributing to slowing.
Nicked tRNAs are stable reservoirs of tRNA halves in cells and biofluids
Authors: Costa Bruno , Calzi Marco Li , Castellano Mauricio , Blanco Valentina , Cuevasanta Ernesto , Litvan Irene , Ivanov Pavel , Witwer Kenneth , Cayota Alfonso , Tosar Juan Pablo 
Published: September 2022

ABSTRACTNonvesicular extracellular RNAs (nv-exRNAs) constitute the majority of the extracellular RNAome, but little is known about their stability, function and potential use as disease biomarkers. Herein, we measured the stability of several naked RNAs when incubated in human serum, urine and cerebrospinal fluid (CSF). We identified extracellularly produced tRNA-derived small RNAs (tDRs) with half-lives of up to three hours in CSF. Contrary to widespread assumptions, these intrinsically stable small RNAs are full-length tRNAs containing broken phosphodiester bonds (i.e., nicked tRNAs). Standard molecular biology protocols, including phenol-based RNA extraction and heat, induce the artifactual denaturation of nicked tRNAs and the consequent in vitro production of tDRs. Broken bonds are roadblocks for reverse transcriptases, preventing amplification and/or sequencing of nicked tRNAs in their native state. To solve this, we performed enzymatic repair of nicked tRNAs purified under native conditions, harnessing the intrinsic activity of phage and bacterial tRNA repair systems. Enzymatic repair regenerated an RNase R-resistant tRNA-sized band in northern blot and enabled RT-PCR amplification of full-length tRNAs. We also separated nicked tRNAs from tDRs by chromatographic methods under native conditions, identifying nicked tRNAs inside stressed cells and in vesicle-depleted human biofluids. Dissociation of nicked tRNAs produces single-stranded tDRs that can be spontaneously taken up by human epithelial cells, positioning stable nv-exRNAs as potentially relevant players in intercellular communication pathways.
Mitochondrial bioenergetic dysfunction and cryptic splicing of stathmin-2 are neuropathological markers of disease duration in sporadic amyotrophic lateral sclerosis
Authors: Mehta Arpan R. , McDade Karina , Newton Judith , Ruepp Marc-David , Pal Suvankar , Chandran Siddharthan , Smith Colin , Selvaraj Bhuvaneish T. 
Published: September 2022

AbstractA striking feature of sporadic amyotrophic lateral sclerosis (ALS) is the marked heterogeneity in disease duration; despite the stark median survival of three years from symptom onset, 10-20% of people with ALS survive longer than 10 years. An improved understanding of the mechanisms underpinning this is vital to revealing the biological basis of disease resilience. Accumulating experimental and pathological evidence implicates mitochondrial bioenergetic dysfunction and TDP-43 nuclear loss-of-function in the aetiopathogenesis of ALS. However, the relevance of these two molecular dysfunctions to disease duration and resilience in ALS is unknown. We curated a cohort of sporadic ALS cases comprising clinically linked autopsy samples to identify molecular neuropathological correlates of disease duration. We developed a novel dual BaseScope RNA in situ hybridisation probe that labels mitochondrial complex 1 transcript (MT-ND2) and truncated stathmin-2 (STMN2) transcripts to measure mitochondrial bioenergetic function and TDP-43 loss-of-function, respectively, in ventral horn neurons. We first show that there is dysfunctional mitochondrial bioenergetics in sporadic ALS. We observed reduced expression of MT-ND2 and increased expression of truncated STMN2 in ALS cases (N=20) compared to sex- and age-matched controls (N=10). We show that these findings correlate with ALS disease duration. Further mechanistic studies are needed to explore whether manipulation of STMN2 expression, by either suppressing cryptic splicing or overexpression, could modify disease duration.
Antibiotic Resistance associated with the COVID-19 Pandemic: A Rapid Systematic Review
Authors: Langford BJ , Soucy J-PR , Leung V , So M , Kwan ATH , Portnoff JS , Bertagnolio S , Raybardhan S , MacFadden D , Daneman N 
Published: September 2022

AbstractBackgroundCOVID-19 and antimicrobial resistance (AMR) are two intersecting global public health crises.ObjectiveWe aim to describe the impact of the COVID-19 pandemic on AMR across healthcare settings.Data SourceA search was conducted in December 2021 in World Health Organization’s COVID-19 Research Database with forward citation searching up to June 2022.Study EligibilityStudies evaluating the impact of COVID-19 on AMR in any population were included and influencing factors were extracted.MethodsPooling was done separately for Gram-negative and Gram-positive organisms. Random effects meta-analysis was performed.ResultsOf 6036 studies screened, 28 were included and 23 provided sufficient data for meta-analysis. The majority of studies focused on hospital settings (n=25, 89%). The COVID-19 pandemic was not associated with a change in the incidence density (IRR 0.99, 95% CI: 0.67 to 1.47) or proportion (RR 0.91, 95% CI: 0.55 to 1.49) of MRSA or VRE cases. A non-statistically significant increase was noted for resistant Gram-negatives (i.e., ESBL, CRE, MDR or carbapenem-resistant Pseudomonas or Acinetobacter species, IRR 1.64, 95% CI: 0.92 to 2.92; RR 1.08, 95% CI: 0.91 to 1.29). The absence of enhanced IPAC and/or ASP initiatives was associated with an increase in Gram-negative AMR (RR 1.11, 95%CI: 1.03 to 1.20), while studies that did report implementation of these initiatives noted no change in Gram-negative AMR (RR 0.80, 95%CI: 0.38 to 1.70). However, a test for subgroup differences showed no statistically significant difference between these groups (P=0.40)ConclusionThe COVID-19 pandemic could play an important role in the emergence and transmission of AMR, particularly for Gram-negative organisms in hospital settings. There is considerable heterogeneity in both the AMR metrics utilized and the rate of resistance reported across studies. These findings reinforce the need for strengthened infection prevention, antimicrobial stewardship, and AMR surveillance in the context of the COVID-19 pandemic.PROSPERO registration: CRD42022325831This research was carried out as part of routine work, no funding was received Data collection template, data, and analytic code are available upon request.
Verbosity with retelling: narrative discourse production in temporal lobe epilepsy
Authors: D’Aprano Fiore , Malpas Charles B. , Roberts Stefanie E. , Saling Michael M. 
Published: September 2022

AbstractThe conversational language of individuals with temporal lobe epilepsy (TLE) is circumstantial. The micro- and macrolinguistic underpinnings of this disturbance in narrative discourse, and the role of epilepsy and cognitive variables warrants exploration. We examined the elicited narrative output of 15 surgically-naïve individuals with TLE and 14 healthy controls. To replicate and extend Field and colleagues’ (2000) work, participants were shown an eight-frame cartoon Cowboy Story from Joanette and colleagues (1986) and were asked to produce five immediately consecutive elicitations of the narrative. Following transcription and coding, detailed multi-level discourse analysis demonstrated a typical pattern of compression across repetitions in controls. They produce increasingly concise and coherent output, reflective of a refined mental representation of the narrative, while individuals with TLE fail to do so. The narratives produced by individuals with TLE do not compromise the essential story components, although they are less informative overall: producing fewer novel units, and introducing more content that is repetitive, extraneous, and does not progress the narrative. Their narratives are ultimately less fluent, less cohesive, and less coherent relative to controls. Change across trials suggests that there are significant group by trial interactions in sample length, spontaneous duration, and total statements, which are not explained by seizure burden, age, or lexical retrieval deficits among those with TLE. These findings replicate the pattern of findings previously identified by Field and colleagues (2000), with novel insights into the macrolinguistic disturbances that characterise their narrative discourse over sequential repetitions. These findings suggest that individuals with TLE do not benefit from repeated engagement with a narrative in the same way that neurologically normal individuals do. We conclude that disturbances to social cognition and ultimately pragmatics in TLE might underpin inefficiencies in their communication.
Cardiac Magnetic Resonance Findings of COVID-19 Vaccine Associated Myocarditis at Intermediate Follow Up: a Comparison to Classic Myocarditis and MIS-C Related Myocarditis
Authors: Dove Matthew L. , Slesnick Timothy C. , Oster Matthew E. , Hashemi Sassan , Patel Trisha , Wilson Hunter C. 
Published: September 2022

ObjectiveTo report intermediate cardiac magnetic resonance (CMR) findings of COVID-19 vaccine associated myocarditis (C-VAM) and compare to classic myocarditis (CM) and multisystem inflammatory syndrome in children (MIS-C).Study DesignRetrospective cohort study including children diagnosed with C-VAM from 5/2021 through 12/2021 with early and intermediate CMR. Patients with CM and MIS-C with intermediate CMR were included for comparison.ResultsThere were 8 patients with C-VAM, 20 with CM, and 61 with MIS-C. Among those with C-VAM, CMR performed at median 3 days (IQR 3, 7) revealed 2/8 patients with left ventricular ejection fraction (LVEF)<55%, 7/7 patients with late gadolinium enhancement (LGE), and 5/8 patients with elevated native T1 values. Borderline T2 values suggestive of myocardial edema were present in 6/8. Follow-up CMRs performed at median 107 days (IQR 97, 177) showed normal ventricular systolic function, T1, and T2 values; 3/7 patients had LGE. At intermediate follow up the C-VAM group had a lower percentage of LVEF<55% compared to CM and MIS-C (0.0 vs 30.0 vs 6.6%, respectively, p=0.018) and an intermediate degree of LGE (42.9 vs 75.0 vs 3.3%, respectively, p<0.001). Pairwise comparisons showed fewer myocardial segments with LGE in the C-VAM group versus CM (4/119 vs 42/340, p=0.004) and more segments with LGE than MIS-C (4/119 vs 2/1020, p=0.0014).ConclusionPatients with C-VAM had no evidence of active inflammation or ventricular dysfunction on intermediate CMR although a minority had persistent LGE. Intermediate findings in C-VAM may be favorable compared to CM though LGE is more common compared to MIS-C.
Mucosal and systemic neutralizing antibodies to norovirus and rotavirus by oral immunization with recombinant rotavirus in infant mice
Authors: Kawagishi Takahiro , Sánchez-Tacuba Liliana , Feng Ningguo , Costantini Veronica P. , Tan Ming , Jiang Xi , Green Kim Y. , Vinjé Jan , Ding Siyuan , Greenberg Harry B. 
Published: September 2022

AbstractRotaviruses (RVs) preferentially replicate in the small intestine, frequently cause severe diarrheal disease, and following enteric infection generally induce variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not yet been experimentally tested as potential vaccine vectors to immunize against other gastrointestinal pathogens in vivo. This is a missed opportunity because several live-attenuated RV vaccines are already widely administered to infants and young children worldwide. To explore the feasibility of using RV as a dual vaccine vector, we rescued a replication-competent recombinant RRV harboring bicistronic gene segment 7 that encodes both the native RV NSP3 protein and a human norovirus (HuNoV) VP1 protein from the predominant genotype GII.4 (rRRV-HuNoV-VP1). The rRRV-HuNoV-VP1 expressed HuNoV VP1 in infected cells in vitro and importantly, elicited both systemic and local antibody responses to HuNoV following oral infection of suckling mice. Serum IgG and fecal IgA from infected suckling mice bound to and neutralized both RV and HuNoV. These findings have encouraging practical implications for the design of RV-based next-generation multivalent enteric vaccines to target HuNoV and other human enteric pathogens while providing immunity to RV.Significance statementMucosal immunity is a key component of protection against many pathogens. Robust and effective mucosal immune responses are generally induced following infection with a replication-competent pathogen at a mucosal surface. Several studies have attempted to develop viral vector-based enteric mucosal vaccines; however, the most advanced of these are still in clinical development. Here, we successfully induced systemic and mucosal antibody responses against both rotavirus and norovirus following inoculation of a recombinant rotavirus expressing the human norovirus major capsid protein. These responses are likely to correlate with protective immunity. Live-attenuated rotavirus vaccines have already proven safe and effective worldwide. These findings confirm the potential utility of using rotaviruses as a dual enteric vaccine platform for other important human enteric pathogens.
Opposite regulation of glycogen metabolism by cAMP produced in the cytosol and at the plasma membrane
Authors: Verhoeven Arthur J. , Bizerra Paulo F.V. , Gilglioni Eduardo H. , Go Simei , Li Hang Lam , Elferink Ronald P.J. Oude , Chang Jung-Chin 
Published: September 2022

SummaryCyclic AMP is produced in cells by two different types of adenylyl cyclases: at the plasma membrane by the transmembrane adenylyl cyclases (tmACs, ADCY1∼ADCY9) and in the cytosol by the evolutionarily more conserved soluble adenylyl cyclase (sAC, ADCY10). By employing high-resolution extracellular flux analysis to study glycogen breakdown in real time, we show here thatcAMP regulates glycogen metabolism in opposite directions depending on its location of synthesis within cells. While the canonical tmAC-cAMP-PKA axis promotes glycogenolysis, we demonstrate that the non-canonical sAC-cAMP-Epac1 signalling suppresses glycogenolysis in a variety of cell types. Our findings demonstrate the importance of cAMP microdomain organization in glycogen metabolism and reveal a novel role of sAC in energy metabolism during glucose deprivation.
gUMI-BEAR, a modular, unsupervised population barcoding method to track variants and evolution at high resolution
Authors: Rezenman Shahar , Knafo Maor , Tsigalnitski Ivgeni , Barad Shiri , Jona Ghil , Levi Dikla , Dym Orly , Reich Ziv , Kapon Ruti 
Published: September 2022

AbstractCellular lineage tracking provides a means to observe population makeup at the clonal level, allowing exploration of heterogeneity, evolutionary and developmental processes and individual clones’ relative fitness. It has thus contributed significantly to understanding microbial evolution, organ differentiation and cancer heterogeneity, among others. Its use, however, is limited because existing methods are highly specific, expensive, labour-intensive, and, critically, do not allow the repetition of experiments. To address these issues, we developed gUMI-BEAR (genomic Unique Molecular Identifier Barcoded Enriched Associated Regions), a modular, cost-effective method for tracking populations at high resolution. We first demonstrate the system’s application and resolution by applying it to track tens of thousands ofSaccharomyces cerevisiaelineages growing together under varying environmental conditions applied across multiple generations, revealing fitness differences and lineage-specific adaptations. Then, we demonstrate how gUMI-BEAR can be used to perform parallel screening of a huge number of randomly generated variants of theHsp82gene. We further show how our method allows isolation of variants, even if their frequency in the population is low, thus enabling unsupervised identification of modifications that lead to a behaviour of interest.