bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profile analysis in listeners with sensorineural hearing loss
Authors: Guest Daniel R. , Cameron David A. , Schwarz Douglas M. , Leong U-Cheng , Carney Laurel H. 
Published: December 2023

ABSTRACTMany sounds contain spectral modulations at multiple scales, but much is still unknown about how such spectral features are represented in the auditory system. One behavioral task that provides insight into this question is profile analysis. In a typical profile-analysis task, listeners are asked to discriminate between a complex tone with equal-amplitude components and a complex tone with a single incremented component. Because listeners can perform profile analysis even when the overall sound level of the stimuli is randomized from interval to interval, this task is thought to be a useful index of relative processing of spectral shape, rather than just sensitivity to absolute level changes. Here, we measured profile analysis across the frequency range in a group of listeners that varied widely in their hearing status. We then modeled the resulting behavioral data by decoding responses to the stimuli from computational models of the auditory nerve and inferior colliculus. We found that both hearing loss at the target frequency and increases in the target frequency were associated with poorer profile-analysis thresholds, and that these results could both be explained as the result of corresponding changes in sensitivity of temporal modulation-sensitive cells at the level of the inferior colliculus. These results suggest that key features of profile-analysis may reflect the limits of central neural tuning to temporal modulations.
Developmental remodeling repurposes larval neurons for sexual behaviors in adultDrosophila
Authors: Diamandi Julia A. , Duckhorn Julia C. , Miller Kara E. , Weinstock Mason , Leone Sofia , Murphy Micaela R. , Shirangi Troy R. 
Published: December 2023

SUMMARYMost larval neurons inDrosophilaare repurposed during metamorphosis for functions in adult life, but their contribution to the neural circuits for sexually dimorphic behaviors is unknown. Here, we identify two interneurons in the nerve cord of adultDrosophilafemales that control ovipositor extrusion, a courtship rejection behavior performed by mated females. We show that these two neurons are present in the nerve cord of larvae as mature, sexually monomorphic interneurons. During pupal development, they acquire the expression of the sexual differentiation gene,doublesex, undergodoublesex-dependent programmed cell death in males, and are remodeled in females for functions in female mating behavior. Our results demonstrate that the neural circuits for courtship inDrosophilaare built in part using neurons that are sexually reprogrammed from former sex-shared activities in larval life.
Seasonally increasing parasite load is associated with microbiome dysbiosis in wild bumblebees
Authors: Young Mark G. , Just Josefine , Lee Ye Jin , McMahon Thomas , Gonzalez James , Noh Suegene , Angelini David R. 
Published: December 2023

AbstractThe microbiome is increasingly recognized for its complex relationship with host fitness. Bumblebees are host to a characteristic gut microbiome community that is derived and reinforced through social contact between individuals. The bumblebee microbiome is species-poor, and primarily composed from a small number of core taxa that are associated with the greater tribe of corbiculate bees. Experimental findings support a role for the core bumblebee microbiome in resistance to severe infections by a common trypanosomal parasite,Crithidia bombi. However, most studies have been small in scale, often considering just one or two bumblebee species, or making use of commercially-reared bees. To better understand the microbiome diversity of wild populations, we have deeply sampled field populations of ten sympatric species found throughout central and down east Maine in a three-year microbiome field survey. We have used 16S amplicon sequencing to produce microbiome community profiles, and qPCR to screen samples for infections byCrithidia bombi. The breadth of our dataset has enabled us to test for seasonal and interspecific trends in the microbiome community. Controlling for these external sources of variation, we have identified microbial factors associated with infection and parasite load that support the role of the core microbiome in resistance to severe infection.
Cyclase-associated protein is a pro-formin anti-capping processive depolymerase of actin barbed and pointed ends
Authors: Towsif Ekram M. , Shekhar Shashank 
Published: December 2023

SummaryCellular actin networks display distinct assembly and disassembly dynamics resulting from multicomponent reactions occurring primarily at the two ends and the sides of actin filaments [1–3]. While barbed ends are considered the hotspot of actin assembly [4], disassembly is thought to primarily occur via reactions on filament sides and pointed ends [3, 5–11]. Cyclase-associated protein (CAP) has emerged as the main protagonist of actin disassembly and remodeling – it collaborates with cofilin to increase pointed-end depolymerization by 300-fold [6, 7], promotes filament “coalescence” in presence of Abp1 [12], and accelerates nucleotide exchange to regenerate monomers for new rounds of assembly [13–15]. CAP has also been reported to enhance cofilin-mediated severing [16, 17], but these claims have since been challenged [7]. Using microfluidics-assisted three-color single-molecule imaging, we now reveal that CAP also has important functions at filament barbed ends. We reveal that CAP is a processive barbed-end depolymerase capable of tracking both ends of the filament. Each CAP binding event leads to removal of about 5,175 and 620 subunits from the barbed and pointed ends respectively. We find that the WH2 domain is essential, and the CARP domain is dispensable for barbed-end depolymerization. We show that CAP co-localizes with barbed-end bound formin and capping protein, in the process increasing residence time of formin by 10-fold and promoting dissociation of CP by 4-fold. Our barbed-end observations combined with previously reported activities of CAP at pointed ends and sides, firmly establish CAP as a key player in actin dynamics.
Simultaneous CRISPR screening and spatial transcriptomics reveals intracellular, intercellular, and functional transcriptional circuits
Authors: Binan Loϊc , Danquah Serwah , Valakh Vera , Simonton Brooke , Bezney Jon , Nehme Ralda , Cleary Brian , Farhi Samouil L 
Published: December 2023

AbstractPooled optical screens have enabled the study of cellular interactions, morphology, or dynamics at massive scale, but have not yet leveraged the power of highly-plexed single-cell resolved transcriptomic readouts to inform molecular pathways. Here, we present Perturb-FISH, which bridges these approaches by combining imaging spatial transcriptomics with parallel optical detection ofin situamplified guide RNAs. We show that Perturb-FISH recovers intracellular effects that are consistent with Perturb-seq results in a screen of lipopolysaccharide response in cultured monocytes, and uncover new intercellular and density-dependent regulation of the innate immune response. We further pair Perturb-FISH with a functional readout in a screen of autism spectrum disorder risk genes, showing common calcium activity phenotypes in induced pluripotent stem cell derived astrocytes and their associated genetic interactions and dysregulated molecular pathways. Perturb-FISH is thus a generally applicable method for studying the genetic and molecular associations of spatial and functional biology at single-cell resolution.
Safety and feasibility of a combined neuromodulation and yoga intervention for individuals with mild traumatic brain injury and chronic pain: a pilot study
Authors: Krese Kelly , Aaronson Alexandra , Donnelly Kyla Z , Shah Rachana , Chaudhuri Sarmistha , Bobra Sonia , Etingen Bella , Bedo Sabrina , Kale Ibuola , Billups Andrea , Colletta Kalea , Kletzel Sandra , Kemp Amy , Bender Pape Theresa L , Bhaumik Dulal , Herrold Amy A 
Published: December 2023

AbstractThe complex clinical presentation of patients with mild traumatic brain injury and chronic pain (mTBI+CP) often causes symptoms that are resistant to standard treatments. For the first time, our team combined intermittent theta burst stimulation and yoga (iTBS+LYB) to maximize treatment effect and promote functional recovery in a pilot open-label clinical trial among Veterans with mTBI+CP. A 3-minute iTBS protocol was delivered including 3 pulses of stimulation given at 50Hz, repeated every 200ms at 80% of the resting MT, with an inter-pulse-interval of 20ms. A 2s train of iTBS was repeated every 10s for a total of 190s, for a total of 600 pulses. After all participants received iTBS, a certified yoga instructor guided a 90-minute group LYB session. N=19 participants were enrolled; 71.4% (10/14) completed all 6 iTBS+LYB sessions. Three individuals experienced headaches, a known side effect of iTBS, which resulted in one participant self-withdrawing. iTBS+LYB for mTBI+CP is feasible and safe, with known side effects.
Dual T-cell constant β chain (TRBC)1 and TRBC2 staining for the identification of T-cell neoplasms by flow cytometry
Authors: Horna Pedro , Weybright Matthew J , Ferrari Mathieu , Jungherz Dennis , Peng YaYi , Akbar Zulaikha , Ilca F Tudor , Otteson Gregory E , Seheult Jansen N , Ortmann Janosch , Shi Min , Maciocia Paul M , Herling Marco , Pule Martin A , Olteanu Horatiu 
Published: December 2023

ABSTRACTThe diagnosis of leukemic T-cell malignancies is often challenging, due to overlapping features with reactive T-cells and limitations of currently available T-cell clonality assays. Recently developed therapeutic antibodies specific for the mutually exclusive T-cell receptor constant β chain (TRBC)1 and TRBC2 isoforms provide a unique opportunity to assess for TRBC-restriction as a surrogate of clonality in the flow cytometric analysis of T-cell neoplasms. To demonstrate the diagnostic utility of this approach, we studied 135 clinical specimens with (50) or without (85) T-cell neoplasia, in addition to 29 blood samples from healthy donors. Dual TRBC1 and TRBC2 expression was studied within a comprehensive T-cell panel, in a fashion similar to the routine evaluation of kappa and lambda immunoglobulin light chains for the detection of clonal B-cells. Polytypic TRBC expression was demonstrated on total, CD4+and CD8+T-cells from all healthy donors; and by intracellular staining on benign T-cell precursors. All neoplastic T-cells were TRBC-restricted, except for 5 cases (10%) lacking TRBC expression. T-cell clones of uncertain significance were identified in 15 samples without T-cell malignancy (13%), and accounted for smaller subsets than neoplastic clones (median: 4.7% vs. 73% of lymphocytes, p<0.0001). Single staining for TRBC1 produced spurious TRBC1-dim subsets in 21 clinical specimens (16%), all of which resolved with dual TRBC1/2 staining. Assessment of TRBC restriction by flow cytometry provides a rapid diagnostic method to detect clonal T-cells, and to accurately determine the targetable TRBC isoform expressed by T-cell malignancies.
Prediction of Metastatic Site Based On Somatic Gene Mutations in Primary Tumors in Prostate Cancer
Authors: Gomez Paul 
Published: December 2023

ABSTRACTObjectiveThe goal of this research is to predict the most likely metastatic site(s) of a primary prostate cancer tumor that has been resected via radical prostatectomy; its genome has been sequenced to obtain a list of gene mutations; and after initial inspection of pelvic lymph nodes, there is no clinical evidence of metastasis. However, micrometastases might already be growing in distant organs and cannot be detected at the time of surgery.BackgroundThe most common metastatic targets in prostate cancer (PCa) are the pelvic lymph nodes (PLN) and bones. The PLNs are routinely dissected by a procedure called pelvic lymph node dissection (PLND) simultaneously with the surgical removal of the prostate to detect the presence of metastatic growths. Additionally, the prostate-specific antigen (PSA) level is used to assess the existence of a metastatic stage. However, micrometastases in other organs and tissues might be overlooked.MethodsWe downloaded publicly available prostate cancer tumor data from the websitewww.CbioPortal.org.After choosing the 25 most commonly mutated genes by metastatic site (MS) and finding genes that are uniquely mutated on specific metastatic sites, we found that the mutational signature of a prostate cancer tumor is associated with its MS, and thus, we developed a method to numerically predict this association.ResultsAfter executing a computational algorithm on the data set of metastatic prostate tumors, it was found that we can predict metastatic sites with the following accuracies: bone (90.9%), retroperitoneum (87.5%), liver (83.0%), kidney (80.0%), pancreas (80.0%), adrenal glands (75.0%), lung (71.1%), and brain (72.5%).ConclusionsWe successfully developed a method and an algorithm that predict the most likely metastatic site of a primary prostate cancer tumor based on its genetic mutations. The accuracy of the predictions for eight metastatic sites ranges from 71.1% to 90.9%, with an average of 80.5%.
Small RNAs in plasma extracellular vesicles define biomarkers of premanifest changes in Huntington’s disease
Authors: Herrero-Lorenzo Marina , Pérez-Pérez Jesús , Escaramís Georgia , Martínez-Horta Saül , Pérez-González Rocío , Rivas-Asensio Elisa , Kulisevsky Jaime , Gámez-Valero Ana , Martí Eulàlia 
Published: December 2023

AbstractDespite the advances in the understanding of Huntington’s disease (HD), there is the need for molecular biomarkers to categorize mutation-carriers during the preclinical stage of the disease preceding the functional decline. Small RNAs (sRNAs) are a promising source of biomarkers since their expression levels are highly sensitive to pathobiological processes. Here, using an optimized method for plasma extracellular vesicles (EVs) purification and an exhaustive analysis pipeline of sRNA sequencing data, we show that EV-sRNAs are early downregulated in mutation-carriers, and that this deregulation is associated with premanifest cognitive performance. Seven candidate sRNAs (tRF-Glu-CTC, tRF-Gly-GCC, miR-451a, miR-21-5p, miR-26a-5p, miR-27a-3p, and let7a-5p) were validated in additional subjects, showing a significant diagnostic accuracy at premanifest stages. Of these, miR – 21-5p was significantly decreased over time in a longitudinal study; and miR-21-5p and miR-26a-5p levels correlated with cognitive changes in the premanifest cohort. In summary, the present results suggest that deregulated plasma EV-sRNAs define an early biosignature in mutation carriers with specific species sensing the progression and cognitive changes occurring at the premanifest stage.
Brain network dynamics predict moments of surprise across contexts
Authors: Zhang Ziwei , Rosenberg Monica D. 
Published: December 2023

AbstractWe experience surprise when reality conflicts with our expectations. When we encounter such expectation violations in psychological tasks and daily life, are we experiencing completely different forms of surprise? Or is surprise a fundamental psychological process with shared neural bases across contexts? To address this question, we identified a brain network model, the surprise edge-fluctuation-based predictive model (EFPM), whose regional interaction dynamics measured with functional magnetic resonance imaging (fMRI) predicted surprise in an adaptive learning task. The same model generalized to predict surprise as a separate group of individuals watched suspenseful basketball games and as a third group watched videos violating psychological expectations. The surprise EFPM also uniquely predicts surprise, capturing expectation violations better than models built from other brain networks, fMRI measures, and behavioral metrics. These results suggest that shared neurocognitive processes underlie surprise across contexts and that distinct experiences can be translated into the common space of brain dynamics.
Non-coding rare variant associations with blood traits on 166 740 UK Biobank genomes
Authors: Ribeiro Diogo M. , Delaneau Olivier 
Published: December 2023

AbstractLarge biobanks with whole-genome sequencing now enable the association of non-coding rare variants with complex human traits. Given that >98% of the genome is available for exploration, the selection of non-coding variants remains a critical yet unresolved challenge in these analyses. Here, we leverage knowledge of blood gene regulation and deleteriousness scores to select non-coding variants pertinent for association with blood-related traits. We leverage whole genome sequencing and 59 blood cell count and biomarker measurements for 166 740 UK Biobank samples to perform variant collapsing tests. We identified hundreds of gene-trait associations involving non-coding variants across the 59 traits. However, we demonstrate that the majority of these non-coding rare variant associations (i) reproduce associations known from common variant studies and (ii) are driven by linkage disequilibrium between nearby common and rare variants. This study underscores the prevailing challenges in rare variant analysis and the need for caution when interpreting non-coding rare variant association results.
Humans progressively feel agency over events triggered before they act
Authors: Toma Marcus , Mattout Jérémie , Quentin Romain , Rassoulou Fayed , Gautier Alice , Maby Emmanuel , Vernet Marine 
Published: December 2023

AbstractArtificial Intelligence (AI) has become increasingly efficient in anticipating our behavior. Will this impact, in the near future, how much we feel control over events generated with AI-assistance? This would in turn influence our decisions, actions, mental health and sense of responsibility. In everyday life, our sense of agency over events occurring at various delays after our actions has adapted to accommodate these delays. Here, we investigate whether our sense of agency can also adapt to an unusual situation where a consequence precedes an action. We used an online game in which players aimed to beat the computer at finding and clicking on a target to trigger an animation, while, in fact, an algorithm triggered the animation before the players’ click. The animation was not randomly controlled by the algorithm, but rather based on the history of the players’ past movements and on the beginning of their current movement. We used correlational, machine learning decoding, and modelling approaches to capture how players compute their reported sense of agency over the animation. We found evidence that, in less than an hour, players implicitly learned that the timing of the animation was related to their own actions, and adapted their sense of agency accordingly. Such findings may help us to anticipate how humans will integrate AI-assistance to guide their behavior.
Length–weight relationships of the French pikesEsoxspp (Teleostei, Esocidae)
Authors: Royer Lucas , Teletchea Fabrice , Delavergne Sophie , Lafitte Frédéric , Escarpit Marion , Molina Quentin , Breugnot Emilie , Cosson Eddy , L’Hostis Aurélia , Denys Gaël P.J. 
Published: December 2023

AbstractLength–weight relationships for PikeEsox aquitanicusandEsox luciusfrom France are provided. A total of 9,070 specimens were collected, measured and weighted from 1981 to 2022 throughout France by Departmental Angling Federations and the French Biodiversity Agency during their survey by electrofishing. For all species, the values ofbare 2.960 forE. aquitanicusand 2.987 forEsox lucius. We hypothetize this difference by the poor environment where live the Aquitanian pike with no abundant available food and small prey fish species which do not contribute to good conditions for the growth. The study provides the first reference of length–weight relationships forE. aquitanicus.
Age-related changes in human skeletal muscle transcriptome and proteome are more affected by chronic inflammation and physical inactivity than primary aging
Authors: Kurochkina Nadia S. , Orlova Mira A. , Vigovskiy Maksim A. , Zgoda Viktor G. , Vepkhvadze Tatiana F. , Vavilov Nikita E. , Makhnovskii Pavel A. , Grigorieva Olga A. , Boroday Yakov R. , Philippov Vladislav V. , Lednev Egor M. , Efimenko Anastasia Yu. , Popov Daniil V. 
Published: December 2023

AbstractEvaluation of the influence of primary and secondary aging on the manifestation of molecular and cellular hallmarks of aging is a challenging and currently unresolved issue. Our study represents the first demonstration of the distinct role of primary aging and chronic inflammation/physical inactivity – the most important drivers of secondary aging, in the regulation of transcriptomic and proteomic profiles in human skeletal muscle. To achieve this purpose, young healthy people (n=15), young (n=8) and older (n=37) patients with knee/hip osteoarthritis, a model to study the effect of long-term inactivity and chronic inflammation on the vastus lateralis muscle, were included in the study. It was revealed that widespread and substantial age-related changes in gene expression in older patients relative to young healthy people (∼4,000 genes regulating mitochondrial function, proteostasis, cell membrane, secretory and immune response) were related to the long-term physical inactivity and chronic inflammation rather than primary aging. Primary aging contributed mainly to the regulation of genes (∼200) encoding nuclear proteins (regulators of DNA repair, RNA processing, and transcription), mitochondrial proteins (genes encoding respiratory enzymes, mitochondrial complex assembly factors, regulators of cristae formation and mitochondrial reactive oxygen species production), as well as regulators of proteostasis. It was found that proteins associated with aging were regulated mainly at the post-transcriptional level. The set of putative primary aging genes and their potential transcriptional regulators can be used as a resource for further targeted studies investigating the role of individual genes and related transcription factors in the emergence of a senescent cell phenotype.
Do electromagnetic fields from subsea power cables effect elasmobranch behaviour? A risk-based approach for the Dutch Continental Shelf
Authors: Hermans Annemiek , Winter Hendrik V. , Gill Andrew B. , Murk Albertinka J. 
Published: December 2023

AbstractSubsea power cables cause electromagnetic fields (EMFs) into the marine environment. Elasmobranchs (rays, skates, sharks) are particularly sensitive to EMFs as they use electromagnetic-receptive sensory systems for orientation, navigation and locating conspecifics or buried prey. Cables may intersect with egg laying sites, foraging habitat and migration routes of elasmobranchs and the effects of encountering EMFs on species of elasmobranchs are largely unknown. Demonstrated behavioural effects are attraction, disturbance and indifference, depending on EMF characteristics, exposed life stage, exposure level and duration. We estimated exposure levels of elasmobranchs to subsea cable EMFs, based on modelled magnetic fields in the Dutch Continental Shelf and compared these to reported elasmobranch sensory sensitivity ranges and experimental effect levels. We conclude that the risk from subsea power cables has a large uncertainty and varies per life stage and species ecology. Based on estimated no-observed effect levels (from 10-3to 10-1µT) we discuss what will probably be the most affected species and life stage for six common benthic elasmobranchs in the Southern North Sea. We identify critical knowledge gaps for reducing the uncertainty in the risk assessments for EMFs effects on elasmobranchs.