bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reward Responsiveness across Autism and Autistic Traits – Evidence from Neuronal, Autonomic, and Behavioural Levels
Authors: Matyjek Magdalena , Bayer Mareike , Dziobek Isabel 
Published: February 2022

AbstractAtypicalities in processing of social rewards have been suggested to lie at the root of social difficulties in autism spectrum conditions (ASC). While evidence for atypical reward function in ASC is mounting, it remains unclear whether it manifests specifically in hypo- or hyper-responsiveness, and whether it appears only in the social domain or more generally. Moreover, stimuli used as social rewards in studies often lack familiarity and relevance, which are known to enhance reward-related responses. In this study, we investigated behavioural (reaction times and ratings), neuronal (event-related potentials), and autonomic (pupil sizes) responses to three conditions – relevant social rewards, money, and neutral informative outcomes – in 26 ASC and 53 non-autistic subjects varying in levels of autistic traits, as measured with the Autism Spectrum Quotient (AQ). We used both a population-based approach (low AQ vs. high AQ) and a psychopathological approach (low AQ vs. ASC) to investigate the effects of both sub-clinical and clinical autistic traits on reward responsiveness. As hypothesised and preregistered, autism and autistic traits did not differently influence responses to social, monetary, and neutral outcomes on behavioural, neuronal or autonomic level. Although the ASC group rated the stimuli’s motivational and rewarding values lower than the other groups, the task performance was similar for all participants. Moreover, the ASC group in contrast to low AQ group showed enhanced brain responses (the CNV) in early anticipation and larger pupil constrictions in reward reception. Both effects were also predicted by autistic traits (AQ). Together, our results do not offer evidence for specifically social reward deficits in ASC. Instead, the data suggest enhanced neuronal and autonomic reward responsiveness linked to autism with simultaneously typical performance and reduced self-reported motivational and rewarding values of stimuli. Together, these results emphasise the need to investigate multiple processing levels for a broader picture of reward responsiveness in ASC.
Experimental and analytical framework for “mix-and-read” assays based on split luciferase
Authors: McArthur Nikki , Cruz-Teran Carlos , Thatavarty Apoorva , Reeves Gregory T. , Rao Balaji M. 
Published: February 2022

AbstractThe use of immunodetection assays including the widely used enzyme-linked immunosorbent assay (ELISA) in applications such as point-of-care detection is often limited by the need for protein immobilization and multiple binding and washing steps. Here, we describe an experimental and analytical framework for the development of simple and modular “mix-and-read” enzymatic complementation assays based on split luciferase that enable sensitive detection and quantification of analytes in solution. In this assay, two engineered protein binders targeting non-overlapping epitopes on the target analyte were each fused to non-active fragments of luciferase to create biosensor probes. Binding proteins to two model targets, lysozyme and Sso6904, were isolated from a combinatorial library of Sso7d mutants using yeast surface display. In the presence of the analyte, probes were brought into close proximity, reconstituting enzymatic activity of luciferase and enabling detection of low picomolar concentrations of the analyte by chemiluminescence. Subsequently, we constructed an equilibrium binding model that relates binding affinities of the binding proteins for the target, assay parameters such as the concentrations of probes used, and assay performance (limit of detection and concentration range over which the target can be quantified). Overall, our experimental and analytical framework provide the foundation for the development of split luciferase assays for detection and quantification of various targets.
Diversity begets diversity under microbial niche construction
Authors: Estrela Sylvie , Diaz-Colunga Juan , Vila Jean C.C. , Sanchez-Gorostiaga Alicia , Sanchez Alvaro 
Published: February 2022

AbstractMicrobial interactions are expected to modulate microbial diversity, but whether they inhibit or stimulate further diversity in complex microbial communities, and how, remains poorly understood. By assembling microbial communities in multiple identical habitats with a single limiting nutrient, here we provide direct evidence for the role of microbial niche construction and cross-feeding in driving a positive relationship between community diversity and focal lineage diversity in microbial communities. Combining these experiments with simulations, we show that this positive relationship is not inevitable but depends on the underlying metabolic structure of by-product secretions and uptake between different taxonomic levels.
scShapes: A statistical framework for identifying distribution shapes in single-cell RNA-sequencing data
Authors: Dharmaratne Malindrie , Kulkarni Ameya S , Fard Atefeh Taherian , Mar Jessica C 
Published: February 2022

AbstractBackgroundSingle cell RNA sequencing (scRNA-seq) methods have been advantageous for quantifying cell-to-cell variation by profiling the transcriptomes of individual cells. For scRNA-seq data, variability in gene expression reflects the degree of variation in gene expression from one cell to another. Analyses that focus on cell-cell variability therefore are useful for going beyond changes based on average expression and instead, identifying genes with homogenous expression versus those that vary widely from cell to cell.ResultsWe present a novel statistical framework scShapes for identifying differential distributions in single-cell RNA-sequencing data using generalized linear models. Most approaches for differential gene expression detect shifts in the mean value. However, as single cell data are driven by over-dispersion and dropouts, moving beyond means and using distributions that can handle excess zeros is critical. scShapes quantifies gene-specific cell-to-cell variability by testing for differences in the expression distribution while flexibly adjusting for covariates if required. We demonstrate that scShapes identifies subtle variations that are independent of altered mean expression and detects biologically-relevant genes that were not discovered through standard approaches.ConclusionsThis analysis also draws attention to genes that switch distribution shapes from a unimodal distribution to a zero-inflated distribution and raises open questions about the plausible biological mechanisms that may give rise to this, such as transcriptional bursting. Overall, the results from scShapes helps to expand our understanding of the role that gene expression plays in the transcriptional regulation of a specific perturbation or cellular phenotype. Our framework scShapes is incorporated into Bioconductor R package (https://github.com/Malindrie/scShapes).
Patterns of Polysubstance use among Adults in Malaysia – A Latent Class Analysis
Authors: Wan Shakira R.H , Tania Gyle R. L , Shubash S. G , Nur Liana A.M , Muhammad Fadhli MY 
Published: February 2022

AbstractIntroductionPolysubstance use is the use of more than one non-prescribed licit or illicit substance at one time. This is a common phenomenon, but little is known about the severity and the various substances used by adults in Malaysia.ObjectiveTo determine the pattern of polysubstance use and its associated factors among general adults in Malaysia.MethodologyThis was a secondary data analysis from the National Health and Morbidity Survey (NHMS) 2019), a cross-sectional population survey with a two-stage stratified random sampling design. A total of 10,472 Malaysians aged 18 years and above participated in this survey. Polysubstance use was defined as concurrent use of more than one substance, either alcohol, tobacco, or drugs (opioid, marijuana, amphetamine/ methamphetamine or kratom). A latent class analysis (LCA) was used to identify the membership of polysubstance groups. The association of class membership with demographic profiles was examined using Multinomial Logistic Regression analysis.ResultsFit indices (AIC =16458.9, BIC = 16443.6) from LCA supported 3 classes solution: i) Combination of tobacco and alcohol (Tob+Alc) use (2.4%), ii) multi-drug use including kratom (0.3%) and iii) non/negligible user (97.3%). The multinomial model showed young adults (18-40 years) had a higher likelihood of being polysubstance users both for Tob+Alc class (OR=4.1) and multi-drug class (OR=3.9) compared to older age (≥60 years). Chinese (OR = 18.9), Indian (OR =23.3), Indigenous Sabah & Sarawak (OR =34.6) and others ethnicity (OR =8.9) showed higher odds of being Tob+Alc users than Malays. The greater odds of Tob+Alc. use for male (OR =35.5), working group (OR =1.5) and low education level group (OR=3.2).ConclusionOur study highlights patterns and demographics related to the use of polysubstance among adults in Malaysia. These results would help formulate specific prevention programmes for these high risk groups.
Interpretation of southern hemisphere humpback whale diet via stable isotopes; implications of tissue-specific analysis
Authors: Eggebo June , Groβ Jasmin , Bengtson Nash Susan 
Published: February 2022

AbstractBlubber and skin are commonly used tissues in stable isotope analysis for the purpose of investigating cetacean diet. Critical comparison of tissue-specific isotopic signals is, however, lacking resulting in uncertainty surrounding the representativeness and therefore utility of different tissues for accurate determination of recent foraging. This study used remotely biopsied blubber and skin tissues from southern hemisphere humpback whales for strategic comparison of δ13C and δ15N values. Samples were collected 2008-2018 as part of long-term monitoring under the Humpback Whale Sentinel Program. Blubber tissues were lipid-extracted prior to analysis, whilst mathematical lipid-correction was performed on skin samples. Isotopic values from paired blubber and skin samples from the same individuals were compared to assess whether tissues could be used interchangeably for isotope analysis and dietary interpretation. Significant differences were observed for both δ13C and δ15N, flagging previously undocumented methodological considerations, and the need for method validation and standardisation in application of these approaches. This study therefore advances methodological aspects of cetacean dietary analysis. This is of elevated importance in the context of rapidly changing ocean ecosystems.
uniPort: a unified computational framework for single-cell data integration with optimal transport
Authors: Cao Kai , Gong Qiyu , Hong Yiguang , Wan Lin 
Published: February 2022

AbstractSingle-cell data integration can provide a comprehensive molecular view of cells. Here we introduce uniPort, a unified single-cell data integration framework which combines a coupled Variational Autoencoder (coupled-VAE) and Minibatch Unbalanced Optimal Transport (Minibatch-UOT). It leverages both highly variable common and dataset-specific genes for integration and is scalable to large-scale and partially overlapping datasets. uniPort jointly embeds heterogeneous single-cell multi-omics datasets into a shared latent space. It can further construct a reference atlas for online prediction across datasets. Meanwhile, uniPort provides a flexible label transfer framework to deconvolute spatial heterogeneous data using optimal transport space, instead of embedding latent space. We demonstrate the capability of uniPort by integrating a variety of datasets, including single-cell transcriptomics, chromatin accessibility and spatially resolved transcriptome data. uniPort software is available athttps://github.com/caokai1073/uniPort.
Lung evolution in vertebrates and the water-to-land transition
Authors: Cupello Camila , Hirasawa Tatsuya , Tatsumi Norifumi , Yabumoto Yoshitaka , Gueriau Pierre , Isogai Sumio , Matsumoto Ryoko , Saruwatari Toshiro , King Andrew , Hoshino Masato , Uesugi Kentaro , Okabe Masataka , Brito Paulo M. 
Published: February 2022

AbstractA crucial evolutionary change in vertebrate history was the Palaeozoic (Devonian ~400 million years ago) water-to-land transition, allowed by key morphological and physiological modifications including the acquisition of lungs. Nonetheless, the origin and early evolution of vertebrate lungs remain highly controversial, particularly whether the ancestral state was paired or unpaired. Due to the rarity of fossil soft tissue preservation, lung evolution can only be traced based on the extant phylogenetic bracket. Here we investigate, for the first time, lung morphology in extensive developmental series of key living lunged osteichthyans using synchrotron X-ray microtomography and histology. Our results shed light on the primitive state of vertebrate lungs as unpaired, evolving to be truly paired in the lineage towards the tetrapods. The water-to-land transition confronted profound physiological challenges and paired lungs were decisive for increasing the surface area and the pulmonary compliance and volume, especially during the air-breathing on land.
The exchange rates of amide and arginine guanidinium CEST in the mouse brain
Authors: Wang Kexin , Sui Ran , Chen Lin , Li Yuguo , Xu Jiadi 
Published: February 2022

AbstractPurposeTo develop a pipeline for measuring the exchange rates and concentrations of in vivo excgangeable protons, and to demonstrate this for the amide and arginine (Arg) guanidinium (Guan) protons in mobile proteins in the mouse brain.MethodsAn ultra-short echo (UTE) CEST sequence with a continuous wave presaturation (preRadCEST) was applied to acquire Z-spectra with robustness to motion and physiological fluctuations. AmideCEST and Arginine guanCEST (ArgCEST) were extracted and their proton concentrations and exchange rates obtained using a two-step multi-B1Bloch fitting approach that included the semisolid macromolecular background. To minimize contamination from the amine protons from creatine and phosphocreatine, ArgCEST measurements were performed on the Guanidinoacetate N-methyltransferase deficiency (GAMT-/-) mouse characterized by low creatine and phosphocreatine concentrations in the brain.ResultsFor the amideCEST proton pool, the exchange rate and concentrations were found to be 59.6 ± 9.0 s-1and 41.7 ± 7.0 mM, respectively, with the maximum signal observed at B1= 0.8 μT. For the ArgCEST proton, the guanidinium exchange these were 70.1 ± 5.5 s-1and 10.1 ± 1.3 mM, respectively, with the maximum effect observed at B1= 0.9 μT. The current study suggests that the inverse pH dependence in GuanCEST of brain is led by the CrCEST component, not ArgCEST.ConclusionThe current pipeline is expected to have general use forin vivoCEST quantitation and optimization of visible CEST resonances.
A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants
Authors: Farley Scotland E. , Kyle Jennifer E. , Leier Hans C. , Bramer Lisa M. , Weinstein Jules , Bates Timothy A. , Lee Joon-Yong , Metz Thomas O. , Schultz Carsten , Tafesse Fikadu G. 
Published: February 2022

AbstractA comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. We mapped alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics. We found that SARS-CoV-2 rewires host lipid metabolism, altering 409 lipid species up to 64-fold relative to controls. We correlated these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We found that lipid droplet plasticity is a key feature of infection and that viral propagation can be blocked by small-molecule glycerolipid biosynthesis inhibitors. We found that this inhibition was effective against the main variants of concern (alpha, beta, gamma, and delta), indicating that glycerolipid biosynthesis is a conserved host dependency factor that supports this evolving virus.
Structural model of microtubule dynamics inhibition by Kinesin-4 from the crystal structure of KLP-12 –tubulin complex
Authors: Taguchi Shinya , Nakano Juri , Imasaki Tsuyoshi , Kita Tomoki , Saijo-Hamano Yumiko , Sakai Naoki , Shigematsu Hideki , Okuma Hiromichi , Shimizu Takahiro , Nitta Eriko , Kikkawa Satoshi , Mizobuchi Satoshi , Niwa Shinsuke , Nitta Ryo 
Published: February 2022

AbstractKinesin superfamily proteins are microtubule-based molecular motors driven by the energy of ATP hydrolysis. Among them, the kinesin-4 family is a unique motor that inhibits microtubule dynamics. Although mutations of kinesin-4 cause several diseases, its molecular mechanism is unclear because of the difficulty of visualizing the high-resolution structure of kinesin-4 working at the microtubule plus-end. Here, we report that KLP-12, a C. elegans kinesin-4 ortholog of KIF21A and KIF21B, is essential for proper length control of C. elegans axons, and its motor domain represses microtubule polymerization in vitro. The crystal structure of the KLP-12 motor domain complexed with tubulin, which represents the high-resolution structural snapshot of inhibition state of microtubule-end dynamics, revealed the bending effect of KLP-12 for tubulin. Comparison with the KIF5B-tubulin and KIF2C-tubulin complexes, which represent the elongation and shrinking forms of microtubule ends, respectively, showed the curvature of tubulin introduced by KLP-12 is in between them. Taken together, KLP-12 controls the proper length of axons by modulating the curvature of the microtubule ends to inhibit the microtubule dynamics.
Strong phylogenetic and ecological effects on host competency for avian influenza in Australian wild birds
Authors: Wille Michelle , Lisovski Simeon , Roshier David , Ferenczi Marta , Hoye Bethany J. , Leen Trent , Warner Simone , Fouchier Ron A. M. , Hurt Aeron C. , Holmes Edward C. , Klaassen Marcel 
Published: February 2022

AbstractHost susceptibility to parasites is mediated by intrinsic and external factors such as genetics, age or season. While key features have been revealed for avian influenza A virus (AIV) in waterfowl of the Northern Hemisphere, the role of host phylogeny has received limited attention. Herein, we analysed 12339 oropharyngeal and cloacal swabs and 10826 serum samples collected over 11 years from wild birds in Australia. As well as describing species-level differences in prevalence and seroprevalence, we reveal that host phylogeny is a key driver in susceptibility. We confirm the role of age in AIV seroprevalence and viral prevalence. Seasonality effects appear less pronounced than in the Northern Hemisphere, while annual variations are potentially linked to El Niño– Southern Oscillation. Taken together, our study provides new insights into evolutionary ecology of AIV in its avian hosts, defining distinctive processes on the continent of Australia and expanding our understanding of AIV globally.
4th Dose COVID mRNA Vaccines’ Immunogenicity & Efficacy Against Omicron VOC
Authors: Regev-Yochay Gili , Gonen Tal , Gilboa Mayan , Mandelboim Michal , Indenbaum Victoria , Amit Sharon , Meltzer Lilac , Asraf Keren , Cohen Carmit , Fluss Ronen , Biber Asaf , Nemet Ital , Kliker Limor , Joseph Gili , Doolman Ram , Mendelson Ella , Freedman Laurence S. , Harats Dror , Kreiss Yitshak , Lustig Yaniv 
Published: February 2022

AbstractBACKGROUNDFollowing the emergence of the Omicron variant of concern, we investigated immunogenicity, efficacy and safety of BNT162b2 or mRNA1273 fourth dose in an open-label, clinical intervention trial.METHODSPrimary end-points were safety and immunogenicity and secondary end-points were vaccine efficacy in preventing SARS-CoV-2 infections and COVID-19 symptomatic disease. The two intervention arms were compared to a matched control group. Eligible participants were healthcare-workers (HCW) vaccinated with three BNT162b2 doses, and whose IgG antibody levels were ≤700 BAU (40-percentile). IgG and neutralizing titers, direct neutralization of live VOCs, and T-cell activation were assessed. All participants were actively screened for SARS-CoV-2 infections on a weekly basis.RESULTSOf 1050 eligible HCW, 154 and 120 were enrolled to receive BNT162b2 and mRNA1273, respectively, and compared to 426 age-matched controls. Recipients of both vaccine types had a ∼9-10-fold increase in IgG and neutralizing titers within 2 weeks of vaccination and an 8-fold increase in live Omicron VOC neutralization, restoring titers to those measured after the third vaccine dose. Breakthrough infections were common, mostly very mild, yet, with high viral loads. Vaccine efficacy against infection was 30% (95%CI:-9% to 55%) and 11% (95%CI:-43% to +43%) for BNT162b2 and mRNA1273, respectively. Local and systemic adverse reactions were reported in 80% and 40%, respectively.CONCLUSIONSThe fourth COVID-19 mRNA dose restores antibody titers to peak post-third dose titers. Low efficacy in preventing mild or asymptomatic Omicron infections and the infectious potential of breakthrough cases raise the urgency of next generation vaccine development.Trial registration numberclicaltrials.gov: NCT05231005, NCT05230953
Urinary collagen-derived peptides as sensitive markers for bone resorption and bisphosphonate treatment in kidney transplant patients
Authors: Marx David , Anglicheau Dany , Caillard Sophie , Moulin Bruno , Kochman Audrey , Mischak Harald , Pejchinowski Martin , Latosinska Agnieszka , Bienaimé Frank , Prié Dominique , Marquet Pierre , Perrin Peggy , Gwinner Wilfried , Metzger Jochen 
Published: February 2022

AbstractKidney transplant recipients (KTR) are at increased risk of fractures. Total urinary hydroxyproline excretion used to be a marker for bone resorption (BR) but faded into the background when more specific markers like Beta-CrossLaps (CTX) became available. Proteomic studies identified numerous hydroxyproline-containing urinary collagen peptides but their origin remains unknown. We followed the hypothesis that some of the urinary collagen peptides are associated with BR and are markers for pathophysiological changes in bone metabolism of KTR. Clinical and laboratory data including serum levels of CTX in 96 KTR from two French centers (Strasbourg, n=38; Paris-Necker, n=58) were correlated with the signal intensity of urinary peptides identified by capillary electrophoresis (CE) coupled to mass spectrometry (MS) and tandem-MS. The effect of oral bisphosphonates on urinary peptides was studied in an independent group of 11 KTR. Eighty-two urinary peptides were identified to be significantly correlated with serum CTX levels in both cohorts. Statistical association with parameters other than BR markers were not significant. Collagen α-1(I) chain (COL1A1) was the most frequently identified peptide source. COL1A1 peptides associated with BR were significantly more hydroxylated than those showing no association (55.9% versus 45,2%, p<0.0003 by a χ2-test). From the 82 urinary peptides correlated to CTX, 17 were significantly associated with bisphosphonate treatment. All of these 17 peptides showed a marked reduction in their excretion levels after 410 ± 344 days of bisphosphonate treatment compared to baseline levels. We studied the cleavage sites of these COL1A1 peptides and observed a signature of Cathepsin K and Matrix Metallopeptidase 9. This study provides strong evidence for the occurrence of collagen peptides in the urine of KTR that are associated with BR and that are sensitive to bisphosphonate treatment. Their assessment might become a valuable tool to monitor bone status in KTR.