bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spns1-dependent endocardial lysosomal function drives valve morphogenesis through Notch1-signaling
Authors: Chávez Myra N. , Arora Prateek , Ernst Alexander , Meer Marco , Morales Rodrigo A. , Mercader Nadia 
Published: March 2024

AbstractAutophagy-lysosomal degradation is an evolutionarily conserved process key to cellular homeostasis, differentiation, and stress survival, which is particularly important for the cardiovascular system. Furthermore, experimental and clinical observations indicate it affects cardiac morphogenesis, including valve development. However, the cell-specificity and functional role of autophagic processes during heart development remain unclear. Here, we introduce novel zebrafish models to visualize autophagic vesiclesin vivoand follow their temporal and cellular localization in the larval heart. We observed a significant accumulation of lysosomal vesicles in the developing atrioventricular and bulboventricular regions and their respective valves. Next, we addressed the role of lysosomal degradation using a Spinster homolog 1 (spns1) mutant.spns1mutants displayed morphological and functional cardiac defects, including abnormal endocardial organization, impaired valve formation and retrograde blood flow. Single-nuclear transcriptome analysis revealed endocardial-specific differences in the expression of lysosome-related genes and alterations ofnotch1-signalling in the mutant. Endocardial-specific overexpression ofspns1andnotch1rescued features of valve formation and function. Altogether, our study reveals a cell-autonomous role of lysosomal processing during cardiac valve formation upstream ofnotch1-signalling.
Sustained bias of spatial attention in a 3T MRI scanner
Authors: Smaczny Stefan , Behle Leonie , Kuppe Sara , Karnath Hans-Otto , Lindner Axel 
Published: March 2024

AbstractThe static magnetic field of MRI scanners induces magneto-hydrodynamic stimulation of the vestibular organ (MVS) in the inner ear. This not only causes a horizontal vestibular nystagmus but also induces a horizontal bias in spatial attention. In this study, we aimed to determine the time course of MVS-induced biases in both VOR and spatial attention inside a 3T MRI-scanner as well as their respective aftereffects after participants left the scanner. Eye movements and overt spatial attention in a visual search task were assessed in healthy volunteers before, during and after a one-hour MVS period. All participants exhibited a VOR inside the scanner, which declined over time but never vanished completely. Importantly, there was also an MVS-induced horizontal bias in spatial attention and exploration, which persisted throughout the entire hour within the scanner. Upon exiting the scanner, we observed aftereffects in the opposite direction manifested in both the VOR and in spatial attention, lasting for about 6 minutes. Sustained MVS effects on spatial attention have important implications for the design and interpretation of fMRI-studies and for the development of therapeutic interventions counteracting spatial neglect.
Robust encoding of sub-sniff temporal information in the mouse olfactory bulb
Authors: Warner Tom P. A. , Tootoonian Sina , Schaefer Andreas T. 
Published: March 2024

SummaryThe sensory world is highly dynamic, and the temporal structure of stimuli contains rich information about the environment. Odour plumes are shaped by complex airflow that imprint information about the nature and spatial organisation of the olfactory environment onto their temporal dynamics. Whilst insects and mammals alike can discern high-frequency information, how temporal properties of the olfactory environment are represented in the brain remains largely unknown. Here, we presented temporally rich and systematically varying odour stimuli whilst electrically recording from the output neurons of the mouse olfactory bulb, mitral and tufted cells (MTC). We found that temporal aspects of odour stimuli could readily be read out from MTC responses, with a temporal resolution of up to 20 ms. Remarkably, temporal representation was virtually identical across three different odours. To understand which temporal features are encoded, we developed a single-cell model accurately describing both single-cell and population responses. Temporal receptive fields of MTCs translated between different odours, indicating that MTC tuning to odour quality and dynamics are partially separable. Together, this suggests a stereotypical representation of odour dynamics across projection neurons and can serve as an entry point into dissecting mechanisms underlying how information about the environment is extracted from temporally fluctuating odour plumes.
De novo antibody discovery in human blood from full-length single B cell transcriptomics and matching haplotyped-resolved germline assemblies
Authors: Beaulaurier John , Ly Lynn , Duty J. Andrew , Tyer Carly , Stevens Christian , Hung Chuan-tien , Sookdeo Akash , Drong Alex W. , Kowdle Shreyas , Turner Daniel J. , Juul Sissel , Hickey Scott , Lee Benhur 
Published: March 2024

AbstractImmunoglobulin (IGH, IGK, IGL) loci in the human genome are highly polymorphic regions that encode the building blocks of the light and heavy chain IG proteins that dimerize to form antibodies. The processes of V(D)J recombination and somatic hypermutation in B cells are responsible for creating an enormous reservoir of highly specific antibodies capable of binding a vast array of possible antigens. However, the antibody repertoire is fundamentally limited by the set of variable (V), diversity (D), and joining (J) alleles present in the germline IG loci. To better understand how the germline IG haplotypes contribute to the expressed antibody repertoire, we combined genome sequencing of the germline IG loci with single-cell transcriptome sequencing of B cells from the same donor. Sequencing and assembly of the germline IG loci captured the IGH locus in a single fully-phased contig where the maternal and paternal contributions to the germline V, D, and J repertoire can be fully resolved. The B cells were collected following a measles, mumps, and rubella (MMR) vaccination, resulting in a population of cells that were activated in response to this specific immune challenge. Single-cell, full-length transcriptome sequencing of these B cells resulted in whole transcriptome characterization of each cell, as well as highly-accurate consensus sequences for the somatically rearranged and hypermutated light and heavy chain IG transcripts. A subset of antibodies synthesized based on their consensus heavy and light chain transcript sequences demonstrated binding to measles antigens and neutralization of measles live virus.
Acute and sub-chronic toxicity of 6PPD-quinone to early-life stage lake trout (Salvelinus namaycush)
Authors: Roberts Catherine , Lin Junyi , Kohlman Evan , Jain Niteesh , Amekor Mawuli , Alcaraz Alper James , Hogan Natacha , Hecker Markus , Brinkmann Markus 
Published: March 2024

AbstractN-(1,3-Dimethylbutyl)-N’-phenyl-p-phenylenediamine-quinone (6PPD-q) is a rubber-tire derivative which leaches into surface waters from roadway runoff, from tire particles and has been identified as a possible driver of urban runoff mortality syndrome in coho salmon. Sensitivity to this toxicant is highly variable across fish species and life stages. With environmental concentrations meeting or exceeding toxicity thresholds in sensitive fishes, the potential for ecologically relevant effects is significant. There is currently no data regarding the sensitivity of lake trout (Salvelinus namaycush) to 6PPD-q. As early-life stages of fishes are typically more sensitive than adults, the goal of these studies was to evaluate the acute and sub-chronic toxicity of 6PPD-q to early-life stage lake trout. Alevins exposed from hatch until 45 days post hatch (dph) to time-weighted average 6PPD-q concentrations ranging from 0.22-13.5 μg/L exhibited a 45-day median lethal dose (LC50) of 0.39 μg/L. Deformities throughout growth were observed, with a unique pooling of blood observed in the caudal fin and eye. A subsequent acute study with exogenously feeding lake trout fry determined a 96-hr LC50of 0.50 μg/L. From these studies we can conclude that lake trout alevins and exogenously feeding fry are sensitive to 6PPD-q, which underscores the relevance of this chemical to inland freshwater ecosystems.
Faster inference of complex demographic models from large allele frequency spectra
Authors: Dilber Enes , Terhorst Jonathan 
Published: March 2024

AbstractWe presentmomi3, a new method for inferring complex demographic models using genetic variation data sampled from many populations.momi3 features many improvements over its predecessormomi2 (Kamm, Terhorst, Durbin, et al., 2020), including support for continuous migration, just-in-time compilation, and execution on GPUs; a standardized interface for specifying demographic models; and a novel importance sampling strategy that enables it to efficiently analyze data from a large number of samples. Together, these improvements lead to speedups of as much as 1000× over existing state-of-the-art methods such as ∂a∂i,moments, andmomi2. We illustrate the usefulness of our method by revisiting a model of archaic admixture using a large, recent dataset containing hundreds of human genomes from many populations.
Geographic variation in vulnerability to warming temperatures in an intertidal barnacle species
Authors: Gilman Sarah E. , Ober Gordon T. , Rognstad Rhiannon L. , Bunnenberg-Ross Madeleine , Man Tingyue 
Published: March 2024

AbstractVulnerability to warming temperatures under climate change arises when there is a gap between local climate and local physiology. Intertidal species are unique because they face two distinct thermal environments, and it is unclear which is the bigger driver of thermal physiology and vulnerability. Here we compare the thermal environments and physiology of three populations of the intertidal barnacleBalanus glandula, spanning 1460 km of its geographic range. We measured energy consumption in the laboratory across a 5-hour emersion and subsequent 6-hour immersion at 7 different emersion temperatures (10-38°C). We compared these results to one year of emersion and immersion temperature data from each location. Our results suggest that the temperatures experienced during emersion are a bigger driver of each population’s emersion thermal physiology than those experienced during immersion. We also estimated vulnerability to future warming in two ways: as the total annual energy demand and as the number of days above each population’s thermal peak. These produced conflicting results. The central population spent the most days over its thermal peak, but the northernmost population had the greatest total costs over a year. The higher energetic costs in the northernmost population may be explained in part by a strong latitudinal gradient in primary productivity that is selecting for higher energy demand in higher latitude populations. Thus, accurate predictions ofB. glandula’s response to warming temperatures will require knowledge of both future temperature and food availability.
Assessment of the efficacy of field and laboratory methods for the detection ofTropilaelaps spp
Authors: Gill Maggie C. , Chuttong Bajaree , Davies Paul , Etheridge Dan , Panyaraksa Lakkhika , Tomkies Victoria , Tonge George , Budge Giles E. 
Published: March 2024

AbstractTropilaelapsspp. are invasive mites that cause severe disease inApis melliferacolonies. The UK has deployed an elaborate surveillance system that seeks to detect these mites early in any invasion to allow the best opportunity to eradicate any incursion. Effective field and laboratory protocols, capable of reliably detecting low numbers of mites, are key to the success of any intervention. Here we compared the efficacy of established field monitoring using brood removal with an uncapping fork, and brood ‘bump’ methods with novel methods forTropilaelapsdetection modified fromVarroamonitoring schemes. In addition, we monitored the efficacy of the laboratory method for screening for mites in hive debris by floating mites in ethanol. Our results clearly indicated that novel methods such as uncapping infested brood with tweezers, catching mite drop using sticky traps and rolling adult bees in icing sugar were all significantly more likely to detectTropilaelapsthan existing methods such using an uncapping fork on infested brood, or the brood ‘bump’ method. Existing laboratory protocols that sieved hive debris and then floated the mite containing layer failed to detectTropilaelapsmites and new efficacious protocols were developed. Our results demonstrated that the national surveillance protocols forTropilaelapsmite detection required modification to improve the early detection of this damaging invasive mite.
Phosphodiesterase-5 inhibition inhibits epithelial ATP release and restores detrusor contractility in rats with type 2 diabetesviaan increase in bladder blood flow
Authors: Kabuto Takafumi , Inamura So , Kobayashi Hisato , Zha Xinmin , Nagase Keiko , Taga Minekatsu , Seki Masaya , Tanaka Nobuki , Okumura Yoshinaga , Yokoyama Osamu , Terada Naoki 
Published: March 2024

ABSTRACTPurposeThe bladder dysfunction associated with type 2 diabetes mellitus (T2DM) involves urine storage and voiding disorders. We evaluated the pathologic conditions of bladder wall in a rat model of T2DM and evaluated the effects of the phosphodiesterase-5 (PDE-5) inhibitor tadalafil (TA).Materials and MethodsMale Otsuka Long-Evans Tokushima Fatty (OLETF) rats and Long-Evans Tokushima Otsuka (LETO) rats comprised T2DM and control groups. TA was orally administered for 12 weeks. The bladder blood flow and ATP released from the bladder epithelium were measured using laser speckle imaging and an organ bath bladder distention test. The expression levels of markers of hypoxia, pro-inflammatory cytokines, and growth factors in the bladder wall were measured by real-time PCR and ELISA. The contractions of bladder strips in response to KCl and carbachol were monitored in OLETF rats.ResultsThe bladder blood flow was impaired and there was greater ATP release and vesicular nucleotide transporter (VNUT) expression in the OLETF rats than in the LETO rats, but these effects were suppressed by TA administration. Furthermore, the high expression of HIF-1α, 8-OHdG, IL-6, TNF-α, IGF-1, and bFGF in the OLETF rats was reduced by TA administration. In the OLETF rats, the contractile responses of bladder strips to KCl and carbachol were impaired, but were restored by TA administration.ConclusionsThe impairment of bladder blood flow in rats with T2DM is associated with greater ATP release and the upregulation of VNUT, markers of hypoxia, proinflammatory cytokines, and growth factors in the bladder epithelium. PDE5 inhibition has the potential to prevent the storage and voiding dysfunction associated with T2DM.
Cortisol levels, heart rate, and autonomic responses in horses during repeated road transport with different truck conditions trucks in a tropical environment
Authors: Lertratanachai Siengsaw , Poochipakorn Chanoknun , Sanigavatee Kanokpan , Huangsaksri Onjira , Wonghanchao Thita , Charoenchanikran Ponlakrit , Lawsirirat Chaipat , Chanda Metha 
Published: March 2024

AbstractHorse’s stress responses have been reported during road transport in cold but not tropical environments. Therefore, this study estimated cortisol levels, heart rate (HR), and heart rate variability (HRV) in horses during medium-distance road transport with different truck conditions in a tropical environment. Six horses were repeatedly transported in either air-conditioned trucks with full (ATF) or space (ATS) loads or non-air-conditioned trucks with full (N-ATF) and space (N-ATS) loads. Blood cortisol was determined beforehand and 5, 30, and 90 minutes post-transport. HR and HRV were assessed pre-transport and at 15-minute intervals until 90 minutes post-transport. Cortisol levels increased significantly in N-ATS horses (but non-significantly in ATF, ATS, and N-ATF horses) at 5 minutes post-transport and returned to baseline by 30 minutes post-transport. Predominant parasympathetic nervous system (PNS) activity was observed during the first few hours and returned to baseline until the destination was reached. A recurrent, increased PNS activity was detected post-transport. Interaction effects of air condition-by-loading condition-by-time, air condition-by-time, and separate effects of air condition and time were observed on HR and various HRV variables during transport. A transient increase in beat-to-beat intervals, coinciding with decreased HR, was observed in ATF horses. The PNS index increased, corresponding to a decreased sympathetic nervous system index, in ATS horses during transport. We suggest that medium-distance road transport causes no stress for transport-experienced horses in a tropical environment. Air and loading conditions impacted hormonal and autonomic modulation, causing different responses in horses transported in differently conditioned trucks.
CD4+Trm sustain the chronic phase of auto-immune neuroinflammatory disease
Authors: Pignata Aurora , Frieser David , Hsiao Cheng-Chih , Engelenburg Hendrik J. , Alis Marine , Gonzalez-Fierro Carmen , Cazaentre Vincent , Miranda-Capet Romain , Dufourd Eloise , Vermeulen Thais , Aida Amel , Gisbergen Klaas Van , Blanchard Nicolas , Hamann Jörg , Smolders Joost , Liblau Roland S. , Masson Frederick 
Published: March 2024

AbstractTherapeutic options against multiple sclerosis (MS) preventing T cell migration to the central nervous system (CNS) have remarkable clinical effects against the relapsing-remitting (RRMS) form of the disease, while they are poorly effective against its progressive form (PMS). Disability progression in PMS is thought to result from an interplay between smoldering local inflammation and neurodegeneration. We postulated that an ongoing inflammatory process mediated by CNS-resident memory CD4+T cells (CD4+Trm) could contribute to promote disease chronicity independently ofde novorecruitment of peripheral autoreactive T cells. Indeed, our results revealed the presence ofbona fideCD4+Trm expressing CD69, CXCR6, P2RX7, CD49a and the transcription factor Hobit in the CNS of mice with chronic experimental autoimmune encephalomyelitis (EAE) and in the brain of persons with PMS. Single-cell transcriptional analysis uncovered their transcriptional heterogeneity and inflammatory potential and, accordingly, CD4+Trm preferentially localized within inflammatory lesions. Finally, depletion of both the recirculating and the CNS-resident CD4+T cell compartments was required to alleviate neurological signs during the chronic phase of EAE. Our results, therefore, indicate that CD4+Trm actively contribute to maintain a chronic inflammatory state in the CNS, promoting damage and/or preventing repair, and suggest that new therapeutic strategies for the treatment of PMS should consider targeting the CNS-resident T cell compartment.
Fast exploration is coupled with a less choosy but more reactive learning style in a generalist predator
Authors: Kuo Chi-Yun , Chen Yu-Hsi , Meng Ai-Ching , Wu Yu-Zhe , Yang Shan-Yu , Yeh Ching-Ning 
Published: March 2024

AbstractThe hypothesis of slow-fast syndromes predicts a correspondence between personality type and learning style; fast explorers would have a more proactive (fast but inflexible) learning style and slow explorers would be more reactive (slow but flexible) learners. Empirical evidence for this personality-cognition coupling remains inconclusive and heavily biased towards birds. Moreover, most studies did not examine the personality-cognition correlation when the cognitive task is discerning food quality, a scenario directly related to energy acquisition that underpins the evolution of slow-fast syndromes. In this study, we examined the exploration-cognition correlation in the context of avoidance learning in an opportunistic predator - the common sun skinkEutropis multifasciata. We quantified exploration tendencies of individuals in an unfamiliar environment and compared foraging behaviours when lizards associated prey colour and quality during the initial learning trials and subsequent reverse learning trials, where the prey colour-taste combinations were switched. We found that fast explorers were less choosy but more reactive foragers, whereas slow explorers exhibited the opposite learning style. Interestingly, there was no evidence for a learning speed-flexibility trade-off. Our findings are in contrast with conventional predictions and suggest that the two types of exploration-cognition coupling could be different viable responses to fast-changing environmental predictability.
Challenges in quantifying functional redundancy and selection in microbial communities
Authors: Ho Po-Yi , Huang Kerwyn Casey 
Published: March 2024

ABSTRACTMicrobiomes can exhibit large variations in species abundances but high reproducibility in abundances of functional units, an observation often considered evidence for functional redundancy. Based on such reduction in functional variability, selection is hypothesized to act on functional units in these ecosystems. However, the link between functional redundancy and selection remains unclear. Here, we show that reduction in functional variability does not always imply selection on functional profiles. We propose empirical null models to account for the confounding effects of statistical averaging and bias toward environment-independent beneficial functions. We apply our models to existing data sets, and find that the abundances of metabolic groups within microbial communities from bromeliad foliage do not exhibit any evidence of the previously hypothesized functional selection. By contrast, communities of soil bacteria or human gut commensals grownin vitroare selected for metabolic capabilities. By separating the effects of averaging and functional bias on functional variability, we find that the appearance of functional selection in gut microbiome samples from the Human Microbiome Project is artifactual, and that there is no evidence of selection for any molecular function represented by KEGG orthology. These concepts articulate a basic framework for quantifying functional redundancy and selection, advancing our understanding of the mapping between microbiome taxonomy and function.
hoodscanR: profiling single-cell neighborhoods in spatial transcriptomics data
Authors: Liu Ning , Martin Jarryd , Bhuva Dharmesh D , Chen Jinjin , Li Mengbo , Lee Samuel C. , Kharbanda Malvika , Cheng Jinming , Mohamed Ahmed , Kulasinghe Arutha , Chen Yunshun , Tan Chin Wee , Davis Melissa J 
Published: March 2024

AbstractUnderstanding complex cellular niches and neighborhoods are giving us new insights into tissue biology. Accurate neighborhood identification is crucial, yet existing methodologies often struggle to detect mixed neighborhoods and generate cell-specific neighborhood profiles. To address these limitations, we introduce hoodscanR, a Bioconductor package designed for neighborhood identification and downstream analyses using spatial data. Applying hoodscanR to breast and lung cancer datasets, we showcase its efficacy in conducting detailed neighborhood analyses and identify subtle transcriptional changes in tumor cells from different neighborhoods. Such analyses can help researchers gain valuable insights into disease mechanisms and potential therapeutic targets.