bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic benchmarking of mass spectrometry-based antibody sequencing reveals methodological biases
Authors: Chernigovskaya Maria , Lê Quý Khang , Stensland Maria , Singh Sachin , Nelson Rowan , Yilmaz Melih , Kalogeropoulos Konstantinos , Sinitcyn Pavel , Patel Anand , Castellana Natalie , Bonissone Stefano , Foss Stian , Andersen Jan Terje , Sandve Geir Kjetil , Jenkins Timothy Patrick , Noble William S. , Nyman Tuula A. , Snapkow Igor , Greiff Victor 
Published: November 2024

AbstractThe circulating antibody repertoire is crucial for immune protection, holding significant immunological and biotechnological value. While bottom-up mass spectrometry (MS) is the most widely used proteomics technique for profiling the sequence diversity of circulating antibodies (Ab-seq), it has not been thoroughly benchmarked. We quantified the replicability and robustness of Ab-seq using six monoclonal antibodies with known protein sequences in 70 different combinations of concentration and oligoclonality, both with and without polyclonal serum IgG background. Each combination underwent four protease treatments and was analyzed across four experimental and three technical replicates, totaling 3,360 LC-MS/MS runs. We quantified the dependence of MS-based Ab-seq identification on antibody sequence, concentration, protease, background signal diversity, and bioinformatics setups. Integrating the data from experimental replicates, proteases, and bioinformatics tools enhanced antibody identification.De novopeptide sequencing showed similar performance to database-dependent methods for higher antibody concentrations, butde novoantibody reconstruction remains challenging. Our work provides a foundational resource for the field of MS-based antibody profiling.
Connectivity and population structure in a marginal sea – a review
Authors: Henriksson Simon , Jorde Per Erik , Berkström Charlotte , Søvik Guldborg , De Wit Pierre , Knutsen Halvor , Moland Even , André Carl , Jahnke Marlene 
Published: November 2024

AbstractThe current biodiversity crisis calls for conservation measures that limit the negative human impact on important habitats and sensitive wild populations. To effectively protect biodiversity at all levels, including intraspecific diversity, conservation measures should be aligned with the connectivity and genetic structure of wild populations. In this review, we synthesise scientific literature on the connectivity and population structure of marine species in the Skagerrak – a marginal sea in the northeast Atlantic Ocean. We discuss the results in relation to the current management practices in the region, as well as the general transferability of our findings. The Skagerrak is one of the most intensively studied regions within this research field, and our findings show that the overall connectivity with adjacent seas is high, but asymmetric, for most species. Simultaneously, most species have populations in the Skagerrak distinct from both each other, and those in adjacent seas.Most of this population structure is associated with the convoluted Skagerrak coastline – population structure is common both among coastal populations and between coastal and offshore populations. In many mobile species, multiple populations are temporally sympatric in certain areas, but retain their genetic divergence through natal homing or other barriers to gene flow. The presence of population structure despite high connectivity is a challenge for area-based protection measures, and calls for temporally flexible management that also monitors intraspecific genetic diversity on multiple timescales.
Detection of Unlabeled Micro- and Nanoplastics in Unstained Tissue with Optical Photothermal Infrared Spectroscopy
Authors: Duswald Kristina , Pichler Verena , Kopatz Verena , Limberger Tanja , Karl Verena , Wimberger David , Zimmerleiter Robert , Wadsak Wolfgang , Hettich Mike , Kenner Lukas , Brandstetter Markus 
Published: November 2024

ABSTRACTIn this study, we investigate the efficacy of Optical Photothermal Infrared (O-PTIR) spectroscopy, also known as mid-infrared photothermal (MIP) microscopy, for the detection of micro- and nano plastics (MNPs) down to diameters of 250 nm in mammalian tissues. Experiments with bothin vitro3D cell cultures derived from HTC116 colorectal cancer cell line andin vivomouse tissue models were conducted to evaluate the spatial resolution limits and quality of spectra that formed the basis for label-free and non- destructive identification of MNPs. Our findings demonstrate the superior resolution of O-PTIR in imaging individual particles of 250 nm in mouse kidney tissues, surpassing the capabilities of traditional FTIR spectroscopy, which was applied as a reference technique. Furthermore, we introduce a semi-automated image analysis that incorporates machine learning algorithms to accelerate the detection process, thus improving throughput and minimizing the potential for human error. The results confirm that O-PTIR produces high-quality, artefact-free spectral images in a contact-less manner and significantly outperforms FTIR in terms of spatial resolution and signal-to-noise ratio in complex biological matrices.
QT-WEAVER: Correcting quartet distribution improves phylogenomic analyses despite gene tree estimation error
Authors: Bin Hasan Navid , Sohaib  , Bayzid Md. Shamsuzzoha 
Published: November 2024

AbstractSummarizing individual gene trees into species phylogenies using coalescent-based methods has become a standard approach in phylogenomics. However, gene tree estimation error (GTEE) arising from a combination of reasons (ranging from analytical factors to more biological causes, as in short gene sequences) can potentially impact the accuracy of phylogenomic inference. We, for the first time, introduce the problem of correcting the quartet distribution induced by a set of estimated gene trees, which involves updating the weights of the quartets to better reflect their relative importance within the gene tree distribution. We present QT-WEAVER, the first method of its kind, which learns the conflicts within the quartet distribution induced by a given set of gene trees and generates an updated quartet distribution by adjusting the weights accordingly. QT-WEAVER is a general- purpose technique needing no explicit modeling of the subject system or reasons for GTEE or gene tree heterogeneity. Experimental studies on a collection of simulated and empirical data sets suggest that QT-WEAVER can effectively account for GTEE, which results in a substantial improvement in the species tree accuracy. Additionally, the concept of quartet conflicts and related algorithmic and combinatorial innovations introduced in this study will benefit various quartet-based computations. Therefore, QT-WEAVER advances the state-of-the-art in species tree estimation from gene trees in the face of GTEE. QT-WEAVER is freely available in open-source form athttps://github.com/navidh86/QT-WEAVER.
The Interaction Of Diet-Induced Obesity And Chronic Stress In A Mouse Model Of Menopause
Authors: Knox Nadja , Yasrebi Ali , Caramico Daniel , Wiersielis Kimberly , Samuels Benjamin A. , Roepke Troy A. 
Published: November 2024

ABSTRACTMenopause is characterized by the cessation of ovarian hormone production. During postmenopause, cisgender women face increased risks of obesity, cognitive decline, and mood disorder. Mood disorders are associated with exposure to chronic stress. We investigated the combined effects of a high-fat diet (HFD) and chronic stress exposure in a mouse model of menopause using 4-vinylcyclohexene diepoxide (VCD), a selective ovotoxicant that gradually depletes ovarian follicles and hormones. Starting at 6 months, 82 female WT C57BL/6J mice received saline or VCD (130 mg/kg i.p.) 5 days per week for 3 weeks. One month after injection, mice were fed either low-fat diet (LFD) or HFD for 8 weeks followed by 6 weeks of chronic variable mild stress (CVMS). Post-CVMS, mice were either processed for gene expression of the anterodorsal BNST or behavior tests to assess cognitive and anxiety-related behaviors. Plasma samples were collected to analyze metabolic hormones and corticosterone levels. VCD-treated HFD-fed mice had higher fat and body mass, and elevated fasting glucose levels compared to controls and more pronounced avoidance behaviors and cognitive impairments. LFD-fed, VCD-treated mice exhibited less exploration of novel objects and open spaces compared to OIL and HFD counterparts. VCD elevated corticosterone levels on LFD and increased BNSTPacapgene expression on HFD. These findings highlight cognitive repercussions of estrogen deficiency and suggest a potential protective effect of a HFD against some of the adverse outcomes associated with menopause. Our study emphasizes the importance of considering dietary and hormonal interactions in the development of therapeutic strategies.
The transcription factor GABPA is a master regulator of naïve pluripotency
Authors: Zhou Chengjie , Wang Meng , Zhang Chunxia , Zhang Yi 
Published: November 2024

AbstractThe establishment of naïve pluripotency is a continuous process starting with the generation of inner cell mass (ICM) which then differentiating into epiblast (EPI). Recent studies have revealed key transcription factors (TFs) for ICM formation, but which TFs initiate EPI specification remains unknown. Here, using a targeted rapid protein degradation system, we show that GABPA is not only a regulator of major ZGA, but also a master EPI specifier required for naïve pluripotency establishment by regulating 47% of EPI genes during E3.5 to E4.5 transition. Chromatin binding dynamics analysis suggests that GABPA controls EPI formation at least partly by binding to the ICM gene promoters occupied by the pluripotency regulators TFAP2C and SOX2 at E3.5 to establish naïve pluripotency at E4.5. Our study not only uncovers GABPA as a master pluripotency regulator, but also supports the notion that mammalian pluripotency establishment requires a dynamic and stepwise multi-TFs regulatory network.
ConvexGating infers gating strategies from clusters in single cell cytometry data
Authors: Friedrich Vincent D. , Mai Karola , Hofer Thomas P. , Nößner Elfriede , Bonaguro Lorenzo , Hartmann Celia L. , Frolov Aleksej , Carraro Caterina , Hamada Doaa , Hadaddzadeh-Shakiba Mehrnoush , Scholz Markus , Theis Fabian J. , Beyer Marc D. , Schultze Joachim L. , Büttner Maren 
Published: November 2024

AbstractManual expert gating remains common practice for the definition of specific cell populations in the analysis of flow cytometry data. The increasing number of measured parameters per individual cell and high inter-rater variability makes manual gating inconsistent in many scenarios such as multi-center studies. Here, we propose ConvexGating, an AI tool that automatically learns gating strategies in an unbiased, fully data-driven, yet interpretable manner. ConvexGating scales efficiently with increasing parameter space, creating proficient strategies with low-contamination in the extracted population for previously known and so far unknown or ill-defined cell populations. The inferred strategies are independent of parent populations, for instance, plasmacytoid dendritic cells (pDCs) can be fully identified as CD45RA- CD123+. In addition to flow cytometry data, ConvexGating derives gating strategies for cyTOF (Cytometry by Time of Flight) and CITEseq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) data and supports optimal design of marker panels for cell sorting.
Prefrontal cortex encodes behavior states decoupled from movement
Authors: Rautio Ida Välikangas , Nevjen Fredrik , Hem Ingeborg , Dunn Benjamin A. , Whitlock Jonathan R. 
Published: November 2024

AbstractPrefrontal cortex is often viewed as an extension of the motor system, but little is understood of how it relates to natural motor behavior. We therefore tracked the kinematics of freely moving rats performing minimally structured tasks and measured which aspects of behavior were read out in prefrontal neural populations. Naturalistic behaviors such as rearing or chasing a bait were each encoded by unique neural ensembles, but the behavioral representations were not anchored to posture or movement. Rather, the coding of kinematic features depended on their relevance to the animals’ current behavior or which task the animal performed. Behavior-specific ensembles often preceded and outlasted physical actions and, accordingly, prefrontal population activity evolved at slower timescales than in motor cortex. These findings argue that prefrontal coding of behavior is not locked to motor output, and may instead reflect motivations to perform certain actions rather than the actions themselves.HighlightsPrefrontal neural ensembles uniquely encode different naturalistic actionsBehavioral tuning is not explained by movement kinematicsPopulation activity in prefrontal cortex evolves slower than in M1Single-cell coding of behavior varies across tasks yet ensemble coding is stable
CETP expression in females increases body metabolism under both cold exposure and thermoneutrality contributing to a leaner phenotype
Authors: Castelli Júlia Z. , Raposo Helena F. , Navarro Claudia D. C. , Lazaro Carolina M. , Sartori Marina R. , Costa Ana Paula Dalla , Nogueira Pedro A. S. , Velloso Lício A. , Vercesi Anibal E. , Oliveira Helena C. F. 
Published: November 2024

ABSTRACTSusceptibility to obesity differs depending on the genetic background and housing temperatures. We have recently reported that CETP expressing female mice are leaner due to increased lipolysis, brown adipose tissue (BAT) activity and body energy expenditure compared to non-transgenic (NTg) littermates under standard housing temperature (22°C). The aim of this study is to evaluate how CETP expression affect body temperature, composition and metabolism during cold exposure (4°C) and thermoneutrality (30°C). When submitted to cold, CETP mice maintained rectal temperature, body weight and food intake similarly to NTg mice along acute or chronic exposure to 4ºC. The body oxygen consumption in response to an isoproterenol challenge was 21% higher at 22ºC, and 41% higher after 7 days of cold exposure in CETP than in NTg mice. In addition, BAT biopsies from CETP mice showed reduced lipid content and increased basal oxygen consumption rates. Under thermoneutrality (30ºC), when BAT activity is inhibited, CETP mice showed higher rectal and tail temperatures, increased food intake and increased energy expenditure. Lean mass was elevated and fat mass reduced in CETP mice kept at 30ºC. In this thermoneutrality condition, soleus muscle, but not gastrocnemius or liver of CETP mice showed increased mitochondrial respiration rates. These data indicate that CETP expression confers a greater capacity of elevating body metabolic rates at both cold exposure, through BAT activity, and at thermoneutrality, through increased muscle metabolism. Thus, the CETP expression levels in females should be considered as a new influence in the contexts of obesity and metabolic disorders propensity.NEW & NOTEWORTHYWe demonstrate here that CETP expression in females increases body metabolism under cold (4ºC) and thermoneutrality (30ºC). Since this has also been shown at 22ºC, it seems a constitutive feature of CETP expression. Brown adipose tissue and red fiber muscle contribute to the overall high metabolism and leaner phenotype of CETP mice. Elevated mitochondrial respiration rates were demonstrated in these tissues. Thus, CETP is a new relevant variable in the context of obesity and metabolic disorders.GRAPHICAL ABSTRACT
Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism
Authors: Diaz Escarcega Rocio , M. J. Vijay Kumar , Kyriakopoulos Vasilia E. , Ortiz Guadalupe J. , Gusdon Aaron M. , Fan Huihui , Peesh Pedram , Blasco Conesa Maria P. , Colpo Gabriela Delevati , Ahnstedt Hilda W. , Couture Lucy , Kim Stella H. , Hinojosa Miriam , Farrell Christine M. , Marrelli Sean P. , Urayama Akihiko , Ganesh Bhanu P. , Schulz Paul E. , McCullough Louise D. , Tsvetkov Andrey S. 
Published: November 2024

ABSTRACTAlzheimer’s disease (AD) affects more women than men. Although women live longer than men, it is not longevity alone, but other factors, including metabolic changes, that contribute to the higher risk of AD in women. Metabolic pathways have been implicated in AD progression, but studies to date examined targeted pathways, leaving many metabolites unmeasured. Sex is often a neglected biological variable, and most metabolomic studies were not designed to investigate sex differences in metabolomic profiles. Here, we performed untargeted metabolomic profiling of sera from male and female patients with mild cognitive impairment (MCI), a common precursor to AD, and matched controls. We discovered significant metabolic changes in individuals with MCI, and found several pathways that were strongly associated with sex. Peptide energy metabolism demonstrated sexual dimorphism. Lipid pathways exhibited the strongest differences between female and male MCI patients, including specific phosphatidylcholine lipids, lysophospholipids, long-chain fatty acids, and monoacylglycerols. 1-palmitoleoyl glycerol and 1-arachidonoyl glycerol were higher in female MCI subjects than in male MCI subjects with no differences between control males and females. Conversely, specific dicarboxylic fatty acids were lower in female MCI subjects than male MCI subjects. In cultured astrocytes, 1-arachidonoyl glycerol promoted phosphorylation of the transcriptional regulator sphingosine kinase 2, which was inhibited by the transient receptor potential vanilloid 1 receptor antagonists, as well as chromatin remodelling. Overall, we identified novel sex-specific metabolites in MCI patients that could serve as biomarkers of MCI in both sexes, help further define AD etiology, and reveal new potential prevention strategies for AD.Highlights▪Individuals with MCI experience significant metabolic changes.▪Lipid pathways demonstrated the strongest sexual dimorphism in MCI.▪1-monoacylglycerols showed a robust sex association, being higher in MCI females.▪Sex-specific metabolites may be MCI biomarkers in each sex.
Proof-of-Concept Validation of Noninvasive Detection of Cortical Spreading Depolarization with High Resolution Direct Current-Electroencephalography
Authors: Brown Benjamin R. , Hund Samuel J. , Easley Kirk A. , Singer Eric L. , Shuttleworth C. William , Carlson Andrew P. , Jones Stephen C. 
Published: November 2024

AbstractBackground/ObjectiveCortical spreading depolarization (SD) is increasingly recognized as a major contributor to secondary brain injury. Noninvasive SD monitoring would enable the institution of SD-based therapeutics. Our primary objective is to establish proof-of-concept validation that scalp DC-potentials can provide noninvasive SD detection by comparing scalp direct-current (DC)-shifts from a high-density electrode array to SDs detected by gold-standard electrocorticography (ECoG). Our secondary objective is to assess usability and artifact tolerance.MethodsAn 83×58 mm thermoplastic elastomer array with 29 6-mm diameter Ag/AgCl 1-cm spaced electrodes, the CerebroPatch™ Proof-of-Concept Prototype, was adhesively placed on the forehead with an intervening electrode gel interface to record DC-electroencephalography in normal volunteers and severe acute brain injury patients in the neuro-intensive care unit some with and some without invasive ECoG electrodes. The scalp and ECoG voltages were collected by a Moberg® Advanced ICU Amplifier. Artifacts were visually identified and usability issues were recorded. SD was scored on ECoG based on DC-shifts with associated high-frequency suppression and propagation. A six-parameter Gaussian plus quadratic baseline model was used to estimate ECoG and scalp electrode time-courses and scalp-voltage heat-map movies. The similarity of the noninvasive scalp and invasive ECoG DC-shift time-courses was compared via the Gaussian fit parameters and confirmed if the Coefficient-of-Determination was >0.80.ResultsUsability and artifact issues obscured most scalp Prototype device data of the 140 ECoG-coded SDs during 11 days in one sub-arachnoid hemorrhage patient. Twenty-six of these DC-shifts were in readable, artifact-free portions of scalp recordings and 24 of these had a >0.80 Coefficient-of-Determination (0.98[0.02], median[IQR]) between invasive ECoG and noninvasive Prototype device DC-shifts. Reconstructed heat-map movies of the scalp DC-potentials showed a 5-cm extent, -460 µV peak region that persisted for ∼70 sec. These data suggest that these scalp DC-shifts (peak -457±69 µV [mean±StD], full-width-half maximum 70.9±5.92 sec, area 18.7±2.76 cm2) depicted in the heat-map movies represent noninvasively detected SDs.ConclusionsThese results using 26 SDs as the observational units suggest that noninvasive SD detection is possible using scalp DC-potential signals with a high spatial resolution EEG array. Although the high artifact burden data and low usability records were limiting, negative results, they serve as an important entrepreneurial recipe for a future, re-designed device that would reduce artifacts and improve usability for DC-EEG SD detection needed to enable multi-modal monitoring for secondary brain injury.
The impact of research results feedback on the lived experiences of elderly participants in the DIMAMO health demographic site: a case of AWI-Gen Participants
Authors: Mashaba Reneilwe G. , Ntimana Cairo B. , Makoti Precious , Mothapo Katlego , Tlouyamma Joseph , Seakamela Kagiso P. 
Published: November 2024

AbstractBackgroundsThe concept of engaging the community on the results if research or returning individual result to the respective participants seems more of an afterthought than an integral part of research processes. Therefore, the current study aims to assess the impact of research results feedback among study participants from a rural black community of low socio-economic status.MethodsThe study was qualitative. The consolidated criteria for reporting qualitative research (COREQ) guiding principle was used to present study findings. Data was collected through qualitative face-to-face in-depth interviews using an interview guide, between September and October 2024 in the Dikgale area, Limpopo province, South Africa. The transcripts were anonymized before entering them into QSR NVivo 10 (QSR International, Warrington, UK) to aid in analysis. The interview data was analyzed using a deductive content analysis method to develop themes.ResultsThe present study included about 31 individuals of which 79% were women and 29% were men. Most participants in the present study had high school qualification as their highest level of education (74.20%) followed by those with no formal education and primary school level education at 16.15% and 12.90% respectively. Themes, identified through deductive analysis include health and lifestyle awareness, perceived benefits of research participation, community perception of health research, economic and social motivations, and challenges and concerns.ConclusionThe present study shed light on the importance of retaining individual results for participants in health research. The themes that were generated showed that participants altered their lives and health-seeking behavior because of the information they got from participating in research a situation that would not have happened if they did not have the results back.