bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biocompatibility of KAPs-Depleted Residual Hair
Authors: Meer Allison , Mathews Aidan , Cabral Mariana , Tarabokija Andrew , Carroll Evan , Chaudhry Henna , Paszek Michelle , Radecker Nancy , Palaia Thomas , de Guzman Roche C. 
Published: May 2024

ABSTRACTThis work is an in-depth investigation of thein vitroandin vivobiocompatibility of processed and treated residual human hair samples with intact cuticle layers. The specimens included oxidized hair with no melanin (BLH) and hair with medium-(M-KAP) and low-(L-KAP) levels of keratin associated proteins (KAPs), confirmed through gel electrophoresis, electron microscopy, and trichrome histological staining, in comparison to the untreated regular hair (REG) control. All hair groups, high KAPs (H-KAPs: REG and BLH), M-KAP, and L-KAP, were found to be non-cytotoxic in the adipose fibroblast cell line’s response to their extracts based on the ISO 10993-5 medical device biomaterial testing standard.In vivomouse subcutaneous implantation (ISO 10993-6, local effects) at 2 weeks showed that the samples caused a foreign body response (FBR) with a thin fibrous encapsulation at a mean value of 28% relative skin dermis thickness; but notably, the L-KAP implant mitigated a statistically significant decrease in FBR area compared to H-KAP’s (REG and/or BLH) and a lower number of cells, including immune cells of mostly macrophages and mast cells on the biomaterial’s surface, normalized to implant and tissue coverage. In the bulk of the capsules, blood vessels and collagen extracellular matrix densities were similar among groups. These findings suggest that small globular KAPs diffuse out of the cortex to the host-biomaterial interface which induce a slightly elevated FBR but limited to the implant’s surface vicinity. On-going follow-up research focuses on purer keratin-based macromolecularly organized residual hair biomaterials, those with depleted KAPs, for drug-delivery gel implants as they are deemed the most biocompatible.Statement of SignificanceHuman hair is an abundant biological product that is regularly discarded and wasted but has the potential to be a clinical implantable allograft biomaterial. There are currently just two FDA class II-510(k)-approved medical devices from hair, limited to surface / skin wound care use, and no class III-PMA or biologics-BLA implants. Also, these products and those in research and development phases are based on soluble keratin and KAPs extracts utilizing tedious processing conditions and requiring oxidation reaction for reassembly into gels and scaffolds. Here we describe that the insoluble residual hair biomaterials with organized keratin structure, higher-degree of disulfide crosslinks, and particularly those with depleted KAPs have increased biocompatibility based on pre-clinical ISO 10993 standards. This novel natural biomaterials are now being developed as drug-delivery implantable gels for clinical applications.
Neuronal downregulation ofPLCG2impairs synaptic function and elicits Alzheimer disease hallmarks
Authors: Coulon Audrey , Rabiller Florian , Takalo Mari , Roy Avishek , Martiskainen Henna , Siedlecki-Wullich Dolores , Mendes Tiago , Lemeu Celia , Carvalho Lukas-Iohan , Ehrardt Anaël , Melo de Farias Ana Raquel , Hulsman Marc , Najdek Chloé , Lannette-Weimann Nina , Freire-Regatillo Alejandra , Amouyel Philippe , Charbonnier Camille , Dols-Icardo Orio , Jeskanen Heli , Willman Roosa-Maria , Kuulasmaa Teemu , Kurki Mitja , Hardy John , Wagner Richard , Heikkinen Sami , Holstege Henne , Mäkinen Petra , Nicolas Gaël , Mead Simon , Wagner Michael , Ramirez Alfredo , Rauramaa Tuomas , Palotie Aarno , Sims Rebecca , Soininen Hilkka , van Swieten John , Williams Julie , Bellenguez Céline , Grenier-Boley Benjamin , Gelle Carla , Lambert Erwan , Ayral Anne-Marie , Demiautte Florie , Costa Marcos R. , Deforges Séverine , Kilinc Devrim , Mulle Christophe , Chapuis Julien , Hiltunen Mikko , Dumont Julie , Lambert Jean-Charles 
Published: May 2024

ABSTRACTWe developed a high content screening to investigate how Alzheimer disease (AD) genetic risk factors may impair synaptic mechanisms in rat primary neuronal cultures. Out of the gene targets identified, we found that shRNA-mediated downregulation ofPlcg2in mouse dentate gyrus neurons consistently impaired dendritic morphology and synaptic function. In human neuronal cultures (hNCs),PLCG2downregulation also impaired synaptic function and was associated with increased levels of Aβ and Tau phosphorylation, potentiallyviathe AKT/GSK3β axis. Very rarePLCG2loss-of-function (LoF) variants were associated with a 10-fold increased AD risk.PLCG2LoF carriers exhibit low mRNA/proteinPLCG2/PLCγ2 levels, consistent with nonsense-mediated mRNA decay mechanisms. Restoring PLCγ2 levels in shPLCG2-hNCs fully reversed the disease-related phenotypes. Our findings indicate that the downregulation of PLCγ2 increases the risk of AD by impairing synaptic function and increasing the levels of Aβ and Tau phosphorylation in neurons.
A first insight into the developability of an IgG3: A combined computational and experimental approach
Authors: Armstrong Georgina B. , Lewis Alan , Shah Vidhi , Taylor Paul , Jamieson Craig J. , Burley Glenn A. , Lewis Will , Rattray Zahra 
Published: May 2024

ABSTRACTImmunoglobulin G 3 (IgG3) monoclonal antibodies (mAbs) are high value scaffolds for developing novel therapies. Despite their wide-ranging therapeutic potential, IgG3 physicochemical properties and developability characteristics remain largely under-characterised. Protein-protein interactions elevate solution viscosity in high-concentration formulations impacting physico-chemical stability, manufacturability, and injectability of mAbs. Therefore, in this manuscript, the key molecular descriptors and biophysical properties of a model anti-IL-8 IgG1 and its IgG3 ortholog are characterised. A computational and experimental framework was applied to measure molecular descriptors impacting on their downstream developability. Findings from this approach underpin a detailed understanding of the molecular characteristics of IgG3 mAbs as potential therapeutic entities. This work is the first report examining the manufacturability of IgG3 for high concentration mAb formulations. While poorer conformational and colloidal stability, and elevated solution viscosity was observed for IgG3, future efforts controlling surface potential through sequence-engineering of solvent-accessible patches can be used to improve biophysical parameters that dictate mAb developability.
Magnesium hydroxide nanoneedles derived fromAnthocleista schweinfurthiiGilg (Loganiaceae) support mesenchymal stromal cell proliferation and wound healing
Authors: Eya’ane Meva Francois , Pereira Rita , Ngnihamye Sandrine Elodie , Armel Florian Tchangou Njiemou , Ntoumba Agnes Antoinette , Hzounda Fokou jean Batiste , Beglau Thi Hai Yen , Fetzer Marcus N. A. , Kaul Marilyn , Schlierf Bianca , Mintang Fongang Ulrich Armel , Belle Ebanda Kedi Phillipe , Fannang Simone Veronique , Herrmann Marietta , Janiak Christoph 
Published: May 2024

AbstractMultiple metallic nanoparticles are able to promote cellular and tissue health, but these nanoparticles can be difficult to synthesize and can also cause unintended side-effects. Here, we study the effects on wounds healing and bone reparation of Mg(OH)2fromAnthocleista schweinfurthiiGilg (Loganiaceae) leaves (AS), which are local to the Africa region and have been used in traditional medicine to treat injuries. Mg(OH)2nanoneedles were synthesized from aqueous extracts ofAnthocleista schweinfurthiiGilg (Loganiaceae) leaves (AS) and magnesium nitrate. The quick polydispersing and crystallized Mg(OH)2-metal interface was found to be covered in plant secondary metabolites. We call this compound Mg(OH)2-AS. Using an acute dermal toxicity experiment on animal model, we determined that Mg(OH)2-AS is safe for topical application.In vitroexperiments suggest that Mg(OH)2-AS has anti-inflammatory potential, andin vivowound healing assays in Wistar rats indicate that Mg(OH)2-AS can enhance wound healing. To investigate Mg(OH)2-AS effects on the cellular level, we used bone marrow mesenchymal stromal cells (BM-MSCs). In contrast to pure Mg(OH)2or AS, cell viability and proliferation were not impaired by Mg(OH)2-AS. Cell morphology remained unchanged upon media supplementation with Mg(OH)2-AS. Preliminary results further indicate enhanced osteogenic differentiation of BM-MSCs in media supplied with ascorbic acid, β-glycerophosphate and dexamethasone and addition of Mg(OH)2-AS. These findings motivate further research towards the inclusion of the material in implants for bone fracture healing.
Nanomotif: Leveraging DNA Methylation Motifs for Genome Recovery and Host Association of Plasmids in Metagenomes from Complex Microbial Communities
Authors: Heidelbach Søren , Dall Sebastian Mølvang , Bøjer Jeppe Støtt , Nissen Jacob , van der Maas Lucas N.L. , Sereika Mantas , Kirkegaard Rasmus H. , Jensen Sheila I. , Kousgaard Sabrina Just , Thorlacius-Ussing Ole , Hose Katja , Nielsen Thomas Dyhre , Albertsen Mads 
Published: May 2024

AbstractDNA methylation is found across all domains of life but is a rarely used feature in recovery of metagenome-assembled genomes (MAGs). Recently, Oxford Nanopore introduced all context methylation detection models. We leveraged this to develop Nanomotif, which identifies and exploits methylation motifs for enhanced MAG recovery. We demonstrate how Nanomotif enables database-independent contamination removal from high-quality MAGs and host association of plasmids directly from Nanopore sequencing data in complex metagenomes.
Bilateral field advantage of spatial attention in macaque lateral prefrontal cortex
Authors: Kadijani Maryam Nouri , Backen Theda , Machanda Kaustubh , Mody Sandeep K , Treue Stefan , Martinez-Trujillo Julio C. 
Published: May 2024

ABSTRACTAllocating visual attention to behaviorally relevant stimuli is easier when distractors are located in the opposite visual hemifield relative to when they are in the same hemifield. The neural mechanisms underlying this bilateral field advantage remains unclear. We documented this effect in two macaques performing a covert spatial attention task in two different conditions: when the target and distracter were positioned in different hemifields (across condition), and when they were positioned on the top and bottom quadrants within the same visual hemifield (within condition). The animals’ behavioral performance at detecting a change in the attended stimulus was higher in the across relative to the within condition. We recorded the responses of lateral prefrontal cortex (LPFC, area 8A) neurons in one animal. The proportion of LPFC neurons encoding the allocation of attention was larger in the across relative to the within condition. The latter was accompanied by an increase in the ability of single neurons to discriminate the allocation of attention in the across relative to the within condition. Finally, we used linear classifiers to decode the allocation of attention from the activity of neuronal ensembles and found a similar bilateral field advantage in decoding performance in the across relative to the within condition. Our finding provides a neural correlate of the bilateral field advantage reported in behavioral studies of attention and suggest that the effect may originate within the LPFC circuitry.
The mechanisms and neural signature of average numerosity perception
Authors: Togoli Irene , Collignon Olivier , Bueti Domenica , Fornaciai Michele 
Published: May 2024

ABSTRACTThe human brain is endowed with an intuitive sense of number allowing to perceive the approximate quantity of items in a scene, or “numerosity.” This ability is not limited to items distributed in space, but also to events unfolding in time and to theaveragenumerosity of dynamic scenes. How the brain computes and represents the average numerosity over time however remains mostly unclear. Here we investigate the mechanisms and electrophysiological (EEG) signature of average numerosity perception. To do so, we used dynamic stimuli composed of 3-12 arrays presented for 50 ms each, and asked participants to judge the average numerosity of the sequence. Our results first show that the weight of different arrays in the sequence in determining the judgement is subject to both primacy and recency effects, depending on the length of the sequence. Moreover, we show systematic perceptual adaptation effects across trials, with the bias on numerical estimates depending on both the average numerosity and length of the preceding stimulus. The EEG results show numerosity-sensitive brain responses starting very early after stimulus onset, and that activity around the offset of the sequence can predict both the accuracy and precision of judgments. Additionally, we show a neural signature of the adaptation effect at around 300 ms, whereby the amplitude of brain responses can predict the strength of the bias. Overall, our findings support the existence of a dedicated, low-level perceptual mechanism involved with the computation of average numerosity, and highlight the processing stages involved with such process.
Magnitude processing and integration entail perceptual processes independent from the task
Authors: Togoli Irene , Collignon Olivier , Bueti Domenica , Fornaciai Michele 
Published: May 2024

ABSTRACTThe magnitude dimensions of visual stimuli, such as their numerosity, duration, and size, are intrinsically linked, leading to mutual interactions across them. However, it remains debated whether such interaction across dimensions, or “magnitude integration” effects, arise from low-level perceptual processes that are independent from the task performed, or whether they instead arise from high-level decision-making processes. We address this question with two experiments in which participants watched a series of dot-array stimuli modulated in numerosity, duration, and item size. In experiment 1 (task condition), the task required participants to either judge the numerosity, duration, or size of each stimulus. In experiment 2 (passive condition), instead, a separate group of participants passively watched the stimuli. The behavioral results obtained in the task show robust magnitude integration effects across all three dimensions. Then, we identify a neural signature of magnitude integration by showing that event-related potentials at several latency windows (starting at ∼100-200 ms after stimulus onset) can predict the effect measured behaviorally. In the passive condition, we demonstrate an almost identical modulation of brain responses, occurring at the same processing stages as during the task. Importantly, using a cross-condition multivariate decoding analysis, we demonstrate that brain responses to magnitude in the task condition can predict the response in the passive condition at specific latency windows. These results thus suggest that magnitude processing and integration likely occurs via automatic perceptual processes that are engaged irrespective of the task-relevance of the stimuli, and independently from decision making.
Augment Single-cell RNA-seq data with Surface Protein Levels using Gene set-based Deep Learning and Transfer Learning Methods
Authors: Hasib Md Musaddaqul , Zhang Tinghe , Zhang Jianqiu , Gao Shou-jiang , Huang Yufei 
Published: May 2024

AbstractAs scRNA-seq becomes increasingly accessible, providing a cost-efficient method to augment surface protein levels from gene expression measurements are desirable. We proposed a machine learning approach that includes a novel geneset neural network (GS-NN) that aims to learn robust and biologically meaningful features and a highly efficient transfer learning strategy to address cross-dataset differences. We conducted comprehensive experiments to show the improvements of the proposed methods. Specifically, we demonstrate that GS-NN learns more robust features to achieve better cross-subject performance than other machine learning approaches. Transfer learning further improves that of GS-NN by reducing dataset differences through highly efficient fine-tuning. The unique genesets design of GS-NN also allows identification of functions contributing to the prediction and improvement of the proposed strategy. Overall, this study reports a novel approach to robustly augment.Key PointsThe article presents a machine learning approach, Geneset Neural Network(GS-NN) to augment surface protein levels from single-cell RNA sequencing(scRNA-seq) gene expression data.The GS-NN aims to learn robust and biologically meaningful features, and the approach includes a highly efficient transfer learning strategy to address cross-dataset differences in scRNA-seq data.Comprehensive experiments demonstrate that GS-NN learns more robust features using trasfer learning techniques achieving better cross-subject performance compared to other machine learning approaches.The unique geneset-based architecture of GS-NN allows the identification and interpretion of biological functions contributing to the prediction of cell surface protein level.GS-NN’s architecture is conveniently transferrable across datasets, making it valuable tool for researchers working with diverse scRNA-seq datasets.
Physiological Processing of Aversiveness in the Mind’s Ear: Comparing Audiovisual, Auditory and Imagined Auditory Affective Stimuli
Authors: Yang Xuan , Oh Sewon , Stanley Jacob , Hammons Sarah , Anderson Ashley , Wedell Douglas H. , Shinkareva Svetlana V. 
Published: May 2024

AbstractUnderstanding the somatovisceral responses to auditory affective imagery has important implications in disorders like misophonia. The current study compared physiological responses to aversive and nonaversive states across three modalities: audiovisual, auditory, and auditory imagery. Electromyographic activity over corrugator supercilii (EMGc) and zygomaticus major (EMGz), electrodermal activity (EDA), heart rate (HR), and finger skin temperature (SKT) were measured. There was significant differentiation in EMGc, EDA, and HR deceleration between aversive and nonaversive audiovisual stimuli. EMGc potentiation was the only physiological measure showing consistent differentiation across the three modalities. Cross-modal aversiveness classification results revealed a similar physiological response pattern between audiovisual and auditory modalities. The physiological response pattern during auditory affective imagery was useful for predicting the aversiveness in audiovisual modality but not the other way around. Vividness in auditory imagery correlated with subjective hedonic valence ratings, but not physiological responses. Taken together, the current data suggest that the aversiveness of auditory imagery is differentiable in subjective affective experience and facial muscle potentiation. These results of the physiological responses to imagined aversive sounds in nonclinical population would serve as a comparison baseline for the study of misophonia.
Sodium-glucose co-transporter 2 Inhibitors Act Independently ofSGLT2to Confer Benefit for Heart Failure with Reduced Ejection Fraction in Mice
Authors: Berger Justin H. , Matsuura Timothy R. , Bowman Caitlyn E. , Taing Renee , Patel Jiten , Lai Ling , Leone Teresa C. , Reagan Jeffrey D. , Haldar Saptarsi M. , Arany Zoltan , Kelly Daniel P. 
Published: May 2024

AbstractSodium-glucose co-transporter 2 inhibitors (SGLT2i) are novel, potent heart failure medications with an unknown mechanism of action. We sought to determine if the beneficial actions of SGLT2i in heart failure were on- or off-target, and related to metabolic reprogramming, including increased lipolysis and ketogenesis. The phenotype of mice treated with empagliflozin and genetically engineered mice constitutively lacking SGLT2 mirrored metabolic changes seen in human clinical trials (including reduced blood glucose, increased ketogenesis, and profound glucosuria). In a mouse heart failure model, SGLT2i treatment, but not generalized SGLT2 knockout, resulted in improved systolic function and reduced pathologic cardiac remodeling. SGLT2i treatment of the SGLT2 knockout mice sustained the cardiac benefits, demonstrating an off-target role for these drugs. This benefit is independent of metabolic changes, including ketosis. The mechanism of action and target of SGLT2i in HF remain elusive.
AutoTA: Galaxy Workflows for Reproducible and Automated Taxonomic Analysis using Qiime2
Authors: Tikhe Atharva , Jangam Shweta , Arora Preeti , Gupte Sanjay , Shah Sarjan 
Published: May 2024

AbstractMetagenomic sequencing allows systematic characterization of microbial populations isolated from various environments of interest by bypassing the culturing of the isolates. Concomitant to advancement in sequencing techniques, analysis methods and softwares have also grown to be sophisticated and efficient. Qiime2 is a collection of python scripts which enables end-to-end analysis of metagenomic data. However, usage of latest and more complex databases for classification is hindered by requirement of high compute power. To aid cloud-based analysis, we present workflows for diversity analysis and taxonomic assignment which are the two most common and initial steps in a metagenomics experiments. The workflows are made in Galaxy which makes testing and analysing multiple datasets faster, in parallel, reproducible and flexible. The workflows can be integrated into a local Galaxy instance or used completely on the web which is of great importance to non-bioinformaticians and bench scientists.
Decoding the Language of Chickens - An Innovative NLP Approach to Enhance Poultry Welfare
Authors: Neethirajan Suresh 
Published: May 2024

AbstractThis research investigates the utilization of the Natural Language Processing-based WHISPER model for decoding chicken vocalizations, with the goal of comprehending the semantics and emotions embedded in their vocal communications. By leveraging advanced acoustic analysis techniques, the study focuses on interpreting the syntax and temporal patterns inherent in the vocalizations to discern the underlying affective states of chickens. This approach facilitates a non-invasive method of monitoring poultry welfare, enhancing traditional animal welfare assessments which often rely on direct human observation and can induce stress in the animals. The principal results from the application of the WHISPER model demonstrate its efficacy in classifying various chicken vocalizations into distinct categories that reflect specific emotional states such as distress, contentment, and fear. This classification is achieved by analyzing the frequency, duration, and intensity of vocalizations, thus providing a detailed insight into the emotional well-being of the animals. Our findings indicate that real-time monitoring of chicken vocalizations using NLP techniques can significantly improve the responsiveness and precision of welfare interventions. This method reduces the need for human interaction, minimizes stress for the animals, and allows for the continuous assessment of their well-being in a farming environment. Furthermore, the research highlights the potential of NLP tools in recognizing and interpreting complex animal vocalizations, which could lead to advancements in automated animal welfare monitoring systems. This study underscores the transformative potential of integrating sophisticated computational models like the WHISPER NLP model into animal welfare practices. By providing a more humane and efficient approach to monitoring animal welfare, this research contributes to the broader field of precision livestock farming, suggesting a shift towards more scientifically informed and welfare-centric farming practices. The application of such technologies not only aids in the immediate improvement of animal welfare but also supports sustainable farming operations by promoting the health and productivity of poultry through enhanced welfare standards.