bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Gaze, Vision, and Memory on Hand Kinematics in a Placement Task
Authors: Luabeya Gaelle N. , Yan Xiaogang , Freud Erez , Crawford J. Douglas 
Published: September 2023

ABSTRACTPeople usually reach for objects toplacethem in some position and orientation, but the placement component of this sequence is often ignored. For example, reaches are influenced by gaze position, visual feedback, and memory delays, but their influence on object placement is unclear. Here, we tested these factors in a task where participants placed and oriented a trapezoidal block against 2D visual templates displayed on a frontally located computer screen. In Experiment 1, participants matched the block to three possible orientations: 0° (horizontal), +45° and −45°, with gaze fixated 10° to the left/right. The hand and template either remained illuminated (closed-loop), or visual feedback was removed (open-loop). In Experiment 2, a memory delay was added, and participants sometimes performed saccades (centripetal, centrifugal, or opposite side). In Experiment 1, the hand consistently overshot the template relative to gaze (similar to reaching), especially in the open-loop task. After a memory delay, location errors were influenced by both template orientation and gaze position. Based on previous reach experiments, we expected these errors to be independent of the previous eye position, but placement overshoot also depended on previous saccade metrics. Hand orientation over-rotated relative to template orientation (all conditions). Orientation was influenced by gaze position in Experiment 1, but this vanished in the presence of a memory delay. These results demonstrate interactions between gaze, location, and orientation signals in the planning and execution of hand placement and suggest different neural mechanisms for closed-loop, open-loop, and memory delay placement.NEW & NOTEWORTHYEye-hand coordination studies usually focus on object acquisition, but placement is equally important. Here, we investigated how gaze position influences object placement toward a 2D template, with different levels of visual feedback. Like reach, placement overestimated goal location relative to gaze, but was also influenced by previous saccade metrics. Gaze also modulated hand orientation, which generally overestimated template orientation. Gaze influence was feedback-dependent, with location errors increasing but orientation errors decreasing after a memory delay.
Multifactorial approach is needed to unravel the maturation phases of human neurons derived from induced pluripotent stem cells
Authors: Ben Mahmoud Maissa , Rátkai Anikó , Bauer Krisztina , Bencsik Norbert , Szücs Attila , Schlett Katalin , Tárnok Krisztián 
Published: September 2023

AbstractNeurons derived from induced pluripotent stem cells (h-iPSC-Ns) provide an invaluable model for studying the physiological aspects of neuronal development and diseases. However, multiple studies have also demonstrated that h-iPSC-Ns exhibit a high degree of functional and epigenetic diversity. Due to the imprecise characterization and significant variation among the currently available maturation protocols, it is essential to establish a set of criteria to standardize models and accurately characterize and define the developmental properties of neurons derived from iPSCs.In this study, we conducted a comprehensive analysis of the h-iPSC-Ns via electrophysiological and microscopic techniques to follow their functional development at the cellular and network levels. This enabled us to provide a thorough description of the maturation process of h-iPSC-Ns over a 10-week periodin vitro. Specifically, we have used conventional whole-cell patch-clamp and dynamic clamp techniques, alongside morphometry, to assess the characteristics of maturing h-iPSC-Ns. Additionally, we utilized calcium imaging to monitor the progression of synaptic activity and network communication. At the single cell level, human neurons exhibited gradually decreasing membrane resistance in parallel with improved excitability by 5 weeks of maturation. Their firing profiles were consistent with those of mature regular firing type of neurons. At the network level we observed the development of abundant fast glutamatergic and depolarizing GABAergic synaptic connections together with synchronized network activity. The identified sequence of differentiation events are consistent and offers a robust framework for developing targeted experiments at varying stages of neuronal maturation. This framework allows for the use of different, age-related methodologies or a singular set of experiments for a culture’s maturation.
Mosquitoes do not like bitter: new perspectives for biorational repellents
Authors: Lazzari Claudio R. , Ortega-Insaurralde Isabel , Esnault Jérémy , Costa Eloïse , Crespo José E. , Barrozo Romina B. 
Published: September 2023

AbstractChemical repellents play a crucial role in personal protection, serving as essential elements in reducing the transmission of vector-borne diseases. A biorational perspective that extends beyond the olfactory system as the classical target may be a promising direction to move. The taste system provides reliable information regarding food quality, helping animals discriminate between nutritious and potentially harmful food sources, often associated with a bitter taste. Understanding how bitter compounds affect feeding in blood-sucking insects could unveil novel molecules with the potential to reduce biting and feeding. Here, we investigated the impact of two naturally occurring bitter compounds, caffeine and quinine, on the feeding decisions in femaleAedes aegyptimosquitoes at two distinctive phases: (1) when the mosquito explores the biting substrate using external taste sensors and (2) when the mosquito takes a sip of food and tastes it using internal taste receptors. We assessed the aversiveness of bitter compounds through both an artificial feeding condition (artificial feeder test) and a real host (arm-in-cage test). Our findings revealed different sensitivities in the external and internal sensory pathways responsible for detecting bitter taste inAe. aegypti. Internal detectors exhibited responsiveness to lower doses compared to the external sensors. Quinine exerted a more pronounced negative impact on biting and feeding activity than caffeine. The implications of our findings are discussed in the context of mosquito food recognition and the potential practical implications for personal protection.
KSHV 3.0: A State-of-the-Art Annotation of the Kaposi’s Sarcoma-Associated Herpesvirus Transcriptome Using Cross-Platform Sequencing
Authors: Prazsák István , Tombácz Dóra , Fülöp Ádám , Torma Gábor , Gulyás Gábor , Dörmő Ákos , Kakuk Balázs , Spires Lauren McKenzie , Toth Zsolt , Boldogkői Zsolt 
Published: September 2023

ABSTRACTKaposi’s sarcoma-associated herpesvirus (KSHV) is a large, oncogenic DNA virus belonging to the gammaherpesvirus subfamily. KSHV has been extensively studied with various high-throughput RNA-sequencing approaches to map the transcription start and end sites, the splice junctions, and the translation initiation sites. Despite these efforts, the comprehensive annotation of the viral transcriptome remains incomplete. In the present study, we generated a long-read sequencing dataset of the lytic and latent KSHV transcriptome using native RNA and direct cDNA sequencing methods. This was supplemented with CAGE sequencing based on a short-read platform. We also utilized datasets from previous publications for our analysis. As a result of this combined approach, we have identified a number of novel viral transcripts and RNA isoforms and have either corroborated or improved the annotation of previously identified viral RNA molecules, thereby notably enhancing our comprehension of the transcriptomic architecture of the KSHV genome. We also evaluated the coding capability of transcripts previously thought to be non-coding, by integrating our data on the viral transcripts with translatomic information from other publications.IMPORTANCEDeciphering the viral transcriptome of KSHV is of great importance because we can gain insight into the molecular mechanism of viral replication and pathogenesis, which can help develop potential targets for antiviral interventions. Specifically, the identification of substantial transcriptional overlaps by this work suggests the existence of a genome-wide interference between transcriptional machineries. This finding indicates the presence of a novel regulatory layer, potentially controlling the expression of viral genes.
Chitinase 3-like-1 (CHI3L1) in the Pathogenesis of Epidermal Growth Factor Receptor Mutant Non-Small Cell Lung Cancer
Authors: Kamle Suchitra , Ma Bing , Schor Gail , Bailey Madison , Pham Brianna , Cho Inyoung , Khan Hina , Azzoli Christopher , Hofstetter Mara , Lee Chang-Min , Herbst Roy , Politi Katerina , Lee Chun Geun , Elias Jack A. 
Published: September 2023

AbstractNon-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers. In NSCLC, 10-20% of Caucasian patients and 30-50% of Asian patients have tumors with activating mutations in the Epidermal Growth Factor Receptor (EGFR). A high percentage of these patients exhibit favorable responses to treatment with tyrosine kinase inhibitors (TKI). Unfortunately, a majority of these patients develop therapeutic resistance with progression free survival lasting 9-18 months. The mechanisms that underlie the tumorigenic effects ofEGFRand the ability of NSCLC to develop resistance to TKI therapies, however, are poorly understood. Here we demonstrate that CHI3L1 is produced by EGFR activation of normal epithelial cells, transformed epithelial cells with wild typeEGFRand cells with cancer-associated, activatingEGFRmutations. We also demonstrate that CHI3L1 auto-induces itself and feeds back to stimulate EGFR and its ligands. Highly specific antibodies against CHI3L1 (anti-CHI3L1/FRG) and TKI, individually and in combination, abrogated the effects of EGFR activation on CHI3L1 and the ability of CHI3L1 to stimulate the EGFR axis. Anti-CHI3L1 also interacted with osimertinib to reverse TKI therapeutic resistance and induce tumor cell death and inhibit pulmonary metastasis while stimulating tumor suppressor genes includingKEAP1. CHI3L1 is a downstream target of EGFR that feeds back to stimulate and activate the EGFR axis. Anti-CHI3L1 is an exciting potential therapeutic forEGFRmutant NSCLC, alone and in combination with osimertinib or other TKIs.
Asymmetric Contribution of a Selectivity Filter Gate in Triggering Inactivation of CaV1.3 Channels
Authors: del Rivero Morfin Pedro J. , Kochiss Audrey L. , Liedl Klaus R. , Flucher Bernhard E. , Fernández-Quintero Monica L.I. , Ben-Johny Manu 
Published: September 2023

AbstractVoltage-dependent and Ca2+-dependent inactivation (VDI and CDI, respectively) of CaVchannels are two biologically consequential feedback mechanisms that fine-tune Ca2+entry into neurons and cardiomyocytes. Although known to be initiated by distinct molecular events, how these processes obstruct conduction through the channel pore remains poorly defined. Here, focusing on ultra-highly conserved tryptophan residues in the inter-domain interfaces near the selectivity filter of CaV1.3, we demonstrate a critical role for asymmetric conformational changes in mediating VDI and CDI. Specifically, mutagenesis of the domain III-IV interface, but not others, enhanced VDI. Molecular dynamics simulations demonstrate that mutations in distinct selectivity filter interfaces differentially impact conformational flexibility. Furthermore, mutations in distinct domains preferentially disrupt CDI mediated by the N- versus C-lobes of CaM, thus uncovering a scheme of structural bifurcation of CaM signaling. These findings highlight the fundamental importance of the asymmetric arrangement of the pseudo-tetrameric CaVpore domain for feedback inhibition.
Neuroinflammation induces nerve growth factor dependent nociceptor sensitisation in a neonatal rodent model of platinum-based chemotherapy induced neuropathic pain
Authors: Da Vitoria Lobo Marlene , Hardowar Lydia , Valentine Tameille , Tomblin Lucy , Guest Charlotte , Sharma Dhyana , Paul-Clark Mark , Hulse Richard Philip 
Published: September 2023

AbstractChemotherapy-induced neuropathic pain (CINP) is a common adverse health related comorbidity that manifests later in life in paediatric patients treated for cancer. CIPN pathology progressively develops over time resulting in a delayed but long-lasting neuropathic pain. Current analgesic strategies are ineffective, aligning closely with our lack of understanding of CINP. Recent studies have indicated alterations in sensory neuronal maturation as component of CINP. The aim of this study was to investigate how cisplatin induces nerve growth factor mediated neuroinflammation and nociceptor sensitisation. In a rodent model of cisplatin induced survivorship pain, there was a significant infiltration of nerve growth factor positive macrophages into the dorsal root ganglia (DRG), demonstrating a robust neuroinflammatory response. Additionally, it was observed that CD11b/F480 positive monocyte/macrophages challenged with cisplatin expressed more NGF. Additionally, DRG derived primary sensory neuron cultures from neonatal mice demonstrated enhanced NGF-dependent TRPV1 mediated nociceptor activity after cisplatin treatment. Increased nociceptor activity was also observed when cultured neurons were treated with conditioned media from cisplatin activated monocyte/macrophages. This elevated nociceptor activity was dose-dependently inhibited by a neutralising monoclonal antibody to NGF. Intraperitoneal administration of NGF neutralising antibody significant reduction in mechanical hypersensitivity was given to mice with cisplatin-induced juvenile survivorship pain there was a as well as suppression of cisplatin induced aberrant nociceptor intraepidermal nerve fibre density. These findings identify the NGF/TrkA signalling pathway as a potential novel therapeutic target for analgesia in adult survivors of childhood cancer.
S100A8/A9 predicts triple-negative breast cancer response to PIM kinase and PD-1/PD-L1 inhibition
Authors: Begg Lauren R. , Orriols Adrienne M. , Zannikou Markella , Yeh Chen , Vadlamani Pranathi , Kanojia Deepak , Bolin Rosemary , Dunne Sara F. , Balakrishnan Sanjeev , Camarda Roman , Roth Diane , Zielinski-Mozny Nicolette A. , Yau Christina , Vassilopoulos Athanassios , Huang Tzu-Hsuan , Kim Kwang-Youn A. , Horiuchi Dai 
Published: September 2023

ABSTRACTIt remains elusive why some triple-negative breast cancer (TNBC) patients respond poorly to existing therapies while others respond well. Our retrospective analysis of historical gene expression datasets reveals that increased expression of immunosuppressive cytokine S100A8/A9 in early-stage tumors is robustly associated with subsequent disease progression in TNBC. Although it has recently gained recognition as a potential anticancer target, S100A8/A9 has not been integrated into clinical study designs evaluating molecularly targeted therapies. Our small molecule screen has identified PIM kinase inhibitors as capable of decreasing S100A8/A9 expression in multiple cell types, including TNBC and immunosuppressive myeloid cells. Furthermore, combining PIM inhibition and immune checkpoint blockade induces significant antitumor responses, especially in otherwise resistant S100A8/A9-high PD-1/PD-L1-positive tumors. Importantly, serum S100A8/A9 levels mirror those of tumor S100A8/A9 in a syngeneic mouse model of TNBC. Thus, our data suggest that S100A8/A9 could be a predictive and pharmacodynamic biomarker in clinical trials evaluating combination therapy targeting PIM and immune checkpoints in TNBC and encourage the development of S100A8/A9-based liquid biopsy tests.
Selection by differential survival among marine animals in the Phanerozoic
Authors: Tamre Erik , Parsons Christopher 
Published: September 2023

AbstractThe Gaia hypothesis posits that Earth’s biosphere functions as a single self-stabilizing system, but a key challenge is explaining how this could have arisen through Darwinian evolution. One theory is that of “selection by differential survival”, in which a clade’s extinction probability decreases with age as it accumulates adaptations resisting environmental disturbances. While this is hard to assess during early Earth history, we can assess whether this process operated among marine animal genera throughout the Phanerozoic. To that end, we analyzed time ranges of 36,117 extinct animal genera using fossil occurrence data from the Paleobiology Database in order to calculate marine metazoan extinction age selectivity, extinction rates, and speciation rates over the Phanerozoic. We identify four signatures of selection by differential survival: lower extinction rates among older lineages, heritability and taxonomically nested propagation of extinction resistance, reduced age selectivity during rare environmental perturbations, and differential extinction rather than speciation as the primary driver of the phenomenon. Evidence for this process at lower taxonomic levels also implies its possibility for life as a whole – indeed, the possibility of Gaia.
A haplotype-resolved chromosome-level assembly and annotation of European hazelnut (C. avellanacv. Jefferson) provides insight into mechanisms of eastern filbert blight resistance
Authors: Talbot S.C. , Vining K.J. , Snelling J.W. , Clevenger J. , Mehlenbacher S.A. 
Published: September 2023

AbstractEuropean hazelnut (Corylus avellanaL.) is an important tree nut crop. Hazelnut production in North America is currently limited in scalability due toAnisogramma anomala,a fungal pathogen that causes Eastern Filbert Blight (EFB) disease in hazelnut. Successful deployment of EFB resistant cultivars has been limited to the state of Oregon, where the breeding program at Oregon State University (OSU) has released cultivars with a dominant allele at a single resistance locus identified by classical breeding, linkage mapping, and molecular markers. ‘Jefferson’ is resistant to the predominant EFB biotype in Oregon and has been selected by the OSU breeding program as a model for hazelnut genetic and genomic research. Here, we present a near complete, haplotype-resolved chromosome-level hazelnut genome assembly forC. avellana‘Jefferson’. This new assembly is a significant improvement over a previously published genome draft. Analysis of genomic regions linked to EFB resistance and self-incompatibility confirmed haplotype splitting and identified new gene candidates that are essential for downstream molecular marker development, thereby facilitating breeding efforts.
Myocardial B cells have specific gene expression and predicted interactions in Dilated Cardiomyopathy and Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Bermea Kevin C. , Duque Carolina , Cohen Charles D. , Bhalodia Aashik , Rousseau Sylvie , Lovell Jana , Zita Marcelle Dina , Mugnier Monica R. , Adamo Luigi 
Published: September 2023

ABSTRACTIntroductionGrowing evidence from animal models indicates that the myocardium hosts a population of B cells that play a role in the development of cardiomyopathy. However, there is minimal data on human myocardial B cells in the context of cardiomyopathy.MethodsWe integrated single-cell and single-nuclei datasets from 45 healthy human hearts, 70 hearts with dilated cardiomyopathy (DCM), and 8 hearts with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC). Interactions between B cells and other cell types were investigated using the CellChat Package. Differential gene expression analysis comparing B cells across conditions was performed using DESeq2. Pathway analysis was performed using Ingenuity, KEGG, and GO pathways analysis.ResultsWe identified 1,100 B cells, including naive B cells and plasma cells. B cells showed an extensive network of interactions within the healthy myocardium that included outgoing signaling to macrophages, T cells, endothelial cells, and pericytes, and incoming signaling from endothelial cells, pericytes, and fibroblasts. This niche relied on ECM-receptor, contact, and paracrine interaction; and changed significantly in the context of cardiomyopathy, displaying disease-specific features. Differential gene expression analysis showed that in the context of DCM both naive and plasma B cells upregulated several pathways related to immune activation, including upregulation of oxidative phosphorylation, upregulation of leukocyte extravasation, and, in naive B cells, antigen presentation.DiscussionThe human myocardium contains naive B cells and plasma cells, integrated into a diverse and dynamic niche that has distinctive features in healthy myocardium, DCM, and ARVC. Naive myocardial-associated B cells likely contribute to the pathogenesis of human DCM.
Precise Alterations in Hippocampal Neural Deterioration and Neural Correlates of Visual Short-Term Memory in Individuals with Amnestic Mild Cognitive Impairment
Authors: Xie Ye , Zhao Tinghao , Li Yunxia , Ku Yixuan 
Published: September 2023

AbstractPurposeAtrophy of the hippocampus is an early biomarker of Alzheimer’s disease (AD) and a main contributor to the patients’ mnemonic degeneration. While previous research has mostly focused on how hippocampal atrophy impaired long-term memory performance, its relation to short-term memory impairment, which was also found among patients with AD, remains largely uninvestigated. Filling this gap, the current study examined how atrophy in the hippocampus and its subfields may have influenced visual short-term memory (VSTM) in patients with amnestic mild cognitive impairment (aMCI), a common precursor of AD.MethodsFifty-eight aMCI patients and 69 healthy controls (HC) matched in age were included in the current study. VSTM was assessed using an adapted change detection task with a memory load of 2 or 4 items. Hippocampal subfields were automatically segmented in T1-weighted image using FreeSurfer and were manually inspected for errors. Volumes of the subfields were extracted and compared between aMCI and HC subjects using ANCOVA with age, gender and education as covariates. Furthermore, we also examined the partial correlation between VSTM performances and hippocampal subfield volumes with age, gender and education as covariates.ResultsCompared to HC subjects, aMCI subjects had lower response accuracy (ACC) and lower memory capacity under both load conditions and had longer reaction time (RT) in the 2-load condition. Left hippocampus volume was significantly smaller in aMCI and was positively correlated with ACC and capacity in HC but not in aMCI. Among the hippocampal subfields, left hippocampal tail, left molecular layer, left dentate gyrus (DG), left CA4, bilateral subiculum, bilateral presubiculum, bilateral fimbria, were significantly smaller while right hippocampal fissure was significantly widened in aMCI compared to HC. Volumes of the left subiculum, left molecular layer, left DG and left CA4 were positively correlated with ACC and capacity in HC but not in aMCI. Bilateral fimbria volume was negatively correlated with RT under the 2-load condition in HC but not in aMCI.ConclusionThe results of this study suggested that hippocampal deterioration, especially in subfields related to information input and output (e.g. molecular layer, DG, subiculum), may have contributed to VSTM impairment in aMCI by disrupting hippocampal-cortical communications. This finding adds to increasing evidence of hippocampal engagement in short-term memory processes and points to VSTM impairment as a potential neuropsychological indicator for MCI and AD.