bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fluidic shear stress alters clathrin dynamics and vesicle formation in endothelial cells
Authors: Nawara Tomasz J. , Sztul Elizabeth , Mattheyses Alexa L. 
Published: January 2024

AbstractEndothelial cells (ECs) experience a variety of highly dynamic mechanical stresses. Among others, cyclic stretch and increased plasma membrane tension inhibit clathrin-mediated endocytosis (CME) in non-ECs cells. How ECs overcome such unfavorable, from biophysical perspective, conditions and maintain CME remains elusive. Previously, we have used simultaneous two-wavelength axial ratiometry (STAR) microscopy to show that endocytic dynamics are similar between statically cultured human umbilical vein endothelial cells (HUVECs) and fibroblast-like Cos-7 cells. Here we asked whether biophysical stresses generated by blood flow could favor one mechanism of clathrin-coated vesicle formation to overcome environment present in vasculature. We used our data processing platform – DrSTAR – to examine if clathrin dynamics are altered in HUVECs grown under fluidic sheer stress (FSS). Surprisingly, we found that FSS led to an increase in clathrin dynamics. In HUVECs grown under FSS we observed a 2.3-fold increase in clathrin-coated vesicle formation and a 1.9-fold increase in non-productive flat clathrin lattices compared to cells grown in static conditions. The curvature-positive events had significantly delayed curvature initiation in flow-stimulated cells, highlighting a shift toward flat-to-curved clathrin transitions in vesicle formation. Overall, our findings indicate that clathrin dynamics and CCV formation can be modulated by the local physiological environment and represents an important regulatory mechanism.SignificanceTargeted nanomedicine holds a great promise of improved drug bioavailability and specificity. While some cargoes must cross the blood-tissue barrier, the understanding of endocytic pathways in the context of vasculature is limited, which is an obstacle to targeted nanomedicine delivery. In this pilot study we show that the physiological local vascular environment must be considered in the context of internalization of growth factors, membrane proteins, therapeutics, or pathogens. Studies in non-ECs or ECs not cultured under fluidic shear stress do not properly recapitulate clathrin dynamics and will lead to incorrect conclusions.
Invasion of glioma cells through confined space requires membrane tension regulation and mechano-electrical coupling via Plexin-B2
Authors: Alves Chrystian Junqueira , Hannah Theodore , Sadia Sita , Kolsteeg Christy , Dixon Angela , Wiener Robert J. , Nguyen Ha , Tipping Murray J. , Ladeira Júlia Silva , Franklin Paula Fernandes da Costa , Dutra de Nigro Nathália de Paula , Dias Rodrigo Alves , Zabala Capriles Priscila V. , Rodrigues Furtado de Mendonça José P. , Slesinger Paul , Costa Kevin , Zou Hongyan , Friedel Roland H. 
Published: January 2024

ABSTRACTGlioblastoma (GBM) is a malignant brain tumor with uncontrolled invasive growth. Here, we demonstrate how GBM cells usurp guidance receptor Plexin-B2 to gain biomechanical plasticity for polarized migration through confined space. Using live-cell imaging to track GBM cells negotiating microchannels, we reveal active endocytosis at cell front and filamentous actin assembly at rear to propel GBM cells through constrictions. These two processes are interconnected and governed by Plexin-B2 that orchestrates cortical actin and membrane tension, shown by biomechanical assays. Molecular dynamics simulations predict that balanced membrane and actin tension are required for optimal migratory velocity and consistency. Furthermore, Plexin-B2 mechanosensitive function requires a bendable extracellular ring structure and affects membrane internalization, permeability, phospholipid composition, as well as inner membrane surface charge. Together, our studies unveil a key element of membrane tension and mechanoelectrical coupling via Plexin-B2 that enables GBM cells to adapt to physical constraints and achieve polarized confined migration.
Distinct profiles of tinnitus and hyperacusis in intensity deviant responses and auditory evoked potentials
Authors: Yukhnovich Ekaterina A , Alter Kai , Sedley William 
Published: January 2024

AbstractERPs in response to intensity deviant stimuli are assessed in four age and hearing matched groups of various combinations of tinnitus and hyperacusis (both conditions, one of the conditions, neither condition). Distinct profiles for tinnitus and hyperacusis are shown, as well as additional more nuanced interactions. This not only moves our understanding of each condition, but also speaks directly to possible mechanistic subtypes of tinnitus (and of hyperacusis) which might be disentangled through the cheap and available technique that is single-channel EEG. The current findings may also explain some discrepant findings in past literature.
Increased inflammatory signature in myeloid cells of non-small cell lung cancer patients with high clonal hematopoiesis burden
Authors: Sim Hyungtai , Park Hyun Jung , Park Geun-Ho , Kim Yeon Jeong , Park Woong-Yang , Lee Se-Hoon , Choi Murim 
Published: January 2024

AbstractClonal hematopoiesis of indeterminate potential (CHIP) allows estimation of clonal dynamics and documentation of somatic mutations in the hematopoietic system. Recent studies utilizing large cohorts of the general population and patients have revealed significant associations of CHIP burden with age and disease status, including in cancer and chronic diseases. An increasing number of cancer patients are treated with immune checkpoint inhibitors (ICI), but the association of ICI response in non-small cell lung cancer (NSCLC) patients with CHIP burden remains to be determined. We collected blood samples from 100 metastatic NSCLC patients before and after ICI for high-depth sequencing of the CHIP panel and 63 samples for blood single-cell RNA sequencing(scRNA-seq). Whole exome sequencing (WES) was performed in an independent replication cohort of 180 patients. The impact of CHIP status on the immunotherapy response was not significant. However, metastatic lung cancer patients showed higher CHIP prevalence (44/100 for patients vs 5/42 for controls;P= 0.01). In addition, lung squamous cell carcinoma patients showed increased burden of larger clones compared to lung adenocarcinoma patients (8/43 for LUSC vs 2/50 for LUAD;P= 0.04). Furthermore, single cell RNA-seq analysis of the matched patients showed significant enrichment of inflammatory pathways mediated by NF-ĸB in myeloid clusters of the severe CHIP group. Our findings suggest minimal involvement of CHIP mutation and clonal dynamics during immunotherapy but a possible role of CHIP as an indicator of immunologic response in NSCLC patients.
De novo multi-mechanism antimicrobial peptide design via multimodal deep learning
Authors: Wang Yue , Gong Haifan , Li Xiaojuan , Li Lixiang , Zhao Yinuo , Bao Peijing , Kong Qingzhou , Wan Boyao , Zhang Yumeng , Zhang Jinghui , Ni Jiekun , Han Zhongxue , Nan Xueping , Ju Kunping , Sun Longfei , Chang Huijun , Zheng Mengqi , Yu Yanbo , Yang Xiaoyun , Zuo Xiuli , Li Yanqing 
Published: January 2024

ABSTRACTArtificial intelligence (AI)-driven discovery of antimicrobial peptides (AMPs) is yet to fully utilise their three-dimensional (3D) structural characteristics, microbial specie-specific antimicrobial activities and mechanisms. Here, we constructed a QLAPD database comprising the sequence, structures and antimicrobial properties of 12,914 AMPs. QLAPD underlies a multimodal, multitask, multilabel, and conditionally controlled AMP discovery (M3-CAD) pipeline, which is proposed for thede novodesign of multi-mechanism AMPs to combat multidrug-resistant organisms (MDROs). This pipeline integrates the generation, regression, and classification modules, using a innovative 3D voxel coloring method to capture the nuanced physicochemical context of amino acids, significantly enhancing structural characterizations. QL-AMP-1, discovered by M3-CAD, which possesses four antimicrobial mechanisms, exhibited low toxicity and significant activity against MDROs. The skin wound infection model demonstrates its considerable antimicrobial effects and negligible toxicity. Altogether, integrating 3D features, specie-specific antimicrobial activities and mechanisms enhanced AI-driven AMP discovery, making the M3-CAD pipeline a viable tool forde novoAMP design.
BCI Toolbox: An Open-Source Python Package for the Bayesian Causal Inference Model
Authors: Zhu Haocheng , Beierholm Ulrik , Shams Ladan 
Published: January 2024

AbstractPsychological and neuroscientific research over the past two decades has shown that the Bayesian causal inference (BCI) is a potential unifying theory that can account for a wide range of perceptual and sensorimotor processes in humans. Therefore, we introduce the BCI Toolbox, a statistical and analytical tool in Python, enabling researchers to conveniently perform quantitative modeling and analysis of behavioral data. Additionally, we describe the algorithm of the BCI model and test its stability and reliability via parameter recovery. The present BCI toolbox offers a robust platform for BCI model implementation as well as a hands-on tool for learning and understanding the model, facilitating its widespread use and enabling researchers to delve into the data to uncover underlying cognitive mechanisms.
Metabolome and transcriptome profiling of root chicory provide insights into laticifer development and specialized metabolism
Authors: Vahabi Khabat , Balcke Gerd U. , Hakkert Johanna C. , van der Meer Ingrid M. , Athmer Benedikt , Tissier Alain 
Published: January 2024

AbstractChicory roots produce inulin, a dietary fiber, as well as large quantities of bitter sesquiterpene lactones (STLs), which have valuable biological activities. In an effort to understand the compartmentalization of metabolism within chicory roots and the molecular basis of the development of laticifers that produce the chicory latex, we performed metabolomics and transcriptomics profiling. GC-MS and LC-MS identified a total of 22 580 features of which 135 were differentially abundant between cell types. Further analysis indicated that the major STLs accumulated primarily in the latex. Gene expression of known STL pathway genes indicates a compartmentalization of the biosynthesis across multiple tissues, with implications regarding the trafficking of pathway intermediates. Phytohormone measurements and gene expression analysis point to a major role for jasmonate signaling in the development and differentiation of laticifers. Furthermore, inulin accumulates mostly outside the laticifers but expression of inulin metabolic genes also point to a complex distribution and trafficking of inulin or inulin precursors across different root compartments. Altogether, the data presented here constitute a unique resource to investigate several biological processes in chicory roots, including laticifer development, STL biosynthesis and transport and inulin biosynthesis regulation.Significance statementA combination of transcriptomics, targeted and untargeted metabolomics of different tissues of chicory roots was generated. These data constitute a resource basis for the investigation of various processes taking place in chicory taproots, including sesquiterpene lactone biosynthesis, laticifer development and inulin biosynthesis and trafficking.
Alzheimer’s disease copathology in dementia with Lewy bodies is associated with astroglial α-synucleinopathy
Authors: Geut Hanne , van den Berg Emma , Boon Baayla D.C. , Hoozemans Jeroen J.M. , Tunold Jon-Anders , Pihlstrøm Lasse , Jonkman Laura E. , Rozemuller J.M. Annemieke , Lemstra A.W. Evelien , van de Berg Wilma D.J. 
Published: January 2024

AbstractBackgroundIn dementia with Lewy bodies (DLB), co-existence of Alzheimer’s disease (AD) pathology, i.e. amyloid-β plaques and tau tangles, has been associated with a more rapid disease progression. In post-mortem DLB brains, we examined the association between AD copathology and regional load and morphology of α-synuclein pathology. Also, we compared regional load and morphology of AD copathology in DLB to pathology in AD.MethodsWe included 50 autopsy-confirmed DLB donors with a clinical DLB phenotype, categorized as having no/low levels of AD copathology (pure DLB,n= 15), or intermediate/high levels of AD copathology (mixed DLB+AD,n= 35), and autopsy-confirmed pure AD donors (n= 14) without α- synuclein pathology. We used percentage area of immunopositivity for quantitative assessment of pathology load, and visual scores for semi-quantitative assessment of different morphologies of α- synuclein, amyloid-β and phosphorylated tau (p-tau) pathology in fifteen neocortical, limbic and brainstem regions.ResultsMixed DLB+AD compared to pure DLB showed a shorter disease duration (6 ± 3 versus 8 ± 3 years,p= 0.021) and higher frequency ofAPOE-ε4 alleles. A-synuclein load was higher in neocortical regions (temporal, parietal and occipital), but not in brainstem and limbic regions, which was based upon an increase of Lewy bodies, α-synuclein-positive astrocytes and α-synuclein-positive plaques in these regions. A-synuclein load was most strongly correlated to amyloid-β and p-tau load in temporal (r= 0.38 andr= 0.50 respectively) and occipital regions (r= 0.43 andr= 0.42 respectively). Compared to pure AD, mixed DLB+AD showed a lower amyloid-β load in temporal cortex, CA3 and CA4 region, and lower p-tau loads in frontal and parietal cortex, based both upon presence of fewer neuritic plaques as well as neurofibrillary tangles.ConclusionsIn DLB brains, AD copathology was associated with more neocortical α-synuclein pathology, consisting not only of Lewy bodies and plaques, but also of astroglial α-synuclein. AD pathology in DLB cases is less than in AD cases, reflecting less advanced pathological stages. Astroglial α-synuclein and its relation with AD copathology in DLB should be further studied, as this may play a role in accelerating clinical decline.
Effects of joint invasion: how co-invaders affect each other’s success in model food webs?
Authors: Móréh Ágnes , Jordán Ferenc , Scheuring István 
Published: January 2024

ABSTRACTWhile there is considerable research on interactions between invasive and native species, as well as on the impact of invasive species on the resident community, less focus has been placed on exploring the relationship and interactions among invasive species themselves. Nevertheless, it is widely acknowledged that invasive species can have either positive or negative effects on one another’s success, in addition to neutral outcomes. In the present theoretical study, we compared the success of two invasive non-native species in two scenarios: when they invaded the resident food web separately and simultaneously. We investigated the correlations between their direct and indirect ecological relationships and the topological positions of them in the food web, with the varying outcomes of joint invasion. Using the allometric bioenergetic model (ABM) for dynamical simulations, we detected the success of invasion (presence or absence of invaders) and the direction of their biomass change comparing separated and simultaneous invasion scenarios. We studied the relationships among these variables after detailed numerical simulations with variable key parameters of the model.We found that direct and indirect ecological relationships between the two invaders are significantly modifies the invasion scenarios: the predator-prey relationship increases the probability of invasion success for both invaders, but the equilibrium biomass of at least one of them is more likely to be reduced than in separate invasions. The trophic cascade or competitive relationship between them during simultaneous invasion also affects their success rate, with the former having a positive effect and the latter a negative one. Further, we found that higher trophic level and lower betweenness centralities of the invaders reduces the likelihood of invasion success regardless of the presence or absence of another invasive species. The results of the study can be tested experimentally in micro- and mesocosms.HIGHLIGHTSIn a joint invasion, invaders can influence each other’s successPredator-prey relationships between invaders increase the joint invasion successCompetition increases the failure of at least one invaderThe trophic cascade between invaders increases the joint invasion successHigher trophic levels or lower betweenness centralities of the invaders increase the probability of unsuccessful joint invasionGRAPHICAL ABSTRACT
Thermogenetics for cardiac pacing
Authors: Balatskiy Alexander V. , Nesterenko Alexey M. , Lanin Aleksandr A. , Ovechkina Vera S. , Sabinin Semyon S. , Fetisova Elena S. , Moshchenko Alexander A. , Jappy David , Sokolov Rostislav A. , Biglova Diana Z. , Solius Georgy M. , Solyus Ekaterina M. , Korolev Sergei V. , Podgorny Oleg V. , Kelmanson Ilya V. , Rozov Andrei V. , Fedotov Andrei B. , Bruegmann Tobias , Zheltikov Alexei M. , Mozhaev Andrey A. , Belousov Vsevolod V. 
Published: January 2024

AbstractCardiac arrhythmias are common disorders that can be fatal. Modern methods of treating bradyarrhythmias include the implantation of pacemakers and cardioverters – defibrillators. However, the implantable devices can cause various complications including infectious ones, related to the electrodes installed inside the heart. Less invasive heart rhythm modulation could be beneficial for some cohorts of patients. We present an alternative approach to heart pacing based on thermogenetics. We used adeno-associated viruses to deliver genetic human transient receptor potential subfamily V member 1 (TRPV1), a heat-sensitive cation channel, into isolated cardiomyocytes and the mouse heart. This allowed us to induce action potentials and control contractility using short heat pulses delivered by infrared laser illumination. Using this approach, we demonstrated the thermogenetic pacing of isolated cardiomyocytesin vitroand in the mouse heartin vivo. Our results demonstrate the unique potential of thermogenetics for developing novel therapeutic strategies for heart rhythm modulation.
The opossum and other didelphids in the cultures of Costa Rican society and indigenous peoples: an approach to ecology and conservation
Authors: Romero Yara Azofeifa , Alvarado Francisco Durán 
Published: January 2024

ABSTRACTThe opossumDidelphis marsupialis, commonly referred to as thezorro pelónin Costa Rica, is a marsupial that holds significant representation in both Costa Rican and indigenous cultures, such as the Talamanca natives. This species, along with the other ten opossums found in Costa Rica, constitute one of the groups of mammals with the least representation in scientific literature. This study aims to (1) document the knowledge, uses, perceptions, and human-zorro pelóninteractions through surveys conducted with individuals in three types of zones: rural, semi-urban, and urban; and (2) explore the presence of opossums in the 19th-century worldview of farmers and in the cosmovision of indigenous peoples. We performed an analysis on the text and Likert-scale data collected from 296 surveys conducted across seven provinces in Costa Rica. Nonparametric tests were conducted to assess whether the type of zone influenced the interactions and perceptions of individuals. Valuable information was obtained from key participants and informants regarding the behavior, observation sites, diet, and population trends of the species. The remarkable adaptability of thezorro pelónis evident in rural and semi-urban environments, but not in urban zones. The human-zorro pelóninteraction data between the rural and semi-urban zones are similar, but these differ significantly from the urban zone. Although people surveyed generally have a positive perception of the opossum, there has been a notable devaluation over time when compared to the imaginary of indigenous cultures. Parallels were observed in the beliefs and uses of marsupials between pre-Columbian societies and contemporary Costa Rican societies. As part of the educational strategies for the conservation of marsupials, it is important to promote their appreciation and refute negative stereotypes, such as by informing about their ecological role and their ability to resist pathogens and venom. In this context, the rich symbolism of the opossum can be utilized to adapt the message to the various regions of America.
Intensity mismatch asymmetry in tinnitus – in which direction should participants pay attention?
Authors: Yukhnovich Ekaterina A , Alter Kai , Sedley William 
Published: January 2024

AbstractThe effects attention has on intensity deviant Mismatch Negativity responses is an unknown factor in basic sensory neuroscience. It would be useful to understand how attention would affect responses to intensity deviants compared to each other (upward vs downward), and compared to other sensory dimensions such as frequency. Overall, previous research indicates that attention may modulate neuronal gain in healthy participants and change the amplitudes of evoked responses, and may mainly affect the responses to regularly repeating (standard) stimuli rather than deviants. Gain may respond differently in participants with tinnitus and/or hyperacusis under the same conditions compared to controls. Overall, results of the passive task condition were consistent with previous research. Auditory attention magnified MMN in response to upward deviants, while visual attention attenuated it in both control and tinnitus groups. However, auditory attention selectively enhanced downward deviant MMN in the tinnitus group (compared to passive attention). Using the auditory attention paradigm may be advantageous in MMN studies on tinnitus/hyperacusis because the observed differences would be particularly large.
Direct interrogation of context-dependent GPCR activity with a universal biosensor platform
Authors: Janicot Remi , Maziarz Marcin , Park Jong-Chan , Luebbers Alex , Green Elena , Zhao Jingyi , Philibert Clementine , Zhang Hao , Layne Mathew D. , Wu Joseph C. , Garcia-Marcos Mikel 
Published: January 2024

ABSTRACTG protein-coupled receptors (GPCRs) are the largest family of druggable proteins in the human genome, but progress in understanding and targeting them is hindered by the lack of tools to reliably measure their nuanced behavior in physiologically-relevant contexts. Here, we developed a collection of compactONEvectorG-proteinOptical (ONE-GO) biosensor constructs as a scalable platform that can be conveniently deployed to measure G-protein activation by virtually any GPCR with high fidelity even when expressed endogenously in primary cells. By characterizing dozens of GPCRs across many cell types like primary cardiovascular cells or neurons, we revealed new insights into the molecular basis for G-protein coupling selectivity of GPCRs, pharmacogenomic profiles of anti-psychotics on naturally-occurring GPCR variants, and G-protein subtype signaling bias by endogenous GPCRs depending on cell type or upon inducing disease-like states. In summary, this open-source platform makes the direct interrogation of context-dependent GPCR activity broadly accessible.