bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial autocorrelation dimension as a potential determinant for the temporal persistence of human atrial and ventricular fibrillation
Authors: Dharmaprani Dhani , Jenkins Evan V. , Quah Jing X. , Tiver Kathryn , Mitchell Lewis , Tung Matthew , Ahmad Waheed , Stoyanov Nik , Aguilar Martin , Nash Martyn P. , Clayton Richard H. , Nattel Stanley , Ganesan Anand N. 
Published: April 2023

ABSTRACTBackground:Despite being central to atrial fibrillation (AF) and ventricular fibrillation (VF) mechanisms and therapy, the factors governing AF and VF termination are poorly understood. It has been noted that ratio of system size (L) and the two-point spatial correlation length (ξ2) are associated with time until termination in transient spatiotemporally chaotic systems, but the relationship between these characteristics and termination has not been systematically studied in human AF and VF.Objective:We aimed assess whether the time to cardiac fibrillation termination can be predicted using a novel estimator, the spatial autocorrelation dimension (Di), defined as the ratio ofLand ξ2, in human AF and VF.Methods:Diwas computed and compared in a multi-centre, multi-system study with data for sustained versus spontaneously terminating human AF/VF. VF data was collected during coronary-bypass surgery; and AF data during clinically indicated AF ablation. We analyzed: i) VF mapped using a 256-electrode epicardial sock (n=12pts); ii) AF mapped using a 64-electrode constellation basket-catheter (n=15pts); iii) AF mapped using a 16-electrode HD-grid catheter (n=42pts). To investigate temporal fibrillation persistence, the response of AF-episodes to flecainide (n=7pts) was also studied.Results:Spontaneously terminating fibrillation demonstrated a lowerDi(P<0.001 all systems). LowerDiwas also seen in paroxysmal compared to persistent AF (P=0.002). Post-flecainide,Didecreased over time (P<0.001). LowerDiwas also associated with longer-lasting episodes of AF/VF (R2>0.90, P<0.05 in all cases). Using k-means clustering, two distinct clusters and their centroids were identified i) a cluster of spontaneously terminating episodes, and ii) a cluster of sustained epochs.Conclusion:Dipredicts the temporal persistence of cardiac fibrillation. This finding provides potentially important insights into a possible common pathway to termination and therapeutic approaches.
Endocardial HDAC3 is required for myocardial trabeculation
Authors: Jang Jihyun , Bentsen Mette , Kim Ye Jun , Kim Erick , Garg Vidu , Cai Chen-Leng , Looso Mario , Li Deqiang 
Published: April 2023

AbstractFailure of proper ventricular trabeculation is often associated with congenital heart disease (CHD). Support from endocardial cells, including the secretion of extracellular matrix (ECM) and growth factors is critical for trabeculation. However, it is poorly understood how the secretion of ECM and growth factors is initiated and regulated by endocardial cells.We found that genetic knockout (KO) of histone deacetylase 3 (Hdac3) in the endocardium in mice resulted in early embryo lethality and ventricular hypotrabeculation. Single cell RNA sequencing identified significant downregulation of ECM components inHdac3KO endocardial cells. Secretome from culturedHdac3KO mouse cardiac endothelial cells lacked transforming growth factor ß3 (TGFß3) and showed significantly reduced capacity in stimulating cultured cardiomyocyte proliferation, which was remarkably rescued by TGFß3 supplementation. Mechanistically, we identified that HDAC3 inducedTgfß3expression through repressing microRNA (miR)-129-5p.Our findings provide novel insights into the pathogenesis of CHD and conceptual strategies to promote myocardial regeneration.
Understanding inter-individual social networks in mixed-species bird flocks
Authors: Bharadwaj Akshay , Thapa Aiti , Bhat Akshiti , Biswakarma Aman , Tamang Bharath , Munda Binod , Biswakarma Biren , Pradhan Dambar K , Tamang Dema , Pradhan Kabir , Rai Mangal K , Rai Pawan Chamling , Rai Rohit , Rai Shambu , Srinivasan Umesh 
Published: April 2023

AbstractMixed-species flocks (MSFs) are an important form of social organisation in forest bird communities worldwide. MSFs provide participants with the benefits of reduced predation risk and/or enhanced foraging efficiency. Recent work has shown that participation in MSFs confers long-term survival benefits in the face of anthropogenic change. However, our understanding of MSFs mainly comes from studies that examine species-level networks, where each node is a unique species and the edges or connections between nodes are associations/interactions between species. While valuable, such approaches might not allow us to understand and investigate the mechanisms that drive MSF formation and structure because social interactions and their effects occur at the individual-level. Empirical studies on multi-species, individual-level MSF social networks have seldom been undertaken due to the various complexities and logistical challenges involved. In this study, we use mist-netting and colour-ringing followed by a standardised observation protocol to construct individual-level social networks in MSFs at 2000m ASL in Eaglenest Wildlife Sanctuary, Arunachal Pradesh, Eastern Himalaya, India. First, we found two separate flocktypes at our study site, comprising two distinct sets of understorey species. The mechanisms contributing to individual-level co-occurrences are likely to differ between these flocktypes, and with MSFs in the Neotropics. The Rusty-fronted Barwing (the nuclear species of one flocktype) shows spatially disjunct territories for each flock while the Yellow-throated Fulvetta (nuclear species of the other flocktype) shows large spatial overlap in its MSF networks, which is likely driven by non-individual-specific benefits such as predation risk dilution. Further, the addition of associating individuals to the social networks has opposite impacts on the two networks. The addition of Coral-billed Scimitar Babblers to the barwing networks greatly reduces network modularity because the associating individuals bridge two modules of barwings (both spatially and in the social network). On the contrary, territorial Rufous-capped Babblers and Grey-cheeked Warblers increase the modularity of the spatially overlapping fulvetta network. Our study provides novel insights into flock formation mechanisms in the Eastern Himalaya, likely applicable to other multi-species flock systems in the Old World.
Amoeboid cells undergo durotaxis with soft end polarized NMIIA
Authors: Kang Chenlu , Chen Pengcheng , Yi Xin , Li Dong , Hu Yiping , Yang Yihong , Cai Huaqing , Li Bo , Wu Congying 
Published: April 2023

AbstractCell migration towards stiff substrates has been coined as durotaxis and implicated in development, wound healing and cancer, where complex interplays between immune and non-immune cells are present. Compared to the emerging mechanisms underlying the strongly adhesive mesenchymal durotaxis, little is known about whether immune cells - migrating in amoeboid mode - could follow mechanical cues. Here we develop an imaging-based confined migration device with stiffness gradient. By tracking live cell trajectory and analyzing the directionality of T cells and neutrophils, we observe that amoeboid cells can durotax. We further delineate the underlying mechanism to involve non-muscle myosin IIA (NMIIA) polarization towards the soft-matrix-side but may not require differential actin flow up- or down-stiffness gradient. Using the protistaDictyostelium, we demonstrate the evolutionary conservation of amoeboid durotaxis. Finally, these experimental phenomena are theoretically captured by an active gel model capable of mechanosensing. Collectively, these results may shed new lights on immune surveillance and recently identified confined migration of cancer cells, within the mechanically inhomogeneous tumor microenvironment or the inflamed fibrotic tissues.
Wide scope analysis of bioactive lipids, including steroids, bile acids, and polyunsaturated fatty acid metabolites, in human plasma by LC/MS/MS
Authors: Nakatani Kohta , Izumi Yoshihiro , Umakoshi Hironobu , Yokomoto-Umakoshi Maki , Nakaji Tomoko , Kaneko Hiroki , Nakao Hiroshi , Ogawa Yoshihiro , Ikeda Kazutaka , Bamba Takeshi 
Published: April 2023

AbstractQuantitative information on blood metabolites has the potential to be utilized in medical strategies such as early disease detection and prevention. Monitoring of bioactive lipids, such as steroids, bile acids, and polyunsaturated fatty acid (PUFA) metabolites, could be a valuable indicator for health status. However, a method for simultaneous measurement of these bioactive lipids has not been reported at present. Here, we report a liquid chromatography tandem mass spectrometry (LC/MS/MS) method that can simultaneously measure more than 140 bioactive lipids, including steroids, bile acids, and PUFA metabolites, from human plasma, and a sample preparation method for these targets. Protein removal in methanol precipitation and purification operations of bioactive lipids by solid-phase extraction improved the recovery of targeted compounds in human plasma samples, demonstrating the importance of sample preparation methods in a wide range of bioactive lipid analyses. Using the developed method, we measured plasma from healthy human volunteers and confirmed the presence of bioactive lipid molecules associated with sex differences and circadian rhythms. The practical bioactive lipid analysis method developed is expected to be applied to health monitoring and disease biomarker discovery for precision medicine.
Sugar feeding by invasive mosquito species on ornamental and wild plants
Authors: Upshur Irving Forde , Fehlman Mikhyle , Parikh Vansh , Lahondère Chloé 
Published: April 2023

AbstractFeeding on plant-derived sugars is an essential component of mosquito biology that affects key aspects of their lives such as survival, metabolism, and reproduction. Mosquitoes locate plants to feed on using olfactory and visual cues.Aedes aegyptiandAedes albopictusare two invasive mosquito species to the US, and are vectors of diseases such as dengue fever, chikungunya, and Zika. These species live in heavily populated, urban areas, where they have a high accessibility to human hosts as well as to plants in backyards and town landscapes. Therefore, it is important to understand what plants may attract or repel mosquitoes to inform citizens and municipal authorities accordingly. Here, we analyzedAe. aegyptiandAe. albopictussugar-feeding behavior with eleven different commonly planted ornamental plant species. We then assessed feeding activity using the anthrone method and identified volatile composition of plant headspace using gas-chromatography mass-spectroscopy. Finally, we determined the sugar-feeding activity of field caught mosquitoes using the plant DNA barcoding technique and compared these results with the eleven ornamental species tested in the laboratory. The potential for application to disease vector control is also discussed.
Localization and function of multivesicular-bodies that release exosomes in islet cells: dysregulation during type-2 diabetes
Authors: Priyadarshini Veerabhadraswamy , Belekar Prajakta , Kothegala Lakshmi , Gandasi Nikhil R. 
Published: April 2023

AbstractType-2 diabetes (T2D) is characterized by high blood glucose due to compromised insulin secretion from pancreatic β-cells. β-cells primarily comprise insulin-secreting large-dense-core-vesicles/insulin-secretory-granules (ISGs) and also multivesicular-bodies (MVBs). MVBs are vesicles of endosomal origin containing intraluminal vesicles, which upon fusion with the plasma membrane, secrete exosomes. These play a significant role in the physiology and pathology of T2D via intercellular communication. The role of MVBs and their influence on ISGs of β-cells or their characterization is yet to be uncovered. In our study, we characterized the role of MVBs by comparing them to largely well-characterized ISGs in β-cells. We compared the density, localization, and exocytosis of MVBs with ISGs in β-cells. For this, we developed a novel probe where we exploit the efficiency of tetraspanins CD63 and CD151 to label the MVBs in β-cells. We showed that the β-cells have a significantly higher density of ISGs than MVBs. MVBs and ISGs are spatially localized apart within β-cells. The proteins that localize with MVBs are different from the ones that localize with ISGs. Exocytosis of ISGs occurs at the periphery of the β-cells and takes significantly lesser time when compared to exosome release, which is non-peripheral and takes a longer duration. Further, we also observed a significant reduction in the density of ISGs and MVBs in T2D patients’ islets compared to healthy controls. Studying the effect of MVBs on insulin secretion in physiological and T2D conditions has huge potential. This study provides a strong basis to open new avenues for such future studies.
Can ChatGPT pass Glycobiology?
Authors: Williams Devin Ormsby , Fadda Elisa 
Published: April 2023

AbstractThe release of text-generating applications based on interactive Large Language Models (LLMs) in late 2022 triggered an unprecedented and ever-growing interest worldwide. The almost instantaneous success of LLMs stimulated lively discussions in public media and in academic fora alike on the value and potentials of such tools in all areas of knowledge and information acquisition and distribution, but also about the dangers posed by their uncontrolled and indiscriminate use. This conversation is now particularly active in the higher education sector, where LLMs are seen as a potential threat to academic integrity at all levels, from facilitating cheating by students in assignments, to plagiarising academic writing in the case of researchers and administrators. Within this framework, we were interested in testing the boundaries of the LLM ChatGPT (www.openai.com) in areas of our scientific interest and expertise, and in analysing the results from different perspectives, i.e. of a final year BSc student, of a research scientist, and of a lecturer in higher education. To this end, in this paper we present and discuss a systematic evaluation on how ChatGPT addresses progressively complex scientific writing tasks and exam-type questions in Carbohydrate Chemistry and Glycobiology. The results of this project allowed us to gain insight on, 1) the strengths and limitations of the ChatGPT model to provide relevant and (most importantly) correct scientific information, 2) the format(s) and complexity of the query required to obtain the desired output, and 3) strategies to integrate LLMs in teaching and learning.
Predicting hERG repolarization power at 37°C from recordings at room temperature
Authors: Oliveira-Mendes Barbara B.R. , Alameh Malak , Montnach Jérôme , Ollivier Béatrice , Gibaud Solène , Feliciangeli Sylvain , Lesage Florian , Charpentier Flavien , Loussouarn Gildas , De Waard Michel , Baró Isabelle 
Published: April 2023

AbstractMutations in theKCNH2gene cause long or short QT syndromes (LQTS or SQTS) predisposing to life-threatening arrhythmias.KCNH2encodes for the voltage-gated K+channel hERG involved in the late repolarization phase of the cardiac action potential (AP). For the last decades, sequencingKCNH2has provided a plethora of variants associated or not with clear pathological cardiac phenotypes. Identifying pathogenic or likely pathogenic variants from the benign ones would provide useful information to clarify the genetic background of LQTS patients and relatives, and to stratify the risk of adverse events. In face of a wide spectrum of hERG biophysical defects, we looked for a way to summarize the net loss or gain of function in a unique index. In a previous work, we defined as the repolarization power the time integral of the K+currents developed during an AP clamp. Here, with the aim of accelerating the functional characterization of hERG variants using automated patch-clamp, we adapted the AP-clamp protocol to establish, at room temperature, at which the recording success rate is high, a repolarization power index, as reliable and informative as the one measured at physiological temperature. We also illustrate that the repolarization power determined at room temperature is predictive of the repolarization power at physiological temperature for 2 pathogenic hERG variants with different biophysical dysfunctions.
RBP-J regulates homeostasis and function of circulating Ly6Clomonocytes
Authors: Kou Tiantian , Kang Lan , Zhang Bin , Li Jiaqi , Zhao Baohong , Zeng Wenwen , Hu Xiaoyu 
Published: April 2023

AbstractNotch-RBP-J signaling plays an essential role in maintenance of myeloid homeostasis. However, its role in monocyte cell fate decisions is not fully understood. Here we showed that conditional deletion of transcription factor RBP-J in myeloid cells resulted in marked accumulation of blood Ly6Clomonocytes that highly expressed chemokine receptor CCR2. Bone marrow transplantation and parabiosis experiments revealed a cell intrinsic requirement of RBP-J for controlling blood Ly6CloCCR2himonocytes. RBP-J-deficient Ly6Clomonocytes exhibited enhanced capacity competing with wildtype counterparts in blood circulation. In accordance with alterations of circulating monocytes, RBP-J deficiency led to markedly increased population of lung tissues with Ly6Clomonocytes and CD16.2+interstitial macrophages. Furthermore, RBP-J deficiency-associated phenotypes could be genetically corrected by further deletingCcr2in myeloid cells. These results demonstrate that RBP-J functions as a crucial regulator of blood Ly6Clomonocytes and thus derived lung-resident myeloid populations, at least in part through regulation of CCR2.
Nanomolar interactions of alpha-synuclein fibrils to tau determined by FCS
Authors: Ramirez Jennifer , Brackhahn Emily Ann Elizabeth , Petersson E. James , Rhoades Elizabeth 
Published: April 2023

ABSTRACTAge-related neurodegenerative disorders like Alzheimer’s disease (AD) and Parkinson’s disease (PD) are characterized by deposits of protein aggregates, or amyloid, in various regions of the brain. Traditionally, aggregation of a single protein was observed to be correlated with these different pathologies: tau in AD and α-synuclein (αS) in PD. However, there is increasing evidence that the pathologies of these two diseases overlap, and the individual proteins may promote each other’s aggregation. Both tau and αS are intrinsically disordered proteins (IDPs), lacking stable secondary and tertiary structure under physiological conditions. In this study we used a combination of biochemical and biophysical techniques to interrogate the interaction of tau with both soluble and fibrillar αS. Fluorescence correlation spectroscopy (FCS) was used to assess the interactions of specific domains of fluorescently labeled tau with full length and C-terminally truncated αS in both monomeric and fibrillar forms. We found that full-length tau as well as individual tau domains interact with monomer αS weakly, but this interaction is much more pronounced with αS seeds. This interaction does not impact tau aggregation or fibril formation. These findings provide insight into the nature of interactions between tau and αS as well as the domains responsible.
Characterizing the monomer-dimer equilibrium of UbcH8/Ube2L6: A combined SAXS and NMR study
Authors: Kahraman Kerem , Robson Scott A. , Göcenler Oktay , Yenici Cansu M. , Tozkoparan Cansu D. , Klein Jennifer M. , Dötsch Volker , Elgin Emine Sonay , Haas Arthur L. , Ziarek Joshua J. , Dağ Çağdaş 
Published: April 2023

ABSTRACTInterferon-stimulated gene-15 (ISG15) is an interferon-induced protein with two ubiquitin-like (Ubl) domains linked by a short peptide chain, and the conjugated protein of the ISGylation system. Similar to ubiquitin and other Ubls, ISG15 is ligated to its target proteins through a series of E1, E2, and E3 enzymes known as Uba7, Ube2L6/UbcH8, and HERC5, respectively. Ube2L6/UbcH8 plays a literal central role in ISGylation, underscoring it as an important drug target for boosting innate antiviral immunity. Depending on the type of conjugated protein and the ultimate target protein, E2 enzymes have been shown to function as monomers, dimers, or both. UbcH8 has been crystalized in both monomeric and dimeric forms, but the functional state is unclear. Here, we used a combined approach of small-angle X-ray scattering (SAXS) and nuclear magnetic resonance (NMR) spectroscopy to characterize UbcH8’s oligomeric state in solution. SAXS revealed a dimeric UbcH8 structure that could be dissociated when fused N-terminally to glutathione S-transferase. NMR spectroscopy validated the presence of a concentration-dependent monomer-dimer equilibrium and suggested a backside dimerization interface. Chemical shift perturbation and peak intensity analysis further suggest dimer-induced conformational dynamics at E1 and E3 interfaces - providing hypotheses for the protein’s functional mechanisms. Our study highlights the power of combining NMR and SAXS techniques in providing structural information about proteins in solution.
Zn2+is Essential for Ca2+Oscillations in Mouse Eggs
Authors: Akizawa Hiroki , Lopes Emily , Fissore Rafael A. 
Published: April 2023

AbstractChanges in the intracellular concentration of free calcium (Ca2+) underpin egg activation and initiation of development in animals and plants. In mammals, the Ca2+release is periodical, known as Ca2+oscillations, and mediated by the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1). Another divalent cation, zinc (Zn2+), increases exponentially during oocyte maturation and is vital for meiotic transitions, arrests, and polyspermy prevention. It is unknown if these pivotal cations interplay during fertilization. Here, using mouse eggs, we showed that basal concentrations of labile Zn2+are indispensable for sperm-initiated Ca2+oscillations because Zn2+-deficient conditions induced by cell-permeable chelators abrogated Ca2+responses evoked by fertilization and other physiological and pharmacological agonists. We also found that chemically- or genetically generated eggs with lower levels of labile Zn2+displayed reduced IP3R1 sensitivity and diminished ER Ca2+leak despite the stable content of the stores and IP3R1 mass. Resupplying Zn2+restarted Ca2+oscillations, but excessive Zn2+prevented and terminated them, hindering IP3R1 responsiveness. The findings suggest that a window of Zn2+concentrations is required for Ca2+responses and IP3R1 function in eggs, ensuring optimal response to fertilization and egg activation.