bluuebunny/crossref_metadata_2025_split huggingface dataset:
LSM14B is essential for mitochondrial clustering in the oocyte meiosis
Authors: Wan Yanling , Yang Shuang , Li Tongtong , Cai Yuling , Zhang Mingyu , Huang Tao , Lv Yue , lu Gang , Li Jingxin , Sha Qianqian , Chen Zijiang , Liu Hongbin 
Published: April 2023

AbstractAs oocyte meiotic maturation, they undergo two successive meiotic M phases, notably lacking an intervening interphase phase. During these M phases, oocytes remain transcriptionally quiescent, and we now know that “translational repressed mRNAs” are stored in a structure called the mitochondria associated ribonucleoprotein domain (MARDO). LSM14B is one of the abundant proteins of MARDO, and is predicted to bind mRNA, but its function(s) remain elusive. Here, we demonstrate that LSM14B functions to promote MARDO assembly in mouse oocytes. We also found that LSM14B knockout female mice are infertile, and show that the knockout oocytes fail to enter meiosis II, instead entering an aberrant interphase-like stage. Finally, we show that the failure of oocyte maturation results from decreased expression of Cyclin B1. Our study has revealed that the RNA-binding protein LSM14B modulates MARDO assembly and is essential for oocyte meiotic maturation.
Unveiling dynamics behind Glioblastoma Multiforme single-cell data heterogeneity
Authors: Vieira Junior Marcos Guilherme , de Almeida Côrtes Adriano Maurício , Gonçalves Carneiro Flávia Raquel , Carels Nicolas , da Silva Fabrício Alves Barbosa 
Published: April 2023

AbstractGlioblastoma Multiforme (GBM), a brain tumor distinguished for its aggressive nature, presents heterogeneity that stems from multifaceted mechanisms, such as genetic mutations, epigenetic modifications, genomic instability, and selective pressures. We reason that the aggressiveness of GBM enables even a limited dataset to serve as a representative sample within the domain of cancer attractors, allowing our sample to reflect a representative trajectory within the attractor’s domain. Utilizing single-cell RNA sequencing data, we proceed with a detailed analysis of GBM’s cellular landscape. Rooted in characteristics observed in stochastic systems, we considered factors like genomic instability to introduce a level of noise or unpredictability, thereby characterizing the cancer dynamics through stochastic fixed points. These fixed points, derived from centroids obtained through various clustering methods, were rigorously verified for method sensitivity. This methodological foundation, wherein sample and time averages are equivalent, assigns paramount interpretative value to the data cluster centroids, aiding both in parameter fitting and subsequent stochastic simulations. This scenario is supported by the compelling correlation found between centroids of experimental and simulated datasets. The use of stochastic modeling to compute the Waddington landscape enriched our analysis of GBM’s cellular heterogeneity and provided a visual framework for validating the centroids and standard deviations as accurate characterizations of potential cancer attractors. Specifically, this approach allowed us to assess the compatibility between data dispersion and the corresponding basin of attraction, thereby bridging molecular-level variations and systems-level dynamics. We also examined the stability and transitions between these attractors, revealing a potential interplay between subtypes and potentially uncovering factors that drive cancer recurrence and progression. By connecting molecular mechanisms related to cancer heterogeneity with statistical properties of gene expression dynamics we expect to set the stage for the development of potential diagnostic tools and pave the way for personalized therapeutic interventions.
Receptor-like cytoplasmic kinases belonging to different subfamilies mediate immune responses downstream of the Cf-4 resistance protein inNicotiana benthamiana
Authors: Huang Wen R.H. , Braam Ciska , Kretschmer Carola , Liu Huan , Ferik Filiz , van der Burgh Aranka M. , Pluis Max , Hagan Agnes Omabour , Villanueva Sergio Landeo , Wu Jinbin , Loosbroek Amber van , Wang Yulu , Seidl Michael F. , Stuttmann Johannes , Joosten Matthieu H.A.J. 
Published: April 2023

ABSTRACTCell-surface receptors, which are either receptor-like proteins (RLPs) or receptor-like kinases (RLKs), form the first layer of the plant innate immune system. The LRR-RLKs SUPPRESSOR OF BIR1-1 (SOBIR1) and BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1) are the common regulatory co-receptors of LRR-RLPs. The tomato LRR-RLP Cf-4, which specifically detects the apoplastic effector Avr4 that is secreted by the pathogenic intercellular fungusCladosporium fulvum, requires SOBIR1 and BAK1 to mediate resistance against this fungus. It is proposed that phosphorylation events take place between the cytoplasmic kinase domains of SOBIR1 and BAK1, which lead to the initiation of various downstream signaling outputs such as the rapid phosphorylation of receptor-like cytoplasmic kinases (RLCKs), the accumulation of reactive oxygen species (ROS), the activation of mitogen-activated protein kinase (MAPK) cascades, and in some cases, the hypersensitive response (HR). Here, by performingin vitrophosphorylation assays, we show that SOBIR1 directly phosphorylates BAK1, whereas BAK1, in its turn, directly phosphorylates SOBIR1, which results in the full activation of the Cf-4-containing immune complex. We found that threonine 522, present in the activation segment of the SOBIR1 kinase domain ofNicotiana benthamiana(Nb), is required for its intrinsic kinase activity, and is essential for the Avr4/Cf-4/SOBIR1/BAK1-triggered ROS burst, MAPK activation and the HR. Tyrosine residue Y469 was found to be crucial for the Avr4/Cf-4- triggered activation of MAPKs and the HR, but not for ROS production andNbSOBIR1 intrinsic kinase activity. RLCKs are well-recognized to act as the initial cytoplasmic transducers, bridging cell-surface receptor complexes with their downstream signaling partners. By knocking out multiple genes belonging to different RLCK-VII subfamilies inN. benthamianaplants stably expressingCf-4, we show that members of the RLCK-VII subfamilies 6, 7 and 8 are required for the Avr4/Cf-4-triggered ROS production. Typically, the Avr4 protein triggers a biphasic ROS burst in leaf discs obtained fromN. benthamiana:Cf-4plants, in which the first transitory response is followed by a second, sustained ROS burst. Interestingly, the intensities of the first and second phase of the ROS burst are affected in different ways in the variousrlck-viiknock-out plants, indicating that there are different downstream ROS regulatory mechanisms, involving different RLCKs inN. benthamiana. Further studies show that members from RLCK-VII-6, 7 and 8 also play an essential role in regulating the ROS production triggered by flg22, chitin, and the nlp20/RLP23 and the pg13/RLP42 combinations.
Raynals, an online tool for the analysis of dynamic light scattering
Authors: Burastero Osvaldo , Draper-Barr George , Raynal Bertrand , Chevreuil Maelenn , England Patrick , Garcia-Alai Maria M. 
Published: April 2023

AbstractDynamic light scattering (DLS) is routinely employed to assess the homogeneity and size distribution profile of samples containing microscopic particles in suspension or solubilised polymers. In this work, we introduce Raynals, an user-friendly software for the analysis of single-angle DLS data that uses the Tikhonov-Phillips regularisation. Performance is evaluated on simulated and experimental data, generated by different DLS instruments, for several proteins and gold nanoparticles. DLS data can be easily misinterpreted and the simulation tools available in Raynals allow understanding of the limitations of the measurement and its resolution. It has been designed as a tool to address quality control of biological samples, during sample preparation and optimisation, and it helps in the detection of aggregates showing the influence of large particles. Last, Raynals provides flexibility in the way the data is presented, allows exporting publication-quality figures, it is free for academic use, and can be accessed online on the eSPC data analysis platform at spc.embl-hamburg.de.
The Calcium Transient Coupled to the L-Type Calcium Current Attenuates Action Potential Alternans
Authors: Warren Mark , Poelzing Steven 
Published: April 2023

AbstractBackgroundAction potential (AP) alternans are linked to increased arrhythmogenesis. It is suggested that calcium (Ca2+) transient (CaT) alternans cause AP alternans through bi-directional coupling feedback mechanisms because CaT alternans can precede AP alternans and develop in AP alternans free conditions. However, the CaT is an emergent response to intracellular Ca2+handling, and the mechanisms linking AP and CaT alternans are still a topic of investigation. This study investigated the development of AP alternans in the absence of CaT.MethodsAP (patch clamp) and intracellular Ca2+(Fluo-4 epifluorescence) were recorded simultaneously from isolated rabbit ventricle myocytes perfused with the intracellular Ca2+buffer BAPTA (10-20 mM) to abolish CaT and/or the L-type Ca2+ channel activator Bay K 8644 (25 nM).ResultsAfter a rate change, alternans were critically damped and stable, overdamped and ceased over seconds, underdamped with longer scale harmonics, or unstably underdamped progressing to 2:1 capture. Alternans in control cells were predominantly critically damped, but after CaT ablation with 10 or 20 mM BAPTA, exhibited respectively increased overdamping or increased underdamping. Alternans were easier to induce in CaT free cells as evidenced by a higher alternans threshold (ALT-TH: at least 7 pairs of alternating beats) relative to control cells. Alternans in Bay K 8644 treated cells were often underdamped, but the ALT-TH was similar to control. In CaT ablated cells, Bay K 8644 prolonged AP duration (APD) leading predominantly to unstably underdamped alternans.ConclusionsAP alternans occur more readily in the absence of CaT suggesting that the CaT dampens the development of AP alternans. The data further demonstrate that agonizing the L-type calcium current without the negative feedback of the CaT leads to unstable alternans. This negative feedback mechanism may be important for understanding treatments aimed at reducing CaT or its dynamic response to prevent arrhythmias.
Endothelial structure contributes to heterogeneity in brain capillary diameter
Authors: Sargent Sheridan M. , Bonney Stephanie K. , Li Yuandong , Stamenkovic Stefan , Takeno Marc , Coelho-Santos Vanessa , Shih Andy Y. 
Published: April 2023

ABSTRACTThe high metabolic demand of brain tissue is supported by a constant supply of blood through dense microvascular networks. Capillaries are the smallest class of vessels and vary in diameter between ∼2 to 5 μm in the brain. This diameter range plays a significant role in the optimization of blood flow resistance, blood cell distribution, and oxygen extraction. The control of capillary diameter has largely been ascribed to pericyte contractility, but it remains unclear if endothelial wall architecture also contributes to capillary diameter heterogeneity. Here, we use public, large-scale volume electron microscopy data from mouse cortex (MICrONS Explorer, Cortical MM^3) to examine how endothelial cell number, endothelial cell thickness, and pericyte coverage relates to microvascular lumen size. We find that transitional vessels near the penetrating arteriole and ascending venule are composed of 2 to 5 interlocked endothelial cells, while the numerous capillary segments intervening these zones are composed of either 1 or 2 endothelial cells, with roughly equal proportions. The luminal area and diameter is on average slightly larger with capillary segments composed of 2 interlocked endothelial cells versus 1 endothelial cell. However, this difference is insufficient to explain the full range of capillary diameters seen in vivo. This suggests that both endothelial structure and other influences, such as pericyte tone, contribute to the basal diameter and optimized perfusion of brain capillaries.
Nitric oxide suppresses cilia activity in ctenophores
Authors: Norekian Tigran P. , Moroz Leonid L. 
Published: April 2023

AbstractCilia are the major effectors in Ctenophores, but very little is known about their transmitter control and integration. Here, we present a simple protocol to monitor and quantify cilia activity in semi-intact preparations and provide evidence for polysynaptic control of cilia coordination in ctenophores. Next, we screen the effects of several classical bilaterian neurotransmitters (acetylcholine, dopamine, L-DOPA, serotonin, octopamine, histamine, gamma-aminobutyric acid (GABA), L-aspartate, L-glutamate, glycine), neuropeptides (FMRFamide), and nitric oxide (NO) on cilia beating inPleurobrachia bacheiandBolinopsis infundibulum. Only NO inhibited cilia beating, whereas other tested transmitters were ineffective. These findings further suggest that ctenophore-specific neuropeptides could be major candidate signaling molecules controlling cilia activity in representatives of this early-branching metazoan lineage.
Temperature and turbidity interact synergistically to alter anti-predator behaviour in the Trinidadian guppy
Authors: Zanghi Costanza , Munro Milly , Ioannou Christos C 
Published: April 2023

AbstractDue to climate change, freshwater habitats are facing increasing temperatures and more extreme weather that disrupts water flow. Together with eutrophication and sedimentation from farming, quarrying and urbanisation, freshwaters are becoming more turbid as well as warmer. Predators and prey need to be able to respond to one another adaptively, yet how changes in temperature and turbidity interact to affect predator-prey behaviour remains unexplored. Using a fully factorial design, we tested the combined effects of increased temperature and turbidity on the behaviour of guppy shoals (Poecilia reticulata) in the presence of one of their natural cichlid predators, the blue acara (Andinoacara pulcher). Our results demonstrate that the prey and predator were in closest proximity in warmer, turbid water, with an interaction between these stressors showing a greater than additive effect. There was also an interaction between the stressors in the inter-individual distances between the prey, where shoal cohesion increased with temperature in clear water, but decreased when temperature increased in turbid water. The closer proximity to predators and reduction in shoaling in turbid, warmer water may increase the risk of predation for the guppy, suggesting that the combined effects of elevated temperature and turbidity may favour predators rather than prey.
Task-relevant object shape properties act as poor but viable cues for the attribution of motor errors to external objects
Authors: Modchalingam Shanaathanan , Ayala Maria N. , Henriques Denise Y. P. 
Published: April 2023

ABSTRACTWhen a context change is detected during motor learning, motor memories - internal models for executing movements within some context - may be created or existing motor memories may be activated and modified. Assigning credit to plausible causes of errors can allow for fast retrieval and activation of a motor memory, or a combination of motor memories, when the presence of such causes is detected. Features of the movement-context intrinsic to the movement dynamics, such as posture of the end effector, are often effective cues for detecting context change whereas features extrinsic to the movement dynamics, such as the colour of an object being moved, are often not. These extrinsic cues are typically not relevant to the motor task at hand and can be safely ignored by the motor system. We conducted two experiments testing if extrinsic but task-relevant object-shape cues during an object- transport task can act as viable contextual cues for error assignment to the object, and the creation of new, object-shape-associated motor memories. In the first experiment we find that despite the object- shape cues, errors are primarily attributed to the hand transporting the object. In a second experiment, we find that although participants can execute differing movements cued by the object shape in a dual adaptation task, they primarily use explicit strategies to do so.
Discovery of GS-5245 (Obeldesivir), an Oral Prodrug of Nucleoside GS-441524 that Exhibits Antiviral Efficacy in SARS-CoV-2 Infected African Green Monkeys
Authors: Mackman Richard L. , Kalla Rao , Babusis Darius , Pitts Jared , Barrett Kimberly T. , Chun Kwon , Du Pont Venice , Rodriguez Lauren , Moshiri Jasmine , Xu Yili , Lee Michael , Lee Gary , Bleier Blake , Nguyen Anh-Quan , O’Keefe B. Michael , Ambrosi Andrea , Cook Meredith , Yu Joy , Dempah Elodie , Bunyan Elaine , Riola Nicholas C. , Lu Xianghan , Liu Renmeng , Davie Ashley , Hsiang Tien-Ying , Gale Michael , Niedziela-Majka Anita , Feng Joy Y. , Hedskog Charlotte , Bilello John P. , Subramanian Raju , Cihlar Tomas 
Published: April 2023

AbstractRemdesivir1is an amidate prodrug that releases the monophosphate of nucleoside GS-441524 (2) into lung cells thereby forming the bioactive triphosphate2-NTP.2-NTP, an analog of ATP, inhibits the SARS-CoV-2 RNA-dependent RNA polymerase replication and transcription of viral RNA. Strong clinical results for1have prompted interest in oral approaches to generate2-NTP. Here we describe the discovery of a 5’-isobutyryl ester prodrug of2 (GS-5245, Obeldesivir,3) that has low cellular cytotoxicity and three to seven-fold improved oral delivery of2in monkeys. Prodrug3is cleaved pre-systemically to provide high systemic exposures of2that overcome its less efficient metabolism to2-NTPleading to strong SARS-CoV-2 antiviral efficacy in an African green monkey infection model. Exposure-based SARS-CoV-2 efficacy relationships resulted in an estimated clinical dose of 350-400 mg twice-daily. Importantly, all SARS-CoV-2 variants remain susceptible to2which supports development of3as a promising COVID-19 treatment.
The emergence of digital learning in higher education: a lesson from the COVID-19 pandemic
Authors: Al Masud Abdullah , Hossain Md. Alamgir , Biswas Sukanta , Ruma Afroza Parvin , Rahman Kazi Shoyebur , Tagore Saurabh 
Published: April 2023

PurposeThe coronavirus disease 2019 (COVID-19) has a significant influence on many aspects of life, including education. As a result, the education system in emerging nations such as Bangladesh needs a rapid transition from conventional to technology-based distance learning. This study looks at the current state of higher education and how well online courses that use technology work.Design/methodology/approachThis study used a structural equation model (SEM) to analyze the 392 student records taken from several universities in Bangladesh.FindingsThis research showed that students are more likely to use a digital higher education system if faculty are willing, students are eager and the economy is stable. Students who have had a bad experience with digital learning should know that a virtual evaluation system is needed. The willingness of students to use technology also plays a significant role in whether or not the students will take online classes. The research shows that combining traditional classroom and online learning is the best way to create a long-term learning system.Originality/valueThe model suggested in this study has a big effect, and Bangladesh policymakers should consider this model when planning a new kind of technology-based education.
Ownership structure and firm sustainable investments: evidence from emerging markets
Authors: Qasem Ameen , Mohammed Abdulalem , Battisti Enrico , Ferraris Alberto 
Published: April 2023

PurposeThe aim of this study is to examine the ownership impact on firm sustainable investments (FSIs). In particular, this research examines the link between institutional investor ownership (IIO), managerial ownership (MOWN) and FSIs in the tourism industry in Malaysia.Design/methodology/approachThis study uses a data set of 346 firm-year observations from 2008 to 2020 and applies feasible generalized least squares (FGLS) regression analysis. The study sample is based on tourism firms listed on Bursa Malaysia (the Malaysian Stock Exchange).FindingsThere is a significant positive association between IIO and FSIs. When IIO is classified into foreign (FIIO) and local (LIIO), this significant association is mainly driven by FIIO. In addition, there is a significant, positive association between managerial ownership (MOWN) and firm sustainable investments (FSIs). These findings imply that firm ownership has an influence on FSIs in the tourism industry.Originality/valueThis is the first attempt to consider IIO and MOWN simultaneously in a single model estimation. The findings contribute to emerging capital markets where the involvement of ownership concentration in the governance of publicly listed firms is a common practice.
Dialect connectedness and tunneling: evidence from China
Authors: Song Chen 
Published: April 2023

PurposeThis study aims to examine the effects of dialect connectedness between the chairman and the chief executive officer (CEO) (DCCC) on the tunneling activities of controlling shareholders.Design/methodology/approachThis study uses abnormal related-party transactions (ARPT) as a proxy for tunneling activities and traces dialects of chairmen and CEOs based on the respective birthplace information. Baseline results are examined using a fixed-effects model. The results remain robust when using the instrumental variable approach, propensity score matching (PSM) technique, changing the measurement of tunneling and Heckman two-step selection model.FindingsThe results show that DCCC reduces tunneling activities. This negative association is more pronounced for non-state-owned enterprises and firms whose chairmen and CEOs work in the respective hometowns. DCCC restrains tunneling activities through mechanisms by establishing an informal supervisory effect on CEOs because the CEOs fear reputational damage and strengthening cooperation between chairmen and CEOs. Further analyses suggest that this negative association is more significant when chairmen and CEOs are non-controlling shareholders, but the association is weakened during the coronavirus disease 2019 (COVID-19) crisis.Originality/valueAs dialect is a carrier of culture, this study's results imply that cultural proximity can replace formal mechanisms to enhance corporate governance.