bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local field potential sharp waves with diversified impact on cortical neuronal encoding of haptic input
Authors: Kristensen Sofie S. , Jörntell Henrik 
Published: November 2023

AbstractCortical sensory processing is greatly impacted by internally generated activity. But controlling for that activity is difficult since the thalamocortical network is a high-dimensional system with rapid state changes. Therefore, to unwind the cortical computational architecture there is a need for physiological ‘landmarks’ that can be used as frames of reference for computational state. Here we use a waveshape transform method to identify conspicuous local field potential sharp waves (LFP-SPWs) in the somatosensory cortex (S1). LFP-SPW events triggered short-lasting but massive neuronal activation in all recorded neurons with a subset of neurons initiating their activation up to 20 ms before the LFP-SPW onset. In contrast, LFP-SPWs differentially impacted the neuronal spike responses to ensuing tactile inputs, depressing the tactile responses in some neurons and enhancing them in others. When LFP-SPWs coactivated with more distant ECoG-SPWs, suggesting an involvement of these SPWs in global cortical signaling, the impact of the LFP-SPW on the neuronal tactile response could change substantially, including inverting its impact to the opposite. These cortical SPWs had similar overall activity patterns as reported for hippocampal SPWs and may be a biomarker for a particular type of state change that possibly involves both hippocampus and neocortex.
Proteome-wide base editor screens to assess phosphorylation site functionality in high-throughput
Authors: Kennedy Patrick H , Deh Sheikh Amin Alborzian , Balakar Matthew , Jones Alexander C , Olive Meagan E , Hegde Mudra , Matias Maria I , Pirete Natan , Burt Rajan , Levy Jonathan , Little Tamia , Hogan Patrick G , Liu David R , Doench John G , Newton Alexandra C , Gottschalk Rachel A. , de Boer Carl , Alarcón Suzie , Newby Gregory , Myers Samuel A. 
Published: November 2023

AbstractSignaling pathways that drive gene expression are typically depicted as having a dozen or so landmark phosphorylation and transcriptional events. In reality, thousands of dynamic post-translational modifications (PTMs) orchestrate nearly every cellular function, and we lack technologies to find causal links between these vast biochemical pathways and genetic circuits at scale. Here, we describe “signaling-to-transcription network” mapping through the development of PTM-centric base editing coupled to phenotypic screens, directed by temporally-resolved phosphoproteomics. Using T cell activation as a model, we observe hundreds of unstudied phosphorylation sites that modulate NFAT transcriptional activity. We identify the phosphorylation-mediated nuclear localization of the phosphatase PHLPP1 which promotes NFAT but inhibits NFκB activity. We also find that specific phosphosite mutants can alter gene expression in subtle yet distinct patterns, demonstrating the potential for fine-tuning transcriptional responses. Overall, base editor screening of PTM sites provides a powerful platform to dissect PTM function within signaling pathways.
Impulse initiation in engrafted pluripotent stem cell-derived cardiomyocytes can stimulate the recipient heart
Authors: Stüdemann Tim , Schwarzova Barbora , Schneidewind Till , Geertz Birgit , von Bibra Constantin , Nehring Marie , Rössinger Judith , Wiegert J. Simon , Eschenhagen Thomas , Weinberger Florian 
Published: November 2023

AbstractTransplantation of pluripotent stem cell-derived cardiomyocytes is a novel promising cell-based therapeutic approach for patients with heart failure. However, engraftment arrhythmias are a predictable life-threatening complication and represent a major hurdle for clinical translation. Catheter-based electrophysiological analysis suggested that the ventricular arrhythmias were caused by an automaticity of the transplanted cells, but whether impulse generation by transplanted cardiomyocytes can propagate to the host myocardium and override the recipient rhythm has not been directly assessed experimentally. We used optogenetics to specifically activate engrafted cardiomyocytes, which resulted in impulse generation in the engrafted cardiomyocytes and stimulated the recipient heart (4/9 hearts). Thus, our study shows that transplanted cardiomyocytes can electrically couple to the host myocardium and stimulate the recipient heart, providing experimental evidence that cardiomyocyte automaticity can serve as a trigger for ventricular arrhythmias.
From Data to Insights: Machine Learning Empowers Prognostic Biomarker Prediction in Autism
Authors: Mehmetbeyoglu Ecmel , Duman Abdulkerim , Taheri Serpil , Ozkul Yusuf , Rassaulzadegan Minoo 
Published: November 2023

AbstractAutism Spectrum Disorder (ASD) poses significant challenges to society and science due to its impact on communication, social interaction, and repetitive behaviour patterns in affected children. The Autism and Developmental Disabilities Monitoring (ADDM) Network continuously monitors ASD prevalence and characteristics. In 2020, ASD prevalence was estimated at one in 36 children, with higher rates than previous estimates. This study focuses on ongoing ASD research conducted by Erciyes University. Serum samples from 45 ASD patients and 21 unrelated control participants were analysed to assess the expression of 372 microRNAs (miRNAs). Six miRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) exhibited significant downregulation in all ASD patients compared to healthy controls. The current study endeavours to identify dependable diagnostic biomarkers for ASD, addressing the pressing need for non-invasive, accurate, and cost-effective diagnostic tools, as current methods are subjective and time intensive. A pivotal discovery in this study is the potential diagnostic value of miR-126-3p, offering the promise of earlier and more accurate ASD diagnoses, potentially leading to improved intervention outcomes. Leveraging machine learning, such as the K-nearest neighbours (KNN) model, presents a promising avenue for precise ASD diagnosis using miRNA biomarkers.
Rapid meiotic prophase chromosome movements inArabidopsis thalianaare linked to essential reorganization at the nuclear envelope
Authors: Cromer Laurence , Tiscareno-Andrade Mariana , Lefranc Sandrine , Chambon Aurélie , Hurel Aurélie , Brogniez Manon , Guérin Julie , Masson Ivan Le , Adam Gabrielle , Charif Delphine , Andrey Philippe , Grelon Mathilde 
Published: November 2023

AbstractMeiotic rapid prophase chromosome movements (RPMs) require connections between the chromosomes and the cytoskeleton, involving SUN (Sad1/UNC-84)-domain-containing proteins at the inner nuclear envelope (NE). RPMs remain significantly understudied in plants, notably with respect to their importance in the regulation of meiosis. Here, we demonstrate thatArabidopsis thalianameiotic centromeres undergo rapid (up to 500 nm/s) and uncoordinated movements during the zygotene and pachytene stages. RPMs are not affected by altered chromosome organization and recombination but are abolished in the double mutantsun1 sun2. We also document the changes in chromosome dynamics and nucleus organization during the transition from leptotene to zygotene, including telomere attachment to SUN-enriched NE domains, bouquet formation, and nucleolus displacement, all of which were defective insun1 sun2. These results establishA. thalianaas a new model species for studying the functional implications of meiotic RPMs and demonstrate the mechanistic conservation of telomere-led RPMs in plants.
Non-synaptic plasticity enables memory-dependent local learning
Authors: Romain Ferrand , Maximilian Baronig , Florian Unger , Robert Legenstein 
Published: November 2023

AbstractSynaptic plasticity is essential for memory formation and learning in the brain. In addition, recent results indicate that non-synaptic plasticity processes such as the regulation of neural membrane properties contribute to memory formation, its functional role in memory and learning has however remained elusive. Here, we propose that non-synaptic and synaptic plasticity are both essential components to enable memory-dependent processing in neuronal networks. While the former acts on a fast time scale for rapid information storage, the latter shapes network processing on a slower time scale to harness this memory as a functional component. We analyse this concept in a network model where pyramidal neurons regulate their apical trunk excitability in a Hebbian manner. We find that local synaptic plasticity rules can be derived for this model and show that the interplay between this synaptic plasticity and the non-synaptic trunk plasticity enables the model to successfully accommodate memory-dependent processing capabilities in a number of tasks, ranging from simple memory tests to question answering. The model can also explain contextual fear conditioning experiments, where freezing responses could be recovered by optogenetic reactivation of memory engrams under amnesia.Author summaryHow memory is organized in the brain in order to enable cognitive processing is a central open question in systems neuroscience. Traditionally, synaptic plasticity is considered the key mechanism for the establishment of memory in the brain. Recently however, this view has been questioned, and it was proposed that non-synaptic plasticity mechanisms play a more prominent role as previously considered. In this article, we propose that both, synaptic and non-synaptic plasticity are central components for the formation and utilization of memory in biological neuronal networks. Our results show that non-synaptic plasticity can act on a fast time-scale to store important information, while synaptic plasticity can adapt network function on a slow time scale in order to facilitate memory-dependent cognitive processing.
The development of the adult nervous system in the annelidOwenia fusiformis
Authors: Carrillo-Baltodano Allan M. , Donnellan Rory , Williams Elizabeth A. , Jékely Gáspar , Martín-Durán José M. 
Published: November 2023

AbstractBackgroundThe evolutionary origins of animal nervous systems remain contentious because we still have a limited understanding of neural development in most major animal clades. Annelids — a species-rich group with centralised nervous systems — have played central roles in hypotheses about the origins of animal nervous systems. However, most studies have focused on adults of deeply nested species in the annelid tree. Recently,Owenia fusiformishas emerged as an informative species to reconstruct ancestral traits in Annelida, given its phylogenetic position within the sister clade to all remaining annelids.MethodsCombining immunohistochemistry of the conserved neuropeptides FVamide-lir, RYamide-lir, RGWamide-lir and MIP-lir with gene expression, we comprehensively characterise neural development from larva to adulthood inOwenia fusiformis.ResultsThe early larval nervous system comprises a neuropeptide-rich apical organ connected through peripheral nerves to a prototroch ring and the chaetal sac. There are seven sensory neurons in the prototroch. A bilobed brain forms below the apical organ and connects to the ventral nerve cord of the developing juvenile. During metamorphosis, the brain compresses, becoming ring-shaped, and the trunk nervous system develops several longitudinal cords and segmented lateral nerves.ConclusionsOur findings reveal the formation and reorganisation of the nervous system during the life cycle ofO. fusiformis, an early-branching annelid. Despite its apparent neuroanatomical simplicity, this species has a diverse peptidergic nervous system, exhibiting morphological similarities with other annelids, particularly at the larval stages. Our work supports the importance of neuropeptides in animal nervous systems and the evolution of biphasic life cycles.
Acentric chromosome congression and alignment on the metaphase plate via kinetochore-independent forces inDrosophila
Authors: Vicars Hannah , Karg Travis , Mills Alison , Sullivan William 
Published: November 2023

AbstractChromosome congression and alignment on the metaphase plate involves lateral and microtubule plus-end interactions with the kinetochore. Here we take advantage of our ability to efficiently generate a GFP-marked acentric X chromosome fragment inDrosophilaneuroblasts to identify forces acting on chromosome arms that drive congression and alignment. We find acentrics efficiently align on the metaphase plate, often more rapidly than kinetochore-bearing chromosomes. Unlike intact chromosomes, the paired sister acentrics oscillate as they move to and reside on the metaphase plate in a plane distinct and significantly further from the main mass of intact chromosomes. Consequently, at anaphase onset acentrics are oriented either parallel or perpendicular to the spindle. Parallel-oriented sisters separate by sliding while those oriented perpendicularly separate via unzipping. This oscillation, together with the fact that in monopolar spindles acentrics are rapidly shunted away from the poles, indicates that distributed plus-end directed forces are primarily responsible for acentric migration. This conclusion is supported by the observation that reduction of EB1 preferentially disrupts acentric alignment. In addition, reduction of Klp3a activity, a gene required for the establishment of pole-to-pole microtubules, preferentially disrupts acentric alignment. Taken together these studies suggest that plus-end forces mediated by the outer pole-to-pole microtubules are primarily responsible for acentric metaphase alignment. Surprisingly, we find that a small fraction of sister acentrics are anti-parallel aligned indicating that the kinetochore is required to ensure parallel alignment of sister chromatids. Finally, we find induction of acentric chromosome fragments results in a global reorganization of the congressed chromosomes into a torus configuration.Article SummaryThe kinetochore serves as a site for attaching microtubules and allows for successful alignment, separation, and segregation of replicated sister chromosomes during cell division. However, previous studies have revealed that sister chromosomes without kinetochores (acentrics) often align to the metaphase plate, undergo separation and segregation, and are properly transmitted to daughter cells. In this study, we discuss the forces acting on chromosomes, independent of the kinetochore, underlying their successful alignment in early mitosis.
Targeted Metagenomic Databases Provide Improved Analysis of Microbiota Samples
Authors: Baud Agnes , Kennedy Sean P 
Published: November 2023

AbstractWe introduceMoonbase, a flexible pipeline that can be used to build targeted, project-specific, databases in order to improve the accuracy of taxonomic detection and quantification in complex microbial communities.Moonbasewas evaluated using synthetic metagenomic samples and compared against existing methods including MetaPhlAn3 and generalized Kraken2 databases. Our results indicate thatMoonbasesignificantly improves species precision and quantification, outperforming marker genes and generalized databases. Construction of a phylogenetic tree from 16S data of genomes inMoonbaseallows for the incorporation of UniFrac-type phylogenetic information into diversity calculations of samples. We demonstrate the resulting analysis has increased statistical power in distinguishing microbial communities. This study highlights the continual evolution of metagenomic tools with the goal of improving metagenomic analysis and highlights the potential of theMoonbasepipeline.
RFX6haploinsufficiency predisposes to diabetes through impaired beta cell functionality
Authors: Ibrahim Hazem , Balboa Diego , Saarimäki-Vire Jonna , Montaser Hossam , Dyachok Oleg , Lund Per-Eric , Omar-Hmeadi Muhmmad , Kvist Jouni , Dwivedi Om Prakash , Lithovius Väinö , Barsby Tom , Chandra Vikash , Eurola Solja , Ustinov Jarkko , Tuomi Tiinamaija , Miettinen Päivi J. , Barg Sebastian , Tengholm Anders , Otonkoski Timo 
Published: November 2023

AbstractRegulatory factor X 6 (RFX6) is indispensable for pancreatic endocrine development and differentiation. The RFX6 protein-truncating variant p.His293LeufsTer7 is significantly enriched in the Finnish population with almost 1:250 individuals as a carrier. Importantly, the FinnGen study indicates a high predisposition for heterozygous carriers to develop type 2 diabetes (T2D) and gestational diabetes. To understand the role of this variant in β-cell development and function, we generated allelic series of isogenic pluripotent stem cell models and directed them into pancreatic islet lineages (SC-islets). Expectedly,in-vitromodels of the homozygousRFX6−/−variant failed to generate pancreatic endocrine cells, recapitulating the phenotype in Mitchell-Riley syndrome. Notably, heterozygousRFX6+/−derived SC-islets showed reduced β-cell maturation markers and calcium oscillations, resulting in defective insulin secretion, without affecting β-cell number or insulin content. The reduced insulin secretion is sustained duringin-vivoimplantation studies, consistent with the susceptibility of the carriers to develop diabetes.TeaserModelingRFX6-assocciated neonatal and type-2 diabetes using allelic series stem cell-derived isletsin-vitroandin-vivo.
Comeback or evolution? Examining organizational resilience literature in pre and during COVID-19
Authors: Paeffgen Thea , Lehmann Tine , Feseker Mareike 
Published: November 2023

PurposeThe ability of companies to develop organizational resilience before, during and after crises is crucial for their development and growth. The future forecasts increasingly more crises, thus this paper aims at identifying key topics around organizational resilience in COVID-19 times, differentiating them of pre-crisis literature and synthesizing them into a research framework.Design/methodology/approachBased on Web of Science and Scopus, the authors analysed the content of the only twenty-seven VHB-ranked primary studies discussing organizational resilience during COVID-19, providing a complete survey of this research area.FindingsFollowing a content analysis, the authors identified main topics of interest for researchers at the moment of COVID-19, how it differed from before this adversity and provide an outlook on future research. The results presented include in the COVID-19 context: an adapted definition of organizational resilience, key theoretical framework, insights for future research. Some topics have been found to be increasingly more important during COVID-19 (i.e. digitalization, partnerships and learning) while others have been less explored although present in pre-COVID-19 research on organizational resilience (i.e. dynamic capabilities, anticipation and preparedness).Originality/valueUnderstanding key issues in global disruptions could help practitioners in fostering resilience as much as researchers in identifying new ways to advance and maintain resilience. This paper differs from other reviews by providing a full text analysis, based on qualitative content analysis, of all ranked published papers in the considered period.
Voronoi discretization to improve the meshless local Petrov–Galerkin method in 3D-computational fracture mechanics
Authors: Ariannezhad Behrooz , Shahrooi Shahram , Shishesaz Mohammad 
Published: November 2023

Purpose1) The OE-MLPG penalty meshfree method is developed to solve cracked structure.(2) Smartening the numerical meshfree method by combining the particle swarm optimization (PSO) optimization algorithms and Voronoi computational geometric algorithm. (3). Selection of base functions, finding optimal penalty factor and distribution of appropriate nodal points to the accuracy of calculation in the meshless local Petrov–Galekrin (MLPG) meshless method.Design/methodology/approachUsing appropriate shape functions and distribution of nodal points in local domains and sub-domains and choosing an approximation or interpolation method has an effective role in the application of meshless methods for the analysis of computational fracture mechanics problems, especially problems with geometric discontinuity and cracks. In this research, computational geometry technique, based on the Voronoi diagram (VD) and Delaunay triangulation and PSO algorithm, are used to distribute nodal points in the sub-domain of analysis (crack line and around it on the crack plane).FindingsBy doing this process, the problems caused by too closeness of nodal points in computationally sensitive areas that exist in general methods of nodal point distribution are also solved. Comparing the effect of the number of sentences of basic functions and their order in the definition of shape functions, performing the mono-objective PSO algorithm to find the penalty factor, the coefficient, convergence, arrangement of nodal points during the three stages of VD implementation and the accuracy of the answers found indicates, the efficiency of V-E-MLPG method with Ns = 7 and ß = 0.0037–0.0075 to estimation of 3D-stress intensity factors (3D-SIFs) in computational fracture mechanics.Originality/valueThe present manuscript is a continuation of the studies (Ref. [33]) carried out by the authors, about; feasibility assessment, improvement and solution of challenges, introduction of more capacities and capabilities of the numerical MLPG method have been used. In order to validate the modeling and accuracy of calculations, the results have been compared with the findings of reference article [34] and [35].
Developing a construct to measure contractor project manager performance competencies
Authors: Kassa Rebecca , Ogundare Ibilola , Lines Brian , Smithwick Jake B. , Kepple Nancy J. , Sullivan Kenneth T. 
Published: November 2023

PurposeConstruction organizations' investment in effective talent-development programs is a key strategy in attracting, developing and retaining staff. Such programs are especially important given the current challenges in the construction workforce, including labor shortages, an aging workforce, generational differences in the workforce, supply chain disruptions and the need to effectively train staff in the skills that are essential in a constrained labor environment. To address these challenges, this study proposes a performance measurement strategy that construction companies can use as input to design their talent development programs.Design/methodology/approachThe strategy intends to assess the performance of project managers and develop criteria that define categories of their performance, including the top performers' category. This enables construction organizations to provide each project manager with individualized training that addresses areas of weakness and in turn, develops the skills that correspond with being top performers. The proposed strategy was developed and tested by surveying the immediate supervisors of 187 project managers working for general and specialty contractors in the United States. Principal component analysis was used to develop a single performance construct from seven performance criteria.FindingsThis construct was used to organize the project managers into the categories of top, above-average and below-average performers. According to the findings, top-performing project managers have well-rounded skills in the areas of leadership, communication, technical proficiency and overall job knowledge.Practical implicationsThe outcomes of this study can help construction organizations focus their talent-development programs on the skills most associated with PMs being top performers.Originality/valueThis study provides construction organizations with a comprehensive performance-measuring construct to focus their talent-development programs on the skills most associated with top-performing project managers. Researchers can use this study as a foundation for further understanding how performance is related to various construction professions.