bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aerobic exercise training selectively improves cortical inhibitory function after stroke
Authors: Palmer Jacqueline A , Whitaker Alicen A , Payne Aiden M , Bartsch Bria L , Reisman Darcy S , Boyne Pierce E , Billinger Sandra A 
Published: November 2022

AbstractBackgroundAerobic exercise elicits striking effects on neuroplasticity and cognitive executive function but is poorly understood after stroke.ObjectiveWe tested the effect of 4 weeks of aerobic exercise training on inhibitory and facilitatory elements of cognitive executive function and electroencephalography (EEG) markers of cortical inhibition and facilitation. We investigated relationships between stimulus-evoked cortical responses, blood lactate levels during training, and aerobic fitness post-intervention.MethodsTwelve individuals with chronic (>6mo) stroke completed an intensive aerobic exercise intervention (40-mins, 3x/week). Electroencephalography and motor response times were assessed during congruent (response facilitation) and incongruent (response inhibition) stimuli of a Flanker task. Aerobic fitness capacity was assessed as VO2-peak during a treadmill test pre- and post-intervention. Blood lactate was assessed acutely (<1 min) after exercise each week. Cortical inhibition (N2) and facilitation (frontal P3) were quantified as peak amplitudes and latencies of stimulus evoked EEG activity over the frontal cortical region.ResultsFollowing exercise training, the response inhibition speed increased while response facilitation remained unchanged. A relationship between earlier cortical N2 response and faster response inhibition emerged post-intervention. Individuals who produced higher lactate during exercise training achieved faster response inhibition and tended to show earlier cortical N2 responses post-intervention. There were no associations between VO2-peak and metrics of behavioral or neurophysiologic function.ConclusionsThese findings provide novel evidence for selective benefits of aerobic exercise on inhibitory control during the initial 4-week period after initiation of exercise training, and implicate a potential therapeutic effect of lactate on post-stroke cortical inhibitory function.Trial RegistrationClinicalTrials.govIdentifier:NCT03760016. First posted: November 30, 2018.https://clinicaltrials.gov/ct2/show/NCT03760016
The Molecular Endotypes of Type 1 and Type 2 SLE
Authors: Robl Robert D. , Eudy Amanda M. , Bachali Prathyusha S. , Rogers Jennifer L. , Clowse Megan E.B. , Pisetsky David S. , Lipsky Peter E. 
Published: November 2022

ABSTRACTObjectiveTo characterize the molecular landscape of patients with Type 1 and Type 2 systemic SLE erythematosus (SLE) by analyzing gene expression profiles from peripheral blood.MethodsFull transcriptomic RNA sequencing was carried out on whole blood samples from 18 subjects with SLE selected by the presence of manifestations typical of Type 1 and Type 2 SLE. The top 5,000 row variance genes were analyzed by Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) to generate gene co-expression modules, that were functionally annotated and correlated to various demographic traits, clinical features and laboratory measures.ResultsExpression of specific gene coexpression modules correlated with individual features of Type 1 and 2 SLE and also effectively segregated samples from Type 1 from Type 2 SLE patients. Unique Type 1 SLE enrichments included IFN, monocytes, T cells, cell cycle, and neurotransmitter pathways, whereas unique Type 2 SLE enrichments included B cells and metabolic and neuromuscular pathways. Gene co-expression modules of Type 2 SLE patients were identified in subsets of previously reported patients with inactive SLE and idiopathic fibromyalgia (FM) and also identified subsets of patients with active SLE with a greater frequency of severe fatigue.ConclusionGene co-expression analysis successfully identified unique transcriptional patterns that segregate Type 1 SLE from Type 2 SLE and further identified Type 2 molecular features in patients with inactive SLE or FM and with active SLE with severe fatigue.
Multi-centric evaluation of Biomeme Franklin Mobile qPCR for rapid detection ofMycobacterium ulceransin clinical specimens
Authors: Frimpong Michael , Frimpong Venus Nana Boakyewaa , Numfor Hycenth , Donkeng Valerie , Amedior Jennifer Seyram , Deegbe Daniella Emefa , Dadson Baaba , Ablordey Anthony , Eyangoh Sara , Phillips Richard , Vedithi Sundeep Chaitanya 
Published: November 2022

AbstractThe gold standard forMycobacterium ulceransdetection is PCR due to its high accuracy in confirmation of suspected cases. But the available PCR assays are design for standard size thermocyclers which are immobile and suited for reference laboratories far away from endemic communities. This makes it a challenge to obtain immediate results for patient management. We have validated and evaluated a dried reagent-based PCR assay adapted for a handheld, battery-operated, portable thermocycler with the potential of extending diagnostics to endemic communities with limited infrastructure. The diagnostic accuracy of the assay following a multi-centre evaluation by three Buruli ulcer reference laboratories with over 300 clinical samples showed sensitivity and specificity of 100% - 97% and 100% - 94%. This assay coupled with a field-friendly extraction method fulfill almost all the target product profile of Buruli ulcer for decentralized testing at districts, health centres and community level. A key critical action for achieving the NTD Road Map 2030 target for Buruli ulcer.
Antagonistic antimalarial properties of a methoxyamino chalcone derivative and 3-hydroxypyridinones in combination with dihydroartemisinin againstPlasmodium falciparum
Authors: Kampoun Tanyaluck , Koonyosying Pimpisid , Ruangsuriya Jetsada , Prommana Parichat , Shaw Philip J. , Kamchonwongpaisan Sumalee , Suwito Hery , Puspaningsih Ni Nyoman Tri , Uthaipibull Chairat , Srichairatanakool Somdet 
Published: November 2022

AbstractThe spread of artemisinin (ART)-resistantPlasmodium falciparumthreatens the control of malaria and mutations in the propeller domains ofP. falciparumKelch13 (k13) are strongly associated with the resistance. Ferredoxin (Fd) in the ferredoxin/NADP+reductase (Fd/FNR) redox system is essential for isoprenoid precursor synthesis in the plasmodial apicoplast; nonetheless, mutations of Fd gene (fd) may modulate ART resistance and Fd would be an important target for antimalarial drugs. We investigated the inhibitory effects of dihydroartemisinin (DHA), methoxyamino chalcone (C3), and iron chelators including deferiprone (DFP), 1-(N-acety1-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and deferiprone-resveratrol hybrid (DFP-RVT) against the growth of wild-type (WT)P. falciparumparasites and those withk13andfdmutations. C3 showed antimalarial potency similar to the iron chelators. Surprisingly, combined treatments of DHA with the C3 or iron chelators showed moderately antagonistic effects against P. falciparum growth. No differences were observed among the mutant parasites with respect to their sensitivity to C3 and the chelators, or the interactions of these compounds with DHA. The data suggest that inhibitors of the Fd/FNR redox system should be avoided as ART partner drugs in ART combination therapy for treating malaria.
Identifying Strong Modulators of Cellular Quiescence Depth Across Different Quiescent Cells and Conditions
Authors: Lu Eric , Yao Guang 
Published: November 2022

ABSTRACTThe proper balance and transition between cellular quiescence and proliferation are critical to tissue homeostasis, repair, and regeneration. The likelihood of quiescence-to-proliferation transition is inversely correlated with quiescence depth, and deep quiescent cells are less likely to exit quiescence and reenter the cell cycle than shallow quiescent cells. The regulatory mechanisms of quiescence depth are poorly understood but essential for developing strategies against hypo- or hyper-proliferation diseases such as aging and cancer. Our earlier studies have demonstrated that the activation threshold of the bistable Rb-E2F gene network switch (ThE2F) controls quiescence depth. We have also identified coarse- and fine-tuning ThE2Fmodulators in rat embryonic fibroblasts. To examine whether other quiescent cells (including most adult stem and progenitor cells) under different environmental conditions use the same or different modulators of quiescence depth, here we studied the behaviors of 30,000 theoretical quiescent cell models that each support a functional Rb-E2F bistable switch with a unique parameter set. We found that although the vastly heterogeneous quiescent cell models exhibited no apparent parameter patterns, they converged at two alternative groups of strong quiescence-depth modulators (G1 cyclin/cdk-related and Rb/E2F complex-related). Our further machine learning (decision tree) analysis suggested that the Rb protein level and dephosphorylation rate in quiescent cells determine which modulator group to use to regulate quiescence depth.
Homeotic compartment curvature and tension control spatiotemporal folding dynamics
Authors: Villedieu Aurélien , Alpar Lale , Gaugue Isabelle , Joudat Amina , Graner François , Bosveld Floris , Bellaïche Yohanns 
Published: November 2022

AbstractShape is a conspicuous and fundamental property of biological systems entailing the function of organs and tissues. While much emphasis has been put on how tissue tension and mechanical properties drive shape changes, whether and how a given tissue geometry influences subsequent morphogenesis remains poorly characterized. Here, we explored how curvature, a key descriptor of tissue geometry, impinges on the dynamics of epithelial tissue invagination. We found that the morphogenesis of the fold separating the adultDrosophilahead and thorax segments is driven by the invagination of the Deformed (Dfd) homeotic compartment. Dfd controls invagination by modulating actomyosin organization and in-plane epithelial tension via the Tollo and Dystroglycan receptors. By experimentally introducing curvature heterogeneity within the homeotic compartment, we established that a curved tissue geometry converts the Dfd-dependent in-plane tension into an inward force driving folding. Accordingly, the interplay between in-plane tension and tissue curvature quantitatively explains the spatiotemporal folding dynamics. Collectively, our work highlights how genetic patterning and tissue geometry provide a simple design principle driving folding morphogenesis during development.
Long-read genomes reveal pangenomic variation underlying yeast phenotypic diversity
Authors: Weller Cory A. , Andreev Ilya , Chambers Michael J. , Park Morgan ,   NISC Comparative Sequencing Program, Bloom Joshua S. , Sadhu Meru J. 
Published: November 2022

AbstractUnderstanding the genetic causes of trait variation is a primary goal of genetic research. One way that individuals can vary genetically is through the existence of variable pangenomic genes – genes that are only present in some individuals in a population. The presence or absence of entire genes could have large effects on trait variation. However, variable pangenomic genes can be missed in standard genotyping workflows, due to reliance on aligning short-read sequencing to reference genomes. A popular method for studying the genetic basis of trait variation is linkage mapping, which identifies quantitative trait loci (QTLs), regions of the genome that harbor causative genetic variants. Large-scale linkage mapping in the budding yeastSaccharomyces cerevisiaehas found thousands of QTLs affecting myriad yeast phenotypes. To enable the resolution of QTLs caused by variable pangenomic genes, we used long-read sequencing to generate highly complete de novo assemblies of 16 diverse yeast isolates. With these assemblies we resolved growth QTLs to specific genes that are absent from the reference genome but present in the broader yeast population at appreciable frequency. Copies of genes also recombine onto chromosomes where they are absent in the reference genome, and we found that these copies generate additional QTLs whose resolution requires pangenome characterization. Our findings demonstrate the power of long-read sequencing to identify the genetic basis of trait variation.
Short heat shock has a long-term effect on mesenchymal stem cells’ transcriptome
Authors: Ribarski-Chorev Ivana , Schudy Gisele , Strauss Carmit , Schlesinger Sharon 
Published: November 2022

AbstractThe harmful consequences of heat stress (HS) on physiology are well documented, but the molecular aspects of changing thermal conditions are poorly understood. Therefore, a better understanding of the effects of this stress on the morphology, phenotype, proliferative capacity, and fate decision of MSCs is required. Our thorough characterization of MSCs’ transcriptome showed a major effect of HS on the transcriptional landscape. Specifically, examining the effect after three days of moderate HS shows changes in many cell processes, such as immune response, cell cycle, and differentiation. Surprisingly, we detected a long-term effect on cell identity even after short stress, possibly through the activation of bivalent genes related to cell lineage decisions. Finally, comparing the differentially expressed genes following short HS with their transcriptional state after three days of recovery, we find transient upregulation of many members of the MLL family and other histone modifiers; a finding which offers a potential mechanistic account for the stable bivalent genes activation. This could be used to predict and modify the long-term effect of HS on cell identity.Summary blurbHeat shock alters mesenchymal stem cells’ transcriptional programs, resulting in stable activation of lineage commitment genes, thus explaining the shift in the identity and fate of the cells.Graphical abstract
Global connectivity and networks of marine reserves
Authors: McDowell Julia , Andrello Marco , Velez Laure , Barrier Nicolas , Manel Stephanie , Pollock Laura J. , Mouillot David 
Published: November 2022

AbstractCooperation between countries in managing and protecting shared marine resources is beneficial both ecologically and economically, but how best to establish the cooperation needed at a global scale is largely unknown. Here, we used hydrodynamic modelling to identify ecologically connected networks of marine reserves (MRs) and evaluated these networks with socio-economic indicators. Most of the networks are homogenous with similar levels of development, shared languages, and other cultural values. However, we found that 17% (11/66) of the largest networks (>20 MRs) span multiple countries. These heterogenous networks are composed of countries with different economic, political, and cultural views. Countries that control more, larger marine reserves also have a more even ratio of source reserves to sinks. We discuss that, while such economic and cultural homogeneity might lead to more efficient ecological management in the short term, heterogeneous networks may prove to be more resilient in the longer term, when climate change will modify marine connectivity.
Architecture of chloroplast TOC-TIC translocon supercomplex
Authors: Liu Hao , Li Anjie , Rochaix Jean-David , Liu Zhenfeng 
Published: November 2022

SummaryChloroplasts rely on the translocon complexes in the outer and inner envelope membranes (termed TOC and TIC, respectively) to import thousands of different nuclear-encoded proteins from the cytosol1–4. While previous studies indicated that the TOC and TIC complexes may assemble into larger supercomplexes5–7, the overall architectures of the TOC-TIC supercomplexes and the mechanism of preprotein translocation are elusive. Here we report the cryo-electron microscopy (cryo-EM) structure of the TOC-TIC supercomplex fromChlamydomonas reinhardtiiat an overall resolution of 2.8 Å. The major subunits of the TOC complex (Toc75, Toc90 and Toc34) and TIC complex (Tic214, Tic20, Tic100 and Tic56), three chloroplast translocon-associated proteins (Ctap3, Ctap4 and Ctap5) and three newly-identified small inner-membrane proteins (Simp1-3) have been located in the supercomplex. As the largest protein, Tic214 traverses the inner membrane, the intermembrane space and the outer membrane, connecting the TOC complex with the TIC proteins. An inositol hexaphosphate (InsP6 or I6P) molecule is located at the Tic214-Toc90 interface and stabilizes their assembly. Moreover, four lipid molecules are located within or above an inner-membrane funnel formed by Tic214, Tic20, Simp1 and Ctap5. Furthermore, multiple potential pathways found in the TOC-TIC supercomplex may support translocation of different substrate preproteins into chloroplasts.
Polymorphic regions in BA.2.12.1, BA.4 and BA.5 likely implicated in immunological evasion of Omicron subvariant BQ.1.1
Authors: Felix Pierre Teodosio 
Published: November 2022

SummaryIn this work, 45 Spike glycoprotein Chain B polypeptides were used in the subvariants BA.2.12.1, BA.4 and BA.5 were recovered from GENBANK. All sequences were publicly available on the National Biotechnology Information Center (NCBI) platform. The results indicate the existence of informative polymorphic and parsimony sites that may be implicated in the level of diversity of the studied strains, as well as reflect the immunological evasion potential of the subvariant BQ1.1. of the variant Ômicron d and SARS-CoV-2. The results also suggest the formation of ancestral polymorphism with slight retention, and the probable is responsible the diversity of the whole studied set.
Decoding protein binding landscape on circular RNAs with base-resolution Transformer models
Authors: Wu Hehe , Fang Yi , Yang Yang , Pan Xiaoyong , Shen Hong-Bin 
Published: November 2022

AbstractCircular RNAs (circRNAs) interact with RNA-binding proteins (RBPs) to modulate gene expression. To date, most computational methods for predicting RBP binding sites on circRNAs focus on circRNA fragments instead of circRNAs. These methods detect whether a circRNA fragment contains binding sites, but cannot determine where are the binding sites and how many binding sites are on the circRNA transcript. We report a hybrid deep learning-based tool, CircSite, to predict RBP binding sites at single-nucleotide resolution and detect key contributed nucleotides on circRNA transcripts. CircSite takes advantage of convolutional neural networks (CNNs) and Transformer for learning local and global representations of circRNAs binding to RBPs, respectively. We construct 37 datasets of RBP-binding circRNAs for benchmarking and the experimental results show that CircSite offers accurate predictions of RBP binding nucleotides and detects key subsequences aligning well with known binding motifs.
The mutational signatures of poor treatment outcomes on the drug-susceptibleMycobacterium tuberculosisgenome
Authors: Chen Yiwang , Jiang Qi , Peierdun Mijiti , Takiff Howard E. , Gao Qian 
Published: November 2022

ABSTRACTDrug resistance is a known risk factor for poor tuberculosis (TB) treatment outcomes, but the contribution of other bacterial factors to poor outcomes in drug susceptible TB is less understood. Here, we generate a population-based dataset of drug-susceptibleMycobacterium tuberculosis(MTB) isolates from China to identify factors associated with poor treatment outcomes. We sequenced the whole genome of 3496 MTB strains and linked genomes to patient epidemiological data. A genome-wide association study (GWAS) was performed to identify bacterial genomic variants associated with poor outcomes. Risk factors identified by logistic regression analysis were used in clinical models to predict treatment outcomes and their associations were assessed with structural equation models (SEM). GWAS identified fourteen MTB variants (24.2% vs 7.5%, P<0.001) and ade novoreactive oxygen species (ROS) mutational signature (26.3%±18.2% vs 22.9%±13.8%, P=0.027) that were more frequent in patients with poor treatment outcomes. Patient age, sex, and duration of diagnostic delay were also independently associated with poor outcomes. The best clinical prediction model, with an AUC of 0.74, incorporates both host and bacterial risk factors, and host factors are more important. Together, our results reveal that although host factors are the most important determinants for poor treatment outcomes, the genomic characteristics of the infecting MTB strain may also contribute significantly to poor treatment outcomes. Fourteen genetic variants were statistically associated with poor TB treatment outcomes, but the optimal model for predicting treatment outcomes includes both patient characteristics and bacterial genomic determinants.
Open-source versatile 3D-print animal conditioning platform design for in-vivo preclinical brain imaging in awake mice and anesthetized mice and rats
Authors: Gironda Zakia Ben Youss , Arefin Tanzil Mahmud , Qayyum Sawwal , Zhang Jiangyang , Wadghiri Youssef Zaim , Alon Leeor , Yaghmazadeh Omid 
Published: November 2022

ABSTRACTProper animal conditioning is a key factor in the quality and success of preclinical neuroimaging applications. We introduce an open-source easy-to-modify multi-modal 3D printable design for rodent conditioning for magnetic resonance imaging (MRI) or other imaging modalities. Our design can be used for brain imaging in anesthetized or awake mice and anesthetized rats. We show ease-of-use and reproducibility of subject conditioning with anatomical T2-weighted imaging for both mice and rats. We also demonstrate application of our design for awake fMRI in mice using both visual evoked potential and olfactory stimulation paradigms. In addition, we demonstrate that our proposed cradle design can be extended to multiple imaging modalities combining MRI, Positron emission tomography and X-ray computed tomography.
Management-control-system configurations in medium-sized mechanical-engineering firms: an exploratory analysis
Authors: Santini Fabio , Elisei Luca , Malmi Teemu , Scrucca Luca 
Published: November 2022

Purpose
Interest has grown in how management controls operate together as a package of interrelated mechanisms. This study aims to contribute to the topic by focusing on a single industry in one country, addressing controls in medium-sized enterprises (MEs). It explores how accounting and other forms of control commonly combine and the associations these combinations have with firm characteristics and context.

Design/methodology/approach
This study used a cross-sectional sample of 242 firms. Data were collected in 2015 from a survey of the Italian mechanical-engineering industry.

Findings
The MEs studied used two different control configurations. One group relatively strongly emphasized most studied controls, except for centralizing decision-making and strong hierarchy; the other relied on centralization and emphasized other controls less. Size, task programmability, outcome measurability, complexity in terms of the extensiveness of the product range and environmental unpredictability can predict the configuration in use.

Originality/value
No broad-based empirical evidence on control configurations in MEs currently exists. Previous research has focused on to what extent control systems affect business effectiveness or efficiency, without assessing how, and in which contexts, they combine.