bluuebunny/crossref_metadata_2025_split huggingface dataset:
A spiking neural network model of cortical intraregional metastability
Authors: Venkadesh Siva , Shaikh Asmir , Shakeri Heman , Barreto Ernest , Van Horn John D. 
Published: September 2022

AbstractTransient synchronization of bursting activity in neural networks, which occurs in patterns of metastable phase relationships between neurons, is a notable feature of network dynamics observedin vivo. However, the mechanisms that contribute to this dynamical complexity in neural circuits are not well understood. Local circuits in cortical regions consist of populations of neurons with diverse intrinsic oscillatory features. In this study, we numerically show that the phenomenon of transient synchronization, also referred to as metastability, emerges in an inhibitory neural population when the neurons’ intrinsic fast-spiking dynamics are appropriately modulated by slower inputs from an excitatory neural population. Using a compact model of a mesoscopic-scale network consisting of excitatory pyramidal and inhibitory fast-spiking neurons, our work demonstrates a relationship between the frequency of neural oscillations and the features of emergent metastability. In addition, a novel metric is formulated to characterize collective transitions in metastable networks. Finally, we discuss a blueprint to model the whole-brain resting-state dynamics using our scalable representation of intraregional network metastability.
evosim: fast and scalable stochastic simulations of evolutionary dynamics
Authors: Engelhardt Dalit , McDonald Thomas O. 
Published: September 2022

AbstractThe simulation of clonal dynamics with branching processes can provide valuable insights into disease progression and treatment optimization, but exact simulation of branching processes via the Stochastic Simulation Algorithm (SSA) is computationally prohibitive at the large population sizes associated with therapeutically-relevant scenarios. evosim is a versatile and flexible Python implementation of a fast and unbiased tau-leaping algorithm for the simulation of birth-death-mutation branching processes that is scalable to any population size. Package functionalities support the incorporation and tracking of a sequence of evolutionary changes such as therapeutic interventions as well as the analysis of population diversity. We show that runtimes scale logarithmically with population size, by contrast to the linear scaling of the SSA, and simulations exhibit strong agreement with SSA simulation results. These findings are also supported by mathematical results (Supplementary information).AvailabilityPackage, documentation, and tutorials / usage examples are available on GitHub (https://github.com/daliten/evosim). Mathematical details of the algorithm and the pseudocode are provided in the included Supplementary information.
Maternal cortisol and emotional complaints alter breast milk’s microbiome composition
Authors: Deflorin Nadia , Ehlert Ulrike , Amiel Castro Rita T. 
Published: September 2022

AbstractBreast milk (BM) is considered the “gold standard” of nutrition due to its many benefits for the infant. On the other hand, the challenges of pregnancy can lead to increased stress in some women, which may affect BM quality. Although studies have demonstrated a negative link between maternal psychopathology and child development, it remains unclear how maternal psychobiological changes can be intergenerationally transmitted.AimsWe investigated the associations between maternal biological stress, depressive symptoms, self-reported stress and anxiety symptoms and the BM microbiome. Further, we analysed these parameters in relation to BM glucocorticoid concentrations and explored the influence of BM glucocorticoids on BM bacterial composition.MethodsN=100 women completed standardised questionnaires (e.g. EPDS, STAI, GAS) at 34-36 weeks gestation and in the early postpartum; and sampled saliva at 34-36 and 38 weeks gestation. BM samples were collected in the early postpartum. Microbiota was analysed using 16S rRNA amplicon sequencing.ResultsPrenatal GAS and pregnancy-related symptoms (sum) were negatively correlated withAlphaproteobacteria(τ = - 0.2137, FDR = 0.0199*; τ = - 0.1805 FDR = 0.0798*), whereas in the postpartum period, the STAI-S scores were negatively correlated with different taxa. Postpartum-related symptoms (sum) were also linked to decreasedPropionibacteriales. Salivary cortisol AUCg at 34-36 weeks was negatively correlated withActinomycetia(τ = -0.1633, FDR = 0.0630*) andClostridia(τ = -0.1824, FDR = 0.0630*). BM cortisol was negatively correlated withStaphylococcus(τ = - 0.2047, FDR = 0.0885*) and positively correlated with BM alpha diversity. No associations emerged between psychobiological parameters and BM glucocorticoids.ConclusionsIncreased perinatal emotional complaints and prenatal cortisol AUCg were associated with decreased commensal bacteria, whereas enhanced BM cortisol was linked to increased alpha diversity and reducedStaphylococcus. These findings suggest a negative relation between high maternal psychobiological complaints and commensal milk microbiota.
Comprehensive analysis of intercellular communication in thermogenic adipose niche
Authors: Shamsi Farnaz , Zheng Rongbin , Ho Li-Lun , Chen Kaifu , Tseng Yu-Hua 
Published: September 2022

AbstractBrown adipose tissue (BAT) is responsible for regulating body temperature through adaptive thermogenesis. The ability of thermogenic adipocytes to dissipate chemical energy as heat counteracts weight gain and has gained considerable attention as a strategy against obesity. BAT undergoes major remodeling in a cold environment. This remodeling results from changes in the number and function of brown adipocytes, expanding the network of blood vessels and sympathetic nerves, and changes in the makeup and function of immune cells. All these processes are essential for enhanced BAT thermogenesis to maintain euthermia in the cold. Such synergistic adaptation requires extensive crosstalk between the individual cells in tissues to coordinate their responses. To understand the mechanisms of intercellular communication in BAT, we applied the CellChat algorithm to single-cell transcriptomic data of mouse BAT. We constructed an integrative network of ligand-receptor interactome in BAT and identified the major signaling input and output of each cell type. By comparing the ligand-receptor interactions in BAT of mice housed at different environmental temperatures, we found that cold exposure enhances the intercellular interactions among the major cell types in BAT, including adipocytes, adipocyte progenitors, lymphatic and vascular endothelial cells, myelinated Schwann cells (MSC), nonmyelinated Schwann cells (NMSC), and immune cells. Furthermore, we identified the ligands and receptors that are regulated at the transcriptional level by temperature. These interactions are predicted to regulate the remodeling of extracellular matrix (ECM), inflammatory response, angiogenesis, and neurite growth. Together, our integrative analysis of intercellular communications in BAT and their dynamic regulation in response to housing temperatures establishes a holistic understanding of the mechanisms involved in BAT thermogenesis. The resources presented in this study provide a valuable platform for future investigations of BAT development and thermogenesis.
CREB-pCREB-PER2 feedback loop mediates transition between mania and depression-like behaviors
Authors: Wang Xin-Ling 
Published: September 2022

AbstractLittle is known about the mechanisms underlying the transition between mania and depression. We found here that ouabain decreased pCREB and PER2 levels in CA1 and induced mania-like behavior, which was attenuated by lithium and overexpression ofPer2in this region. Furthermore, knockdown ofPer2in CA1 induced mania-like behavior, in contrast, overexpression ofPer2resulted in depression-like behavior. Similar results were found in manipulations ofCreb1in CA1. Western blot analyses revealed that upregulations of CREB or PER2 can increase each other’s levels, besides pCREB, and vice versa. Therefore, the CREB– pCREB–PER2 pathway forms a positive feedback loop that mediates the transition between manic and depressive phenotypes.One-Sentence SummaryA novel molecular loop underlies phase inversion of bipolar disorder
Characterisation of an Escherichia coli line that completely lacks ribonucleotide reduction yields insights into the evolution of obligate intracellularity
Authors: Arras Samantha D. M. , Sibaeva Nellie , Catchpole Ryan J. , Horinouchi Nobuyuki , Si Dayong , Rickerby Alannah M. , Deguchi Kengo , Hibi Makoto , Tanaka Koichi , Takeuchi Michiki , Ogawa Jun , Poole Anthony M. 
Published: September 2022

AbstractAll life requires ribonucleotide reduction for de novo synthesis of deoxyribonucleotides. A handful of obligate intracellular species are known to lack ribonucleotide reduction and are instead dependent on their host for deoxyribonucleotide synthesis. As ribonucleotide reduction has on occasion been lost in obligate intracellular parasites and endosymbionts, we reasoned that it should in principle be possible to knock this process out entirely under conditions where deoxyribonucleotides are present in the growth media. We report here the creation of a strain of E. coli where all three ribonucleotide reductase operons have been fully deleted. Our strain is able to grow in the presence of deoxyribonucleosides and shows slowed but substantial growth. Under limiting deoxyribonucleoside levels, we observe a distinctive filamentous cell morphology, where cells grow but do not appear to divide regularly. Finally, we examined whether our lines are able to adapt to limited supplies of deoxyribonucleosides, as might occur in the evolutionary switch from de novo synthesis to dependence on host production during the evolution of parasitism or endosymbiosis. Over the course of an evolution experiment, we observe a 25-fold reduction in the minimum concentration of exogenous deoxyribonucleosides necessary for growth. Genome analysis of replicate lines reveals that several lines carry mutations in deoB and cdd. deoB codes for phosphopentomutase, a key part of the deoxyriboaldolase pathway, which has been hypothesised as an alternative to ribonucleotide reduction for deoxyribonucleotide synthesis. Rather than synthesis via this pathway complementing the loss of ribonucleotide reduction, our experiments reveal that mutations appear that reduce or eliminate the capacity for this pathway to catabolise deoxyribonucleotides, thus preventing their loss via central metabolism. Mutational inactivation of both deoB and cdd is also observed in a number of obligate intracellular bacteria that have lost ribonucleotide reduction. We conclude that our experiments recapitulate key evolutionary steps in the adaptation to intracellular life without ribonucleotide reduction.
Late-life onset psychotic symptoms and incident cognitive impairment in people without dementia: modification by genetic risk for Alzheimer’s disease
Authors: Creese Byron , Arathimos Ryan , Aarsland Dag , Ballard Clive , Corbett Anne , Ismail Zahinoor 
Published: September 2022

ABSTRACTINTRODUCTIONLate-life onset psychosis is associated with faster progression to dementia in cognitively normal people, but little is known about its relationship to cognitive impairment in advance of dementia.METHODSClinical and genetic data from 2,750 people over 50 without dementia were analyzed. Incident cognitive impairment was operationalized using the IQCODE and psychosis (MBI-psychosis) was rated using the Mild Behavioral Impairment Checklist. The whole sample was analyzed before stratification on APOE-ε4 status.RESULTSIn Cox proportional hazards models, MBI-psychosis had a higher hazard rate (HR) for cognitive impairment relative to the No Psychosis group (HR:3.6, 95% CI:2.2-6, p<0.0001). The HR for MBI-psychosis was higher in APOE-ε4 carriers and there was an interaction between the two (HR for interaction: 3.4, 95% CI:1.2-9.8, p=0.02).DISCUSSIONPsychosis assessment in the MBI framework is associated with incident cognitive impairment in advance of dementia, these symptoms may be particularly important in the context of APOE genotype.
OVERVIEW OF RENAL OSTEODYSTROPHY IN BRAZIL: A CROSS-SECTIONAL STUDY
Authors: Carbonara Cinthia E. M. , Roza Noemi A. V. , dos Reis Luciene M. , Carvalho Aluízio B. , Jorgetti Vanda , de Oliveira Rodrigo Bueno 
Published: September 2022

ABSTRACTIntroductionEpidemiologic profile of renal osteodystrophy (ROD) is changing over time and cross-sectional studies provide essential information to improve care and health policies. The Brazilian Registry of Bone Biopsy (REBRABO) is a prospective, national-multicenter cohort that aims to provide clinical information on ROD.MethodsFrom Aug/2015-Dec/2021, clinical-demographic, laboratory and ROD information were included.ResultsData from 386 individuals were considered. Age was 52 (42–60) years; 198 (51%) were male; 315 (82%) were on hemodialysis; osteitis fibrosa (OF) [163 (42%)] and adynamic bone disease (ABD) [96 (25%)] were the most prevalent forms of ROD; 190 (49%) had the diagnosis of osteoporosis, 82 (56%) vascular calcification; 138 (36%) bone aluminum accumulation and 137 (36%) iron intoxication; patients with high turnover were prone to present a higher prevalence of symptoms.ConclusionsElevated proportion of patients were diagnosed with OF and ABD, as well as osteoporosis, vascular calcification and clinical symptoms.
Multiomics reveal that silk fibroin and sericin differentially potentiate the paracrine functions of mesenchymal stem cells and enhance tissue regeneration
Authors: Zhang Yanan , Sheng Renwang , Chen Jialin , Wang Hongmei , Zhu Yue , Cao Zhicheng , Zhao Xinyi , Wang Zhimei , Liu Chuanquan , Chen Zhixuan , Zhang Po , Kuang Baian , Zheng Haotian , Yao Qingqiang , Zhang Wei 
Published: September 2022

AbstractSilk fibroin (SF) and sericin (SS), the two major proteins of silk, are attractive biomaterials that show great potential in regenerative medicine. However, their biochemical interactions with stem cells were not fully understood. Here, we employed multiomics to obtain a global view of the triggered cellular processes and pathways of MSCs by SF and SS. Integrated RNA-seq and proteomics revealed that SF and SS strongly enhanced the paracrine activity of MSCs through differentially activating integrin and glycolytic pathways, rather than directly regulating stem cell fate to initiate multiple but distinct biological processes in MSCs. Those specific paracrine signals of MSCs stimulated by SF and SS effectively promoted skin wound healing by influencing the behaviors of multiple resident cells in skin wound microenvironments. This study provides comprehensive and reliable insights into the cellular interactions with SF and SS, enabling future development of silk-based therapeutics for tissue engineering and stem cell therapy.
Automated STED nanoscopy for high-throughput imaging of cellular structures
Authors: Mol Frank N. , Vlijm Rifka 
Published: September 2022

AbstractSTimulated Emission Depletion (STED) nanoscopy uniquely combines a high spatial resolution (20-50nm in cells) with relatively fast imaging (frame rate of ∼1-30Hz), straightforward sample preparation and direct image output (no postprocessing required). Although these characteristics in principle make STED very suitable for high-throughput imaging, only few steps towards automation have been made. Here, we have developed fully automated STED imaging, eliminating all manual steps including the selection and characterisation of the relevant (cellular) regions, sample focusing and positioning, and microscope adjustments. This automatic STED image acquisition increases the data output by roughly two orders of magnitude, resulting in a more efficient use of the high-end microscope, and the ability to detect and characterise objects that are only present in a small subset of the sample.
Exploring dose-response relationships inAedes aegyptisurvival upon bacteria and arbovirus infection
Authors: Rocha Mariana M. , Talyuli Octávio A. C. , Luíza Rulff da Costa Clara , Granella Lucilene W. , Mansur Daniel S. , Oliveira Pedro L. , Oliveira José Henrique M. 
Published: September 2022

AbstractA detailed understanding of host fitness changes upon variation in microbe density is a central aim of infection biology. Here, we applied dose-response curves to studyAedes aegyptisurvival upon exposure to different microbes. We challenged female mosquitoes withListeria monocytogenes, a model bacterial pathogen, Dengue 4 virus and Zika virus, two medically relevant arboviruses, to understand the distribution of mosquito susceptibility and net fitness (survival) following microbe exposure. By correlating microbe loads and host health, we found that a blood meal promotes survival in our systemic bacterial infection model and that mosquitoes orally infected with bacteria had an enhanced defensive capacity than insects infected through injection. We also showed thatAedes aegyptihas a higher survival profile upon arbovirus infection but, under the conditions tested, was more susceptible to Zika virus when compared to Dengue virus. Here, we applied a framework for the study of microbe-induced mosquito mortality detailing howAedes aegyptilifespan varies upon different inoculum sizes of bacteria and arboviruses.
Unraveling the intricate microtubule inner protein networks that reinforce mammalian sperm flagella
Authors: Leung Miguel Ricardo , Roelofs Marc C. , Chiozzi Riccardo Zenezini , Hevler Johannes F. , Heck Albert J. R. , Zeev-Ben-Mordehai Tzviya 
Published: September 2022

AbstractTo find and fuse with the egg, mammalian sperm must complete an arduous voyage through the female reproductive tract. The sperm cell’s remarkable odyssey is powered by its flagellum, a microtubule-based molecular machine ornamented with accessory structures that stabilize the sperm tail in viscous media. Recently, cryo-electron tomography (cryo-ET) revealed that mammalian sperm flagella are further reinforced at the molecular scale with sperm-specific microtubule inner proteins (sperm-MIPs), but the identities of these sperm-MIPs are unknown. Here, we use cryo-electron microscopy to resolve structures of native bovine sperm doublet microtubules, thus identifying most sperm-MIPs. In the A-tubule, several copies of testis-specific Tektin-5 contribute to an extended protein network spanning nearly the entire microtubule lumen. Different copies of Tektin-5 adopt a range of conformations and organizations based on their local interactions with other MIPs. The B-tubule is in turn stabilized by sperm-MIPs that bind longitudinally along and laterally across protofilaments. We further resolve structures of endpiece singlet microtubules, revealing MIPs shared between singlets and doublets. Our structures shed light on the molecular diversity of cilia across different cell types of the vertebrate body and provide a structural framework for understanding the molecular underpinnings of male infertility.
Transposon wave remodelled the epigenomic landscape in the rapid evolution of a novel X chromosome dosage compensation mechanism
Authors: Metzger David C.H. , Porter Imogen , Mobley Brendan , Sandkam Benjamin A. , Fong Lydia J.M. , Anderson Andrew P. , Mank Judith E. 
Published: September 2022

SummarySex chromosome dosage compensation is a model to understand the coordinated regulation of transcription, however the advanced age of the sex chromosomes in model systems make it difficult to study how the complex regulatory mechanisms underlying chromosome-wide dosage compensation can evolve. The sex chromosomes ofPoecilia pictahave undergone recent and rapid divergence, resulting in widespread gene loss on the male Y, coupled with complete X chromosome dosage compensation, the first case reported in a fish. Thede novoorigin of a novel dosage compensation system presents a unique opportunity to discover new mechanisms of gene regulation and their evolutionary origins. By combining a new chromosome-level assembly ofP. pictawith whole-genome bisulfite sequencing and RNA-Seq data, we determine that the binding motif of Yin Yang 1 (YY1) is associated with male hypomethylated regions on the X, but not the autosomes. The male-specific hypomethylation of these motifs offers a putative model for male specific upregulation of genes on the X. These YY1 motifs are the result of a recent and rapid repetitive element expansion on theP. pictaX chromosome, which is absent in closely related species that lack dosage compensation. Taken together, our results present compelling support that a disruptive wave of repetitive element insertions carrying YY1 motifs resulted in the remodeling of the X chromosome epigenomic landscape and the de novo origin of a new dosage compensation mechanism.
Mycelial differentiation linked avermectin production in Streptomyces avermitilis studied with Raman imaging
Authors: Horii Shumpei , Samuel Ashok Zachariah , Nakashima Takuji , Take Akira , Matsumoto Atsuko , Takahashi Yoko , Ando Masahiro , Takeyama Haruko 
Published: September 2022

AbstractStreptomyces avermitilis is a gram-positive bacterium that undergoes complex physiological and morphological differentiation during its life cycle, which has implications in secondary metabolites production. Avermectin, produced by S. avermitilis, is widely used as an anthelmintic and insecticidal agent. In this study, we have applied Raman microspectroscopic imaging to elucidate the correlation between production of avermectin and the morphological differentiation in S. avermitilis. We demonstrate distinctive variations in the localization of avermectin at various morphological stages, such as, substrate mycelium, spore-bearing mycelium, spiral spore chains under solid culture conditions. Under liquid culture condition, however, avermectin is detected only in mycelia after early MII stage of differentiation. Morphological differentiation was observed in liquid and solid cultures, but the chemical profiles of the mycelia were substantially different. Spherical bodies containing avermectin with characteristically different chemical composition to that of spores were also observed under solid culture, which suggests possible release of extracellular vesicles (EVs).Key pointsAvermectin production is regulated during mycelial differentiationLiquid and solid culture conditions affects mycelial differentiationRaman microspectroscopic analysis reveals localization profiles of avermectin
Examining strategic antecedents of the appointment of women to top management teams
Authors: Bonner Robert L. , Hyde Steven J. , Faile Kristen 
Published: September 2022

PurposeThe purpose of this study is to examine the organizational and environmental antecedents to the appointment of a woman to a non-CEO top management team (TMT) position.Design/methodology/approachThis study uses a conditional fixed effects logistic regression model to analyze non-CEO TMT appointment data collected from the S&P 500 between 2008 and 2016.FindingsWomen were more likely to be appointed to non-CEO TMT positions when a firm was undergoing strategic change, had slack resources, and was in a less munificent environment.Originality/valueThis article contributes to the literature concerning the antecedents of the selection of women to executive leadership (e.g. the glass cliff) roles by examining organizational and environmental contexts at the non-CEO TMT unit of analysis.