bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of psychosocial interventions for hypertensive disorders in pregnancy: A systematic review and meta-analysis
Authors: Nnate Daniel A. , Ajayi Kobi V. , Hossain Md Mahbub , Guerby Paul 
Published: January 2022

ABSTRACTObjectiveStudies on psychosocial interventions for perinatal mental health and wellbeing are mostly limited to the postpartum period. However, the physiological changes associated with hypertensive disorders in pregnancy predisposes women to severe psychological distress and adverse birth outcomes. This review investigated the effectiveness of psychosocial interventions for hypertensive disorders during pregnancy.MethodsCochrane CENTRAL, Embase, MEDLINE, MIDIRS, CINAHL, PsycINFO, PsycArticles, and Web of Science were searched up to 22nd August 2021. Effect sizes on relevant health outcomes were pooled in a meta-analysis using STATA software.ResultsEight randomised trials involving 460 participants met the inclusion criteria. Included studies adopted several interventions ranging from music, exercise, cognitive behavioural therapy (CBT), spiritual care education and psychoeducation. The pooled effect showed a significant reduction in anxiety (d= −0.35 [−0.58, −0.11], p=0.004) and depression (d= −0.37 [−0.57, −0.17], p=0.0003). Spiritual care education significantly reduced postpartum stress disorder (d= −62.00 [−93.10, −30.90], p= 0.0001). However, CBT showed no effect on gestational stress (d= −2.20 [-4.89, 0.48], p= 0.11).ConclusionThis study provides satisfactory evidence that psychosocial interventions may likely reduce anxiety and depression associated with hypertensive disorders in pregnancy. However, the evidence is very uncertain about its effect on neonatal outcomes.Summary of findings
Estimating the relative proportions of SARS-CoV-2 strains from wastewater samples
Authors: Pipes Lenore , Chen Zihao , Afanaseva Svetlana , Nielsen Rasmus 
Published: January 2022

AbstractWastewater surveillance has become essential for monitoring the spread of SARS-CoV-2. The quantification of SARS-CoV-2 RNA in wastewater correlates with the Covid-19 caseload in a community. However, estimating the proportions of different SARS-CoV-2 strains has remained technically difficult. We present a method for estimating the relative proportions of SARS-CoV-2 strains from wastewater samples. The method uses an initial step to remove unlikely strains, imputation of missing nucleotides using the global SARS-CoV-2 phylogeny, and an Expectation-Maximization (EM) algorithm for obtaining maximum likelihood estimates of the proportions of different strains in a sample. Using simulations with a reference database of >3 million SARS-CoV-2 genomes, we show that the estimated proportions accurately reflect the true proportions given sufficiently high sequencing depth and that the phylogenetic imputation is highly accurate and substantially improves the reference database.
Inhibition of the JAK/STAT pathway with baricitinib reduces the multiple organ dysfunction caused by hemorrhagic shock in rats
Authors: Patel Nikita Mayur , Collotta Debora , Aimaretti Eleonora , Alves Gustavo Ferreira , Kröller Sarah , Coldewey Sina Maren , Collino Massimo , Thiemermann Christoph 
Published: January 2022

AbstractObjectiveThe aim of this study was to investigate (a) the effects of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway inhibitor (baricitinib) on the multiple organ dysfunction syndrome (MODS) in a rat model of hemorrhagic shock (HS) and (b) whether treatment with baricitinib attenuates the activation of JAK/STAT, NF-κB and NLRP3 caused by HS.BackgroundPost-traumatic MODS, which is in part due to excessive systemic inflammation, is associated with high morbidity and mortality. The JAK/STAT pathway is a regulator of numerous growth factor and cytokine receptors and, hence, is considered a potential master regulator of many inflammatory signaling processes. However, its role in trauma-hemorrhage is unknown.MethodsAn acute HS rat model was performed to determine the effect of baricitinib on MODS. The activation of JAK/STAT, NF-κB and NLRP3 pathways were analyzed by western blotting in the kidney and liver.ResultsWe demonstrate here for the first time that treatment with baricitinib (during resuscitation following severe hemorrhage) attenuates the organ injury and dysfunction and the activation of JAK/STAT, NF-κB and NLRP3 pathways caused by HS in the rat.ConclusionsOur results point to a role of the JAK/STAT pathway in the pathophysiology of the organ injury and dysfunction caused by trauma/hemorrhage and indicate that JAK inhibitors, such as baricitinib, may be repurposed for the treatment of the MODS after trauma and/or hemorrhage.
Population demography maintains biogeographic boundaries
Authors: Schmidt Chloé , Muñoz Gabriel , Lancaster Lesley T. , Lessard JP , Marske Katharine A. , Marshall Katie E. , Garroway Colin J. 
Published: January 2022

AbstractGlobal biodiversity is organized into biogeographic regions that comprise distinct biotas. The contemporary factors maintaining differences in species composition between biogeographic regions are poorly understood. Given the evidence that populations with sufficient genetic variation can adapt to fill new habitats, it is surprising that we do not see more homogenization of species assemblages among regions. Theory suggests that the expansion of populations across biogeographic transition zones could be limited by environmental gradients that affect population demography in ways that could limit adaptive capacity, but this has not been empirically explored. Using three independently curated data sets describing continental patterns of mammalian demography and population genetics, we show that populations closer to biogeographic transition zones have lower effective population sizes and genetic diversity, and are more genetically differentiated. These patterns are consistent with reduced adaptive capacity near biogeographic transition zones. The consistency of these patterns across mammalian species suggests they are stable, predictable, and generalizable in their contribution to long-term limits on expansion and homogenization of biodiversity across biogeographic transition zones. Understanding the contemporary processes acting on populations that maintain differences in the composition of regional biotas is crucial for our basic understanding of the current and future organization of global biodiversity. The importance of contemporary, population-level processes on the maintenance of global biogeographic regions suggests that biogeographic boundaries are susceptible to environmental perturbation associated with human-caused global change.
Single cell mutant selection for metabolic engineering of actinomycetes
Authors: Akhgari Amir , Baral Bikash , Koroleva Arina , Siitonen Vilja , Fewer David P. , Melançon Charles E. , Rahkila Jani , Metsä-Ketelä Mikko 
Published: January 2022

AbstractActinomycetes are important producers of pharmaceuticals and industrial enzymes. However, wild type strains require laborious development prior to industrial usage. Here we present a generally applicable reporter-guided metabolic engineering tool based on random mutagenesis, selective pressure, and single-cell sorting. We developed fluorescence-activated cell sorting (FACS) methodology capable of reproducibly identifying high-performing individual cells from a mutant population directly from liquid cultures. Genome-mining based drug discovery is a promising source of bioactive compounds, which is complicated by the observation that target metabolic pathways may be silent under laboratory conditions. We demonstrate our technology for drug discovery by activating a silent mutaxanthene metabolic pathway in Amycolatopsis. We apply the method for industrial strain development and increase mutaxanthene yields 9-fold to 99 mg l−1 in a second round of mutant selection. Actinomycetes are an important source of catabolic enzymes, where product yields determine industrial viability. We demonstrate 5-fold yield improvement with an industrial cholesterol oxidase ChoD producer Streptomyces lavendulae to 20.4 U g−1 in three rounds. Strain development is traditionally followed by production medium optimization, which is a time-consuming multi-parameter problem that may require hard to source ingredients. Ultra-high throughput screening allowed us to circumvent medium optimization and we identified high ChoD yield production strains directly from mutant libraries grown under preset culture conditions. In summary, the ability to screen tens of millions of mutants in a single cell format offers broad applicability for metabolic engineering of actinomycetes for activation of silent metabolic pathways and to increase yields of proteins and natural products.
Histone chaperones exhibit conserved functionality in nucleosome remodeling
Authors: Buzón P. , Velázquez-Cruz A. , González-Arzola K. , Díaz-Quintana A. , Díaz-Moreno I. , Roos W.H. 
Published: January 2022

AbstractChromatin homeostasis mediates some of the most fundamental processes in the eukaryotic cell. In this regard, histone chaperones have emerged as major regulatory factors during DNA replication, repair, and transcription. However, the dynamic nature of these processes has severely impeded their characterization at the molecular level. Here we apply single-molecule probing by fluorescence optical tweezers to follow histone chaperone dynamics in real-time. The molecular action of SET/template-activating factor-Iβ and nucleophosmin 1—representing the two most common histone chaperone folds—were examined using both nucleosomes and isolated core histones. We show that these chaperones present binding specificity for partially dismantled nucleosomes and are able to recognize and disrupt non-native histone-DNA interactions. Furthermore, we reveal that cytochrome c inhibition of histone chaperones is coupled to chaperone accumulation on DNA-bound histones. Our single-molecule approach shows that despite the drastically different structures of these chaperones, they present conserved modes of action mediating nucleosome remodeling.
Overexpression of miR5505 enhanced drought and salt resistance in rice (Orayza sativa)
Authors: Fan Yuanwei , Xie Jiankun , Zhang Fantao 
Published: January 2022

AbstractRice is one of the most important crops in the world and half of the world population consumes it as their staple food. The abiotic stresses caused by drought, salt and other stresses have severely impacted rice production. MicroRNAs (miRNAs) are a type of small non-coding RNAs which widely reported as gene regulators, suppressing genes expression by degradation mRNA or translation inhibition. Previously, high-throughput sequencing has found a conserved miRNA miR5505 responding to drought stress in Dongxiang wild rice (DXWR). Several other studies also revealed that miR5505 was involved in rice stress responses. We further studied the effect of miRNA in drought and salt tolerance by overexpression it in rice. 2 in 18 successfully transformed transgenic lines with higher miR5505 expression were selected and then drought and salt resistance ability were evaluated. Both transgenic lines showed stronger drought and salt tolerance than wild-type (WT). Putative targets of miR5505 were identified by psRNATarget and several of them were found stress-related. RNA-seq found 1,980 differentially expressed genes (DEGs) in transgenic lines. Among them, 978 genes were down-regulated. Three genes were predicted by psRNATarget and two of them might be stress-related. We also found various environmental stresscis-acting elements in upstream of miR5505 promoter through Software PlantCARE. In all, we improved rice drought and salt tolerance by overexpressing miR5505, and the generated putative targets andcis-acting elements also suggested miR5505 might play important roles in the regulation of drought and salt responses.
Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021
Authors: Caliendo V. , Lewis N. S. , Pohlmann A. , Baillie S.R. , Banyard A.C. , Beer M. , Brown I.H. , Fouchier R.A.M. , Hansen R.D.E. , Lameris T.K. , Lang A.S. , Laurendeau S. , Lung O. , Robertson G. , van der Jeugd H. , Alkie T.N. , Thorup K. , van Toor M.L. , Waldenström J. , Yason C. , Kuiken T. , Berhane Y. 
Published: January 2022

AbstractHighly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage (GsGd), which threaten the health of poultry, wildlife and humans, are spreading across Asia, Europe and Africa, but are currently absent from Oceania and the Americas. In December 2021, H5N1 HPAI viruses were detected in poultry and a free-living gull in St. John’s, Newfoundland and Labrador, Canada. Phylogenetic analysis showed that these viruses were most closely related to HPAI GsGd viruses circulating in northwestern Europe in spring 2021. Analysis of wild bird migration suggested that these viruses may have been carried across the Atlantic via Iceland, Greenland/Arctic or pelagic routes. The here documented incursion of HPAI GsGd viruses into North America raises concern for further virus spread across the Americas by wild bird migration.One-Sentence SummaryDetection of H5N1 highly pathogenic avian influenza in Canada raises concern for spread in the Americas by migratory birds.
Standard selection treatments with sulfadiazine limit Plasmodium yoelii host-to-vector transmission
Authors: Rios Kelly T. , Dickson Taylor M. , Lindner Scott E. 
Published: January 2022

AbstractSome early antimalarial drugs have been repurposed for experimental applications, thus extending their utility well beyond the point when resistance becomes prevalent in circulating parasite populations. One such drug is sulfadiazine, which is an analog of p-aminobenzoic acid (pABA), and acts as a competitive inhibitor of dihydropteroate synthase, which is an essential enzyme in the parasite’s folate synthesis pathway that is required for DNA synthesis. Sulfadiazine treatment of mice infected with P. yoelii and P. berghei is routinely used to enrich for gametocytes by killing asexual blood stage parasites, but it is not well known if the exposed gametocytes are perturbed or if there is a detrimental effect on transmission. To determine if there was a significant effect of sulfadiazine exposure upon host-to-vector transmission, we transmitted Plasmodium yoelii (17XNL strain) parasites to Anopheles stephensi mosquitoes and evaluated the prevalence of infection (percent of mosquitoes infected) and intensity of infection (number of oocysts per infected mosquito) under different sulfadiazine treatment conditions of the mouse or of the mosquitoes. We observed that parasites exposed to sulfadiazine either in the mouse host or in the mosquito vector had a reduction in both the number of mosquitoes that became infected and in the intensity of infection compared to untreated controls. We also observed that provision of freshly prepared pABA in the mosquito sugar water could only marginally overcome the defects caused by sulfadiazine treatment. In contrast, we determined that gametocytes exposed to sulfadiazine were able to be fertilized and develop into morphologically mature ookinetes in vitro, and thus that sulfadiazine exposure in the host may be reversible if the drug is washed out and the parasites are supplemented with pABA in the culture media. Overall, this indicates that sulfadiazine dampens host-to-vector transmission, and that this inhibition can only be partially overcome by exposure to fresh pABA in vivo and in vitro. Because gametocytes are of great interest for developing transmission blocking interventions, we recommend that less disruptive approaches for gametocyte enrichment be used in order to study minimally perturbed parasites.
cGAS recruitment to micronuclei is dictated by pre-existing nuclear chromatin status
Authors: MacDonald Kate M. , Nicholson-Puthenveedu Shirony , Tageldein Maha M. , Arrowsmith Cheryl , Harding Shane M. 
Published: January 2022

SUMMARYMicronuclei (MN) are aberrant cytosolic compartments containing broken genomic fragments or whole lagging chromosomes. MN envelopes irreversibly rupture, allowing the viral receptor cGAS to localize to MN and initiate an inflammatory signalling cascade. Here, we demonstrate that MN envelope rupture is not sufficient for cGAS localization. Unlike MN that arise following ionizing radiation (IR), ruptured MN generated from acute transcription stressors DRB or siSRSF1 are refractory to cGAS localization. Recruitment of cGAS to MN is blocked by inhibiting the histone methyltransferase DOT1L prior to IR exposure, demonstrating that cGAS recruitment to MN is dictated by nuclear chromatin organization at the time of DNA damage. Loss of cGAS+ MN, caused either by acute transcription stressors or by preventing DOT1L-deposited histone methylation, corresponded to significantly decreased cGAS-dependent inflammatory signalling. These results implicate nuclear chromatin organization in micronuclear composition and activity, influencing the ability of damage-induced MN to retain cytosolic proteins upon rupture.
Von Willebrand factor A1 domain affinity for GPIbα and stability are differentially regulated by its O-glycosylated N-linker and C-linker
Authors: Bonazza Klaus , Iacob Roxana E. , Hudson Nathan E. , Li Jing , Lu Chafen , Engen John R. , Springer Timothy A. 
Published: January 2022

AbstractHemostasis in the arterial circulation is mediated by binding of the A1 domain of the ultralong protein von Willebrand factor to GPIbα on platelets to form a platelet plug. A1 is activated by tensile force on VWF concatemers imparted by hydrodynamic drag force. The A1 core is protected from force-induced unfolding by a long-range disulfide that links cysteines near its N and C-termini. The O-glycosylated linkers between A1 and its neighboring domains, which transmit tensile force to A1, are reported to regulate A1 activation for binding to GPIb, but the mechanism is controversial and incompletely defined. Here, we study how these linkers, and their polypeptide and O-glycan moieties, regulate A1 affinity by measuring affinity, kinetics, thermodynamics, hydrogen deuterium exchange (HDX), and unfolding by temperature and urea. The N-linker lowers A1 affinity 40-fold with a stronger contribution from its O-glycan than polypeptide moiety. The N-linker also decreases HDX in specific regions of A1 and increases thermal stability and the energy gap between its native state and an intermediate state, which is observed in urea-induced unfolding. The C-linker also decreases affinity of A1 for GPIbα, but in contrast to the N-linker, has no significant effect on HDX or A1 stability. Among different models for A1 activation, our data are consistent with the model that the intermediate state has high affinity for GPIbα, which is induced by tensile force physiologically and regulated allosterically by the N-linker.Impact StatementBoth the polypeptide and attached O-glycans N-terminal to the A1 domain in von Willebrand factor lower its affinity for its ligand GPIbα on platelets, its stability, and structural dynamics and decrease population of a high-affinity, intermediate state in unfolding.Key pointsLigand-binding affinity of A1 and the stability of its native state is regulated by an N-terminal interdomain, O-glycosylated linker
Detailed measurements and simulations of electric field distribution of two TMS coils cleared for obsessive compulsive disorder in the brain and in specific regions associated with OCD
Authors: Tzirini Marietta , Roth Yiftach , Harmelech Tal , Zibman Samuel , Pell Gaby S , Kimiskidis Vasilios k. , Tendler Aron , Zangen Abraham , Samaras Theodoros 
Published: January 2022

AbstractThe FDA cleared deep transcranial magnetic stimulation (Deep TMS) with the H7 coil for obsessive-compulsive disorder (OCD) treatment, following a double-blinded placebo-controlled multicenter trial. Two years later the FDA cleared TMS with the D-B80 coil on the basis of substantial equivalence. In order to investigate the induced electric field characteristics of the two coils, these were placed at the treatment position for OCD over the prefrontal cortex of a head phantom, and the field distribution was measured. Additionally, numerical simulations were performed in eight Population Head Model repository models with two sets of conductivity values and three Virtual Population anatomical head models and their homogeneous versions. The H7 was found to induce significantly higher maximal electric fields (p<0.0001, t=11.08) and to stimulate two to five times larger volumes in the brain (p<0.0001, t=6.71). The rate of decay of electric field with distance is significantly slower for the H7 coil (p < 0.0001, Wilcoxon matched-pairs test). The field at the scalp is 306% of the field at a 3 cm depth with the D-B80, and 155% with the H7 coil. The H7 induces significantly higher intensities in broader volumes within the brain and in specific brain regions known to be implicated in OCD (dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus (IFG), orbitofrontal cortex (OFC) and pre-supplementary motor area (pre-SMA)) compared to the D-B80. Significant field ≥ 80 V/m is induced by the H7 (D-B80) in 15% (1%) of the dACC, 78% (29%) of the pre-SMA, 50% (20%) of the dlPFC, 30% (12%) of the OFC and 15% (1%) of the IFG. Considering the substantial differences between the two coils, the clinical efficacy in OCD should be tested and verified separately for each coil.
Lateral entorhinal cortex inputs modulate hippocampal dendritic excitability by recruiting a local disinhibitory microcircuit
Authors: Bilash Olesia M. , Chavlis Spyridon , Poirazi Panayiota , Basu Jayeeta 
Published: January 2022

ABSTRACTThe lateral entorhinal cortex (LEC) provides information about multi-sensory environmental cues to the hippocampus through direct inputs to the distal dendrites of CA1 pyramidal neurons. A growing body of work suggests that LEC neurons perform important functions for episodic memory processing, coding for contextually-salient elements of an environment or the experience within it. However, we know little about the functional circuit interactions between LEC and the hippocampus. In this study, we combine functional circuit mapping and computational modeling to examine how long-range glutamatergic LEC projections modulate compartment-specific excitation-inhibition dynamics in hippocampal area CA1. We demonstrate that glutamatergic LEC inputs can drive local dendritic spikes in CA1 pyramidal neurons, aided by the recruitment of a disinhibitory vasoactive intestinal peptide (VIP)-expressing inhibitory neuron microcircuit. Our circuit mapping further reveals that, in parallel, LEC also recruits cholecystokinin (CCK)-expressing inhibitory neurons, which our model predicts act as a strong suppressor of dendritic spikes. These results provide new insight into a cortically-driven GABAergic microcircuit mechanism that gates non-linear dendritic computations, which may support compartment-specific coding of multi-sensory contextual features within the hippocampus.HIGHLIGHTSSlice electrophysiology experiments investigate how lateral entorhinal cortex influences hippocampal area CA1LEC drives local spikes in distal dendrites but not in somata of CA1 pyramidal neuronsLEC inputs recruit VIP IN and CCK IN populations in CA1, but not SST INsComputational modeling and circuit manipulation experiments identify a VIP IN-mediated disinhibitory microcircuit for gating local dendritic spike generationIN BRIEFBilash et al. found that a distal cortical input is capable of driving local dendritic spikes in hippocampal pyramidal neurons. This dendritic spike generation is promoted by cortical recruitment of a local VIP interneuron-mediated disinhibitory microcircuit. Their results highlight new circuit mechanisms by which dynamic interaction of excitation, inhibition, and disinhibition support supralinear single-cell computations.