bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nosocomial RSV-related in-hospital mortality in children <5 years: a global case series
Authors: Löwensteyn Yvette N. , Willemsen Joukje E. , Mazur Natalie I. , Scheltema Nienke M. , van Haastregt Nynke C. J. , Buuren Amber ten , van Roessel Ichelle , Scheepmaker Dunja , Nair Harish , van de Ven Peter M. , Bont Louis J. ,   RSV GOLD study group
Published: January 2022

ABSTRACTBackgroundAccording to the World Health Organization the global burden of nosocomial infections is poorly characterized as surveillance systems for nosocomial infection are lacking. Nosocomial infections occur at higher rates in low- and lower-middle-income countries (LMICs) than in high-income countries (HICs). Current global RSV burden estimates are largely based on community-acquired disease. We aimed to characterize children with nosocomial RSV-related mortality and to understand the potential impact of RSV immunization strategies.MethodsRSV GOLD is a global registry of children younger than 5 years who died with laboratory-confirmed RSV infection. We compared clinical and demographic characteristics of children with nosocomial and community-acquired RSV in-hospital mortality.ResultsWe included 231 nosocomial and 931 community-acquired RSV-related in-hospital deaths from 65 countries. Median age at death was similar for both groups (5.4 vs 6 months). As expected, a higher proportion of children with nosocomial infection had comorbidities (87% vs 57%; p<0.001) or was born preterm (46% vs 24%; p<0.001) than children with community-acquired infection. The proportion of nosocomial deaths among all RSV deaths was lower in LMICs than in upper-middle-income countries (UMICs) and HICs (12% vs 18% and 26%, respectively).ConclusionsThis is the first global case series of children dying with nosocomial RSV infection. Future infant-targeted immunization strategies can prevent the majority of nosocomial RSV-related deaths. Although nosocomial RSV deaths are expected to occur at highest rates in LMICs, the number of reported nosocomial RSV deaths was low in these countries. Hospital-based surveillance is needed to capture the full burden of nosocomial RSV mortality in LMICs.Key pointsThe proportion of reported nosocomial RSV-related deaths is substantially lower in lower-middle-income countries than in upper-middle-income countries and high-income countries (12% vs 18% and 26%, respectively).The majority of nosocomial RSV-related deaths can be prevented by infant-targeted immunization strategies as more than half were younger than 6 months of age.
Local interactions between steady-state visually evoked potentials at nearby flickering frequencies
Authors: Liza Kumari , Ray Supratim 
Published: January 2022

AbstractSteady-state visually evoked potentials (SSVEP) are widely used to index top-down cognitive processing in human electroencephalogram (EEG) studies. Typically, two stimuli flickering at different temporal frequencies (TFs) are presented, each producing a distinct response in the EEG at its flicker frequency. However, how SSVEP responses in EEG are modulated in the presence of a competing flickering stimulus just due to sensory interactions is not well understood. We have previously shown in local field potentials (LFP) recorded from awake monkeys that when two overlapping full screen gratings are counter-phased at different TFs, there is an asymmetric SSVEP response suppression, with greater suppression from lower TFs, which further depends on the relative orientations of the gratings (stronger suppression and asymmetry for parallel compared to orthogonal gratings). Here, we first confirmed these effects in both male and female human EEG recordings. Then, we mapped the response suppression of one stimulus (target) by a competing stimulus (mask) over a much wider range than the previous study. Surprisingly, we found that the suppression was not stronger at low frequencies in general, but systematically varied depending on the target TF, indicating local interactions between the two competing stimuli. These results were confirmed in both human EEG and monkey LFP and electrocorticogram (ECoG) data. Our results show that sensory interactions between multiple SSVEPs are more complex than shown previously and are influenced by both local and global factors, underscoring the need to cautiously interpret the results of studies involving SSVEP paradigms.
Establishment of a hypoxia ischemia reperfusion brain damage model in neonatal rats
Authors: Fu Xiaoqin , Zhang Tianlei , Lin Wei , Jiao Mengdie , Zhang Zhiwei , Geng Jiayi , Wei Qing , Qi Ailin , Kexin Lin , Zheng Yi hui , Fang Mingchu , Li Peijun , Lin Zhenlang 
Published: January 2022

AbstractObjectiveRice-Vannucci model has been widely used as HIE (Hypoxic ischemic encephalopathy) animal model in the past forty years, but it does not mimic reperfusion injury that occurs during HIE. The aim of the present study was to establish a new neonatal rat model by simulating hypoxia ischemia reperfusion brain damage (HIRBD) through “common carotid artery (CCA) muscle bridge”.MethodsSixty 7-day-old male Sprague-Dawley rats were randomly assigned to group A (HIRBD groups, n=36), group B (Rice-Vannucci group, n=12), and group C (sham-operated group, n=12). Rats in group A were assigned to 3 subgroups (A1-A3, 12 animals/subgroup). Dynamic changes in cerebral blood flow (CBF) were evaluated by the laser speckle imaging system. The status of the CCA was observed under a stereomicroscope. Changes in body weight, gross morphology as well as pathological sections of brain tissue were examined to evaluate the feasibility of the model.ResultsThe results indicated that CCA muscle bridge successfully blocked the CBF. CBF was restored after removal of the CCA muscle bridge in HIRBD groups. The CCA was in good condition after removing the muscle bridge, and blood supply was not affected. Changes in body weight, gross morphology and pathological sections of brain tissue indicated that ischemia reperfusion induced by the CCA muscle bridge method caused varying degrees of brain damage.ConclusionCCA muscle bridge method is effective for establishing a reliable, stable, and reproducible neonatal rat model for study of HIRBD.
Humanized CYP2C19 transgenic mouse as an animal model of cerebellar ataxia
Authors: Milosavljević Filip , Brusini Irene , Atanasov Andrea , Manojlović Marina , Novalen Maria , Vučić Marija , Dušić Zorana Oreščanin , Brkljačić Jelena , Miksys Sharon , Miljević Čedo , Nikolić Aleksandra , Blagojević Duško , Wang Chunliang , Damberg Peter , Pešić Vesna , Tyndale Rachel F , Ingelman-Sundberg Magnus , Jukić Marin M 
Published: January 2022

ABSTRACTBackgroundAnimal models are essential for understanding etiology and pathophysiology of movement disorders. Previously, we have found that mice transgenic for the human CYP2C19 gene, expressed in the liver and developing brain, exhibit altered neurodevelopment associated with impairments of their motor function and emotionality.ObjectivesTo characterize motoric phenotype of the CYP2C19 transgenic mice and validate its usefulness as an animal model of ataxia.MethodsThe rotarod and beam-walking tests were utilized to quantify the functional alterations induced by motoric phenotype. Dopaminergic system was assessed by tyrosine hydroxylase immunohistochemistry and by chromatographic quantification of the whole-brain dopamine levels. Beam-walking test was also repeated after the treatment with the dopamine receptor antagonists, ecopipam and raclopride. The volumes of 20 brain regions in the CYP2C19 transgenic mice and controls were quantified by 9.4T gadolinium-enhanced postmortem structural neuroimaging.ResultsCYP2C19 transgenic mice were found to exhibit abnormal, unilateral ataxia-like gait, clasping reflex and 5.6-fold more paw-slips using the beam-walking test (p<0.0001, n=89); the phenotype was more pronounced in younger animals. Hyperdopaminergism was observed in the CYP2C19 mice; however, the motoric impairment was not ameliorated by dopamine receptor antagonists and there was also no midbrain dopamine neuron loss in CYP2C19 mice. However, in these mice, cerebellar volume was drastically decreased (11.8% [95%CI: −14.7, −9.0], q<0.0001, n=59), whereas a moderate decrease in hippocampal volume was observed (−4.2% [95%CI: −6.4%, −1.9%], q=0.015, n=59).ConclusionsHumanized CYP2C19 transgenic mice exhibit altered motoric function and functional motoric impairments; this phenotype is likely caused by an aberrant cerebellar development.
A striatal plasticity that supports the long-term preservation of motor function in Parkinsonian mice
Authors: Brague Joe C. , Seal Rebecca P. 
Published: January 2022

SUMMARYMotor deficits of Parkinson’s disease (PD) such as rigidity, bradykinesia and akinesia result from a progressive loss of nigrostriatal dopamine neurons. No therapies exist that slow their degeneration and the most effective treatments for the motor symptoms: L-dopa -the precursor to dopamine, and deep brain stimulation can produce dyskinesias and are highly invasive, respectively. Hence, alternative strategies targeted to slow the progression or delay the onset of motor symptoms are still highly sought. Here we report the identification of a long-term striatal plasticity mechanism that delays for several months, the onset of motor deficits in a mouse PD model. Specifically, we show that a one-week transient daily elevation of midbrain dopamine neuron activity during depletion preserves the connectivity of direct but not indirect pathway projection neurons. The findings are consistent with the balance theory of striatal output pathways and suggest a novel approach for treating the motor symptoms of PD.
Alignment of spatial genomics and histology data using deep Gaussian processes
Authors: Jones Andrew , Townes F. William , Li Didong , Engelhardt Barbara E. 
Published: January 2022

AbstractSpatially-resolved genomic technologies have allowed us to study the physical organization of cells and tissues, and promise an understanding of the local interactions between cells. However, it remains difficult to precisely align spatial observations across slices, samples, scales, individuals, and technologies. Here, we propose a probabilistic model that aligns a set of spatially-resolved genomics and histology slices onto a known or unknown common coordinate system into which the samples are aligned both spatially and in terms of the phenotypic readouts (e.g., gene or protein expression levels, cell density, open chromatin regions). Our method consists of a two-layer Gaussian process: the first layer maps the observed samples’ spatial locations into a common coordinate system, and the second layer maps from the common coordinate system to the observed readouts. Our approach also allows for slices to be mapped to a known template coordinate space if one exists. We show that our registration approach enables complex downstream spatially-aware analyses of spatial genomics data at multiple resolutions that are impossible or inaccurate with unaligned data, including an analysis of variance, differential expression across the z-axis, and association tests across multiple data modalities.
Escherichia coli YigI is a conserved ɣ-proteobacterial acyl-CoA thioesterase permitting metabolism of unusual fatty acid substrates
Authors: Schmidt Michael , Proctor Theresa , Diao Rucheng , Freddolino Peter L. 
Published: January 2022

AbstractThioesterases play a critical role in metabolism, membrane biosynthesis, and overall homeostasis for all domains of life. In this present study, we characterize a putative thioesterase from Escherichia coli MG1655 and define its role as a cytosolic enzyme. Building on structure-guided functional predictions, we show that YigI is a medium- to -long chain acyl-CoA thioesterase that is involved in the degradation of conjugated linoleic acid (CLA) in vivo, showing overlapping specificity with two previously defined E. coli thioesterases TesB and FadM. We then bioinformatically identify the regulatory relationships that induce YigI expression, which include: an acidic environment, high oxygen availability, and exposure to aminoglycosides. Our findings define a role for YigI and shed light on why the E. coli genome harbors numerous thioesterases with closely related functions.ImportancePrevious research has shown that long chain acyl-CoA thioesterases are needed for E. coli to grow in the presence of carbon sources such as conjugated linoleic acid, but that E. coli must possess at least one such enzyme that had not previously been characterized. Building off of structure-guided function predictions, we showed that the poorly annotated protein YigI is indeed the previously unidentified third acyl CoA thioesterase. We found that the three potentially overlapping acyl-CoA thioesterases appear to be induced by non-overlapping conditions, and use that information as a starting point for identifying the precise functions catalyzed by each such thioesterase, which is an important prerequisite for their industrial application and for more accurate metabolic modeling of E. coli.
Sensitization of Chrysosplenetin against Artemisinin Resistant Plasmodium berghei K173 via Blocking Host ABC Transporters Potentially Mediated by NF-κB p52 or PXR/CAR Signaling Pathway
Authors: Zhao Xuesong , Ni Shanhong , Zhang Yuanyuan , Wu Xiuli , Yao Ying , Chen Jing 
Published: January 2022

ABSTRACTThis study investigated if artemisinin-chrysosplenetin combination (ART-CHR) improved ART antimalarial efficacy against resistant Plasmodium berghei K173 via depressing host ABC transporter and potential molecular mechanism. Parasitaemia% and inhibition% were calculated and gene/protein expressions of ABC transporters or PXR/CAR/NF-κB p52 were detected by Western-blot and RT-qPCR. In vitro transcription of PXR/CAR was studied by dual-luciferase reporter assay. Our data indicated that ART-CHR improved ART efficacy against resistant parasites. P-gp inhibitor verapamil and CHR showed a stronger effect in killing resistant parasites while vehicle and Bcrp inhibitor novobiocin did not. ART activated intestinal ABCB1/ABCG2 and CHR inhibited them. ART decreased Bcrp protein whereas CHR increased it. ART ascended ABCC1/ABCC4/ABCC5 mRNA but ART-CHR descended them. CHR as well as rifampin (RIF) or 5-fluorouracil (5-FU) increased transcription levels of PXR/CAR while showed a versatile regulation on in vivo hepatic and enternal PXR/CAR in Mdr1a+/+ (WT) or Mdr1a-/- (KO) mice infected with sensitive or resistant parasites. Oppositely, hepatic and enteric N-κB p52 mRNA was conformably decreased in WT but increased in KO-resistant mice. NF-κB pathway should potentially involved in the mechanism of CHR on inhibiting ABC transporters and ART resistance while PXR/CAR play a more complicated role in this mechanism.
Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection
Authors: Packer RJ , Shrine N , Hall R , Melbourne CA , Thompson R , Williams AT , Paynton ML , Guyatt AL , Lee PH , John C , Campbell A , Hayward C , de Vries M , Vonk JM , Davitte J , Hessel E , Michalovich D , Betts JC , Sayers I , Yeo A , Hall IP , Tobin MD , Wain LV 
Published: January 2022

AbstractBackgroundChronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment.MethodsWe conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (P<5×10−8) were investigated in additional independent studies, were fine-mapped, and putative causal genes identified by gene expression analysis. GWAS of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease amongst the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWAS).FindingsFrom a GWAS of 9,714 cases and 48,471 controls, we identified six novel genome-wide significant signals for chronic sputum production including signals in the Human Leukocyte Antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and the FUT2 locus. The four common variant associations were supported by independent studies with a combined sample size of up to 2,203 cases and 17,627 controls. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino-acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations.InterpretationNovel signals at the FUT2 and mucin loci highlight mucin fucosylation as a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.
Developmental origins of cell heterogeneity in the human lung
Authors: Sountoulidis Alexandros , Salas Sergio Marco , Braun Emelie , Avenel Christophe , Bergenstråhle Joseph , Vicari Marco , Czarnewski Paulo , Theelke Jonas , Liontos Andreas , Abalo Xesus , Andrusivová Žaneta , Asp Michaela , Li Xiaofei , Hu Lijuan , Sariyar Sanem , Casals Anna Martinez , Ayoglu Burcu , Firsova Alexandra , Michaëlsson Jakob , Lundberg Emma , Wählby Carolina , Sundström Erik , Linnarsson Sten , Lundeberg Joakim , Nilsson Mats , Samakovlis Christos 
Published: January 2022

SummaryThe lung contains numerous specialized cell-types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a first comprehensive topographic atlas of early human lung development. We report 83 cell states, several spatially-resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated scRNA-Seq and spatial transcriptomics into a web-based, open platform for interactive exploration. To illustrate the utility of our approach we show distinct states of secretory and neuroendocrine cells, largely overlapping with the programs activated either during lung fibrosis or small cell lung cancer progression. We define the origin of uncharacterized airway fibroblasts associated with airway smooth muscle in bronchovascular bundles, and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.
Circadian and diel regulation of photosynthesis in the bryophyte Marchantia polymorpha
Authors: Cuitun-Coronado David , Rees Hannah , Colmer Joshua , Hall Anthony , de Barros Dantas Luíza Lane , Dodd Antony N. 
Published: January 2022

AbstractCircadian rhythms are 24-hour biological cycles that align metabolism, physiology and development with daily environmental fluctuations. Photosynthetic processes are governed by the circadian clock in both flowering plants and some cyanobacteria, but it is unclear how extensively this is conserved throughout the green lineage. We investigated the contribution of circadian regulation to aspects of photosynthesis in Marchantia polymorpha, a liverwort that diverged from flowering plants early in the evolution of land plants. First, we identified in M. polymorpha the circadian regulation of photosynthetic biochemistry, measured using two approaches (delayed fluorescence, PAM fluorescence). Second, we identified that light-dark cycles synchronize the phase of 24 h cycles of photosynthesis in M. polymorpha, whereas the phases of different thalli desynchronize under free running conditions. This might also be due to masking of the underlying circadian rhythms of photosynthesis by light-dark cycles. Finally, we used a pharmacological approach to identify that chloroplast translation might be necessary for clock control of light harvesting in M. polymorpha. We infer that the circadian regulation of photosynthesis are well-conserved amongst terrestrial plants.
Multidimensional cerebellar computations for flexible kinematic control of movements
Authors: Markanday Akshay , Hong Sungho , Inoue Junya , Schutter Erik De , Thier Peter 
Published: January 2022

AbstractBoth the environment and our body keep changing dynamically. Hence, ensuring movement precision requires adaptation to multiple demands occurring simultaneously. Here we show that the cerebellum performs the necessary multi-dimensional computations for the flexible control of different movement parameters depending on the prevailing context. This conclusion is based on the identification of a manifold-like activity in both mossy fibers (MF, network input) and Purkinje cells (PC, output), recorded from monkeys performing a saccade task. Unlike MFs, the properties of PC manifolds developed selective representations of individual movement parameters. Error feedback-driven climbing fiber input modulated the PC manifolds to predict specific, error type-dependent changes in subsequent actions. Furthermore, a feed-forward network model that simulated MF-to-PC transformations revealed that amplification and restructuring of the lesser variability in the MF activity is a pivotal circuit mechanism. Therefore, flexible control of movement by the cerebellum crucially depends on its capacity for multi-dimensional computations.
The phylogenomic landscape of the genus Serratia
Authors: Williams David J. , Grimont Patrick A. D. , Cazares Adrián , Grimont Francine , Ageron Elisabeth , Pettigrew Kerry A. , Cazares Daniel , Njamkepo Elisabeth , Weill François-Xavier , Heinz Eva , Holden Matthew T. G. , Thomson Nicholas R. , Coulthurst Sarah J. 
Published: January 2022

AbstractThe genus Serratia has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We show that Serratia is a diverse genus which displays striking plasticity and ability to adapt to its environment, including a highly-varied portfolio of plasmids, and provide evidence of different patterns of gene flow across the genus. This work provides an essential platform for understanding the emergence of clinical and other lineages of Serratia.
OverFlap PCR – a reliable approach for generation of plasmid DNA libraries containing random sequences without template bias
Authors: Linars Artis , Silamikelis Ivars , Gudra Dita , Roga Ance , Fridmanis Davids 
Published: January 2022

ABSTRACTOver the decades the improvement of naturally occurring proteins and creation of novel ones has been the primary goal for many practical biotechnology researchers and it is widely recognized that randomization of protein sequences coupled to various effect screening methodologies is one of the most powerful techniques for fast, efficient and purposeful approach for acquisition of desired improvements. Over the years considerable advancements have been made in this field, however development of PCR based or template guided methodologies has been hampered by the resulting template sequence bias. In this article we present novel whole plasmid amplification based approach, which we named OverFlap PCR, for randomization of virtually any region of the plasmid DNA, without introduction of mentioned bias.