bluuebunny/crossref_metadata_2025_split huggingface dataset:
Number and proportion of P.falciparumgametocytes vary from acute infection to chronic parasite carriage despite unaltered sexual commitment rate
Authors: van Dijk Hannah , Kampmann Martin , Lima Nathalia F , Gabel Michael , Dabbas Usama , Doumbo Safiatou , Cisse Hamidou , Li Shanping , Jeninga Myriam , Thomson-Luque Richard , Doumtabe Didier , Petter Michaela , Kayentao Kassoum , Ongoiba Aissata , Bousema Teun , Crompton Peter D , Traore Boubacar , Graw Frederik , Portugal Silvia 
Published: November 2021

AbstractPlasmodium falciparuminfections persist through long dry seasons at low parasitaemia without causing malaria symptoms and thus remain untreated. In asymptomatic children, increased circulation of infected erythrocytes without adhering to the vascular endothelium is observed during the dry months, compared to febrile malaria in the wet season. However, alterations of parasite sexual commitment and gametocytogenesis have not been investigated. Here, we compared the expression of genes related to sexual commitment and gametocytogenesis, the proportion and density ofP. falciparumgametocytes, and the blood concentration of phospholipids in dry season asymptomatic individuals versus symptomatic subjects in the wet season. Additionally, we adapted a within-host mathematical model considering asexual and sexually-committed parasites and gametocytes to understand the dynamics of gametocyte number and proportion as infections progress. Compared to clinical malaria cases, transcripts of late-stage gametocytes were predominantly upregulated in the dry season, associating with increased proportions of mature gametocytes; while transcription of genes related to parasite sexual commitment was unaltered throughout the year. Our data suggest that gametocyte density and proportion diverge as infections progress from recent transmission to chronic carriage, without alterations in the sexual commitment rate over time.
Design, construction and optimization of a synthetic RNA polymerase operon in Escherichia coli
Authors: Houkes Joep , Olivi Lorenzo , Paquet Zacharie , Claassens Nico J. , van der Oost John 
Published: November 2021

ABSTRACTProkaryotic genes encoding functionally related proteins are often clustered in operons. The compact structure of operons allows for co-transcription of the genes, and for co-translation of the polycistronic messenger RNA to the corresponding proteins. This leads to reduced regulatory complexity and enhanced gene expression efficiency, and as such to an overall metabolic benefit for the protein production process in bacteria and archaea. Interestingly, the genes encoding the subunits of one of the most conserved and ubiquitous protein complexes, the RNA polymerase, are not clustered in a single operon. Rather, its genes are scattered in all known prokaryotic genomes, generally integrated in different ribosomal operons. To analyze the impact of this genetic organization on the fitness of Escherichia coli, we constructed a bacterial artificial chromosome harboring the genes encoding the RNA polymerase complex in a single operon. Subsequent deletion of the native chromosomal genes led to a reduced growth on minimal medium. However, by using adaptive laboratory evolution the growth rate was restored to wild-type level. Hence, we show that a highly conserved genetic organization of core genes in a bacterium can be reorganized by a combination of design, construction and optimization, yielding a well-functioning synthetic genetic architecture.
Discovery of imidazole-based inhibitors of P. falciparum cGMP-dependent protein kinase
Authors: Yadav Bheemanaboina Rammohan R. , de Souza Mariana Laureano , Gonzalez Mariana Lozano , Mahmood Shams Ul , Eck Tyler , Kreiss Tamara , Aylor Samantha O. , Roth Alison , Lee Patricia , Pybus Brandon S. , Colussi Dennis J. , Childers Wayne E. , Gordon John , Siekierka John J. , Bhanot Purnima , Rotella David P. 
Published: November 2021

ABSTRACTThe discovery of new targets for treatment of malaria and in particular those aimed at the pre-erythrocytic stage in the life cycle, advanced with the demonstration that orally administered inhibitors of Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) could clear infection in a murine model. This enthusiasm was tempered by unsatisfactory safety and/or pharmacokinetic issues found with these chemotypes. To address the urgent need for new scaffolds, this manuscript presents initial structure-activity relationships in an imidazole scaffold at four positions, representative in vitro ADME, hERG characterization and cell-based anti-parasitic activity. This series of PfPKG inhibitors has good in vitro PfPKG potency, low hERG activity and cell-based anti-parasitic activity against multiple Plasmodium species that appears to correlate with in vitro potency.
MiRNA and Erythropoietin profiles during the menstrual cycle in relation to hematological and lipid biomarkers
Authors: Bergström Helena , Heiland Carmel , Björkhem-Bergman Linda , Ekström Lena 
Published: November 2021

AbstractBackgroundCirculatory micro RNAs (miRNA) have been discussed as complementary diagnostic markers in cardiovascular diseases, and in anti-doping testing. MiR-144 and miR-486 have been associated with cholesterol homeostasis and hematopoiesis, respectively. In addition, they have been suggested as putative biomarkers for autologous blood transfusion and erythropoietin (EPO) doping. The aim of the present study was to assess the variability of miR-144-3p/5p, miR-486-5p/3p and EPO during the menstrual cycle. Secondary aim was to study the correlations between miRNAs, EPO and hematological parameters and lipids.Methods13 healthy women with regular menses were followed with weekly blood sampling during two whole menstrual cycles. MiRNAs were analyzed using TaqMan and PCR followed by calculation of the relative expression for each miRNA using ddCT approach.ResultsThere was no menstrual cycle variability in miRNAs and EPO. MiRNA-144-3p was associated with HDL-C (rs=-0.34, p=0.036) and miRNA-486-5p with Hb (rs=0.32, p=0.046). EPO concentrations correlated to lymphocytes (rs=-0.062, p=0.0002)),Hb (rs= -0.42, p=0.0091), HDL-C (rs=0.36, p=0.030) and triglycerides (rs=-0.54, p=0.0006).ConclusionsThe results of this study may increase the understanding of how miR486-5p and miR144-3p as well as EPO correlate to hematopoietic and lipid biomarkers.
Identification and characterization of BEND2 as a novel and key regulator of meiosis during mouse spermatogenesis
Authors: Ma Longfei , Xie Dan , Lin Xiwen , Nie Hengyu , Chen Jian , Gao Chenxu , Duo Shuguang , Han Chunsheng 
Published: November 2021

AbstractThe chromatin state undergoes global and dynamic changes during spermatogenesis, and is critical to chromosomal synapsis, meiotic recombination, and transcriptional regulation. However, the key regulators involved and the underlying molecular mechanisms remain poorly understood. Herein we report that mouse BEND2, one of the BEN-domain-containing proteins conserved in vertebrates, was specifically expressed in spermatogenic cells within a short time-window spanning meiotic initiation, and that it plays an essential role in the progression of prophase in meiosis I. Bend2 gene knockout in male mice arrested meiosis at the transition from zygonema to pachynema, disrupted synapsis and DNA double-strand break repair, and induced non-homologous chromosomal pairing. BEND2 interacted with a number of chromatin-associated proteins—including ZMYM2, LSD1, CHD4, and ADNP— which are components of certain transcription-repressor complexes. BEND2-binding sites were identified in diverse chromatin states and enriched in simple sequence repeats. BEND2 contributed to shutting down the mitotic gene-expression program and to the activation of meiotic and post-meiotic gene expression, and it regulated chromatin accessibility as well as the modification of H3K4me3. Therefore, our study identified BEND2 as a novel and key regulator of meiosis, gene expression, and chromatin state during mouse spermatogenesis.TeaserMeiosis is a highly complex yet poorly understood process that involves the concerted actions of an increasing number of regulators, of which the list remains incomplete. Ma et al. identified BEND2 as a novel and key regulator of meiosis and showed that it interacts with critical chromatin modulators and specific genomic elements to control the expression of mitotic and meiotic genes.
Factors Influencing the Detection of Antibacterial Resistant Escherichia coli in Faecal Samples from Individual Cattle
Authors: Turner Andrea , Schubert Hannah , Puddy Emma F. , Sealey Jordan E. , Gould Virginia C. , Cogan Tristan A. , Avison Matthew B. , Reyher Kristen K. 
Published: November 2021

AbstractAimsTo investigate whether on-farm antibacterial usage (ABU), environmental antibacterial resistant (ABR) Escherichia coli prevalence, and sampling and sample handling methodologies are associated with ABR E. coli positivity in individual faecal samples from dairy heifers.Methods and ResultsThree hundred and sixty-four heifers from 37 farms were sampled via rectal or faecal pat sampling. Samples were stored at -80°C for variable periods before microbiological analysis. Data analysis was through a multilevel, multivariable logistic regression approach.Individual rectal samples had increased odds of positivity for amoxicillin, cefalexin and tetracycline-resistant E. coli. Sample storage for 6-12 month was associated with decreased odds of finding amoxicillin and tetracycline-resistant E. coli. On-farm ABU had little influence, and environmental ABR E. coli prevalence had no significant influence on on the odds of sample-level positivity for ABR E. coli.ConclusionsSampling methodology and sample handling have a greater association than on-farm factors with the detection of ABR E. coli in individual faecal samples from dairy heifers.Significance and Impact of the StudySampling and storage methodologies should be considered carefully at the point of designing ABR surveillance studies in livestock and their environments and, where possible, standardised between and within future studies.
Predictive processing of scene layout depends on naturalistic depth of field
Authors: Gandolfo Marco , Nägele Hendrik , Peelen Marius V. 
Published: November 2021

AbstractBoundary extension (BE) is a classic memory illusion in which observers remember more of a scene than was presented. According to predictive processing accounts, BE reflects the integration of visual input and expectations of what is beyond a scene’s boundaries. According to normalization accounts, BE rather reflects one end of a normalization process towards a scene’s typically-experienced viewing distance, such that close-up views give BE but distant views give boundary contraction. Here across four experiments, we show that BE strongly depends on depth-of-field (DOF), as determined by the aperture settings on a camera. Photographs with naturalistic DOF led to larger BE than photographs with unnaturalistic DOF, even when showing distant views. We propose that BE reflects a predictive mechanism with adaptive value that is strongest for naturalistic views of scenes. The current findings indicate that DOF is an important variable to consider in the study of scene perception and memory.Statement of RelevanceIn daily life, we experience a rich and continuous visual world in spite of the capacity limits of the visual system. We may compensate for such limits with our memory, by filling-in the visual input with anticipatory representations of upcoming views. The boundary extension illusion (BE) provides a tool to investigate this phenomenon. For example, not all images equally lead to BE. In this set of studies, we show that memory extrapolation beyond scene boundaries is strongest for images resembling human visual experience, showing depth-of-field in the range of human vision. Based on these findings, we propose that predicting upcoming views is conditional to a scene being perceived as naturalistic. More generally, the strong reliance of a cognitive effect, such as BE, on naturalistic image properties indicates that it is imperative to use image sets that are ecologically-representative when studying the cognitive, computational, and neural mechanisms of scene processing.
Correcting Cardiorespiratory Noise in Resting-state Functional MRI Data Acquired in Critically Ill Patients
Authors: Chan Suk-tak , Sanders William R. , Fischer David , Kirsch John E. , Napadow Vitaly , Bodien Yelena G. , Edlow Brian L. 
Published: November 2021

AbstractResting-state functional MRI (rs-fMRI) is being used to develop diagnostic, prognostic, and therapeutic biomarkers for critically ill patients with severe brain injuries. In studies of healthy volunteers and non-critically ill patients, prospective cardiorespiratory data are routinely collected to remove non-neuronal fluctuations in the rs-fMRI signal during analysis. However, the feasibility and utility of collecting cardiorespiratory data in critically ill patients on a clinical MRI scanner are unknown. We concurrently acquired rs-fMRI (TR=1250ms), cardiac and respiratory data in 23 critically ill patients with acute severe traumatic brain injury (TBI), and 12 healthy control subjects. We compared the functional connectivity results after denoising with cardiorespiratory data (i.e., RETROICOR) with the results obtained after standard bandpass filtering. Rs-fMRI data in 7 patients could not be analyzed due to imaging artifacts. In 6 of the remaining 16 patients (37.5%), cardiorespiratory data were either incomplete or corrupted. In both patients and control subjects, the functional connectivity corrected with RETROICOR did not significantly differ from that corrected with bandpass filtering of 0.008-0.125 Hz. Collectively, these findings suggest that there is a limited feasibility and utility to prospectively acquire high-quality cardiorespiratory data during rs-fMRI in critically ill patients with severe TBI for physiological correction.
Identifying Causal Subsequent Memory Effects
Authors: Halpern David J. , Tubridy Shannon , Davachi Lila , Gureckis Todd M. 
Published: November 2021

AbstractOver 40 years of accumulated research has detailed associations between neuroimaging signals measured during a memory encoding task and later memory performance, across a variety of brain regions, measurement tools, statistical approaches and behavioral tasks. But the interpretation of these Subsequent Memory Effects (SMEs) remains unclear: if the identified signals reflect cognitive and neural mechanisms of memory encoding then the underlying neural activity must be causally related to future memory. However, almost all previous SME analyses do not control for potential confounders of this causal interpretation, such as serial position and item effects. We collect a large fMRI dataset and use a novel experimental design and analysis approach that allows us to statistically adjust for all exogenous confounding variables. We find that, using standard approaches without adjustment, we replicate several univariate and multivariate subsequent memory effects and are able to predict memory performance across people. However, we are unable to identify any signal that reliably predicts subsequent memory after adjusting for confounding variables, bringing into doubt the causal status of these effects. We apply the same approach to subjects’ judgments of learning collected during an encoding period, and show that these behavioral measures of encoding quality do predict memory after adjustments, suggesting that it is possible to measure signals at the time of encoding that reflect causal mechanisms but that existing neuroimaging measures may not have the precision and specificity to do so.
Bedtime to the brain: How infants sleep habits intertwine with sleep neurophysiology
Authors: Schoch Sarah F. , Jaramillo Valeria , Markovic Andjela , Huber Reto , Kohler Malcolm , Jenni Oskar G. , Lustenberger Caroline , Kurth Salome 
Published: November 2021

AbstractAdequate sleep is critical for development and facilitates the maturation of the neurophysiological circuitries at the basis of cognitive and behavioral function. Observational research has associated sleep problems in early life with worse later cognitive, psychosocial, and somatic health outcomes. Yet, the extent to which day-to-day sleep habits in early life relate to neurophysiology - acutely and long-term - remains to be explored. Here, we report that sleep habits in 32 healthy 6-month-olds assessed with actimetry are linked to fundamental aspects of their neurophysiology measured with high-density electroencephalography (hdEEG). Our study reveals four key findings: First, daytime sleep habits are linked to EEG slow wave activity (SWA). Second, habits of nighttime movement and awakenings from sleep are connected with spindle density. Third, habitual sleep timing is linked to neurophysiological connectivity quantified as Delta-coherence. And lastly, Delta-coherence at age 6 months predicts nighttime sleep duration at age 12 months. These novel findings widen our understanding that infants’ sleep habits are closely intertwined with three particular levels of neurophysiology: sleep pressure (determined by SWA), the maturation of the thalamocortical system (spindles), and the maturation of cortical connectivity (coherence). Our companion paper complements this insight in the perspective of later developmental outcomes: early thalamocortical connectivity (spindle density) at age 6 months predicts later behavioural status at 12 and 24 months. The crucial next step is to extend this concept to clinical groups to objectively characterize infants’ sleep habits “at risk” that foster later neurodevelopmental problems.HighlightsInfant’s habitual sleep behavior (actimetry) is linked with their sleep neurophysiology (EEG)Habits of daytime sleeping (naps) are related to slow wave activityInfant’s movements and awakenings at nighttime are linked to their sleep spindlesSleep timing (infant’s bedtimes) is associated with cortical connectivity in the EEG
Circulating Microvesicle-Associated Inducible Nitric Oxide Synthase Is a Novel Therapeutic Target to Treat Sepsis: Current Status and Future Considerations
Authors: Webber Robert J , Sweet Richard M , Webber Douglas S 
Published: November 2021

AbstractObjectiveTo determine if mitigating the harmful effects of circulating microvesicle-associated inducible nitric oxide (MV-A iNOS) in vivo increases the survival of challenged mice in three different mouse models of sepsis.DesignThe ability of anti-MV-A iNOS monoclonal antibodies (mAbs) to rescue challenged mice was assessed using three different mouse models of sepsis.SettingThe vivarium of a research laboratorySubjectsBalb/c miceInterventions: Mice were challenged with an LD80 dose of either lipopolysaccharide (LPS / endotoxin), TNFα, or MV-A iNOS and then treated at various times after the challenge with saline as control or with an anti-MV-A iNOS mAb as a potential immunotherapeutic to treat sepsis.Measurement and Main ResultsEach group of mice was checked daily for survivors, and Kaplan-Meier survival curves were constructed. Five different murine anti-MV-A iNOS mAbs from our panel of 24 murine anti-MV-A iNOS mAbs (1) were found to rescue some of the challenged mice. All five murine mAbs were used to genetically engineer humanized anti-MV-A iNOS mAbs by inserting the murine complementarity-determining regions (CDRs) into a human IgG1,kappa scaffold and expressing the humanized mAbs in CHO cells. Three humanized anti-MV-A iNOS mAbs were effective at rescuing mice from sepsis in three different animal models of sepsis. The effectiveness of the treatment was both time and dose dependent. Humanized anti-MV-A iNOS rHJ mAb could rescue up to 80% of the challenged animal if administered early and at a high dose.ConclusionsOur conclusions are MV-A iNOS is a novel therapeutic target to treat sepsis; anti-MV-A iNOS mAbs can mitigate the harmful effects of MV-A iNOS; the neutralizing mAb’s efficacy is both time and dose dependent; and a specifically targeted immunotherapeutic for MV-A iNOS could potentially save tens-of-thousands of lives annually and could result in improved antibiotic stewardship.
Executive control by fronto-parietal activity explains counterintuitive decision behavior in complex value-based decision-making
Authors: Matsui Teppei , Hattori Yoshiki , Tsumura Kaho , Aoki Ryuta , Takeda Masaki , Nakahara Kiyoshi , Jimura Koji 
Published: November 2021

AbstractIn real life, humans make decisions by taking into account multiple independent factors, such as delay and probability. Cognitive psychology suggests that cognitive control mechanisms play a key role when facing such complex task conditions. However, in value-based decision-making, it still remains unclear to what extent cognitive control mechanisms become essential when the task condition is complex. In this study, we investigated decision-making behaviors and underlying neural mechanisms using a multifactor gambling task where participants simultaneously considered probability and delay. Decision-making behavior in the multifactor task was modulated by both probability and delay. The behavioral effect of probability was stronger than delay, consistent with previous studies. Furthermore, in a subset of conditions that recruited fronto-parietal activations, reaction times were paradoxically elongated despite lower probabilistic uncertainty. Notably, such a reaction time elongation did not occur in control tasks involving single factors. Meta-analysis of brain activations suggested an association between the paradoxical increase of reaction time and strategy switching. Together, these results suggest a novel aspect of complex value-based decision-makings that is strongly influenced by fronto-parietal cognitive control.Highlights•A value-based decision task with concurrent delay and probabilistic uncertainty•Stronger behavioral effect of probability than delay•Paradoxically long reaction time despite low probabilistic uncertainty•The task activated fronto-parietal cognitive control network•Reaction time elongation coincided with activation similar to strategy switching
What drives employee's involvement in corporate volunteering? Bright and dark side of consequences to organization
Authors: Sekar Srinivasan 
Published: November 2021

PurposeThis study assesses the relevance of both individual and contextual factors as an antecedent to employee participation in corporate volunteering (CV) activities and affective organizational commitment and inter-role conflict as an outcome of employee volunteering. This study draws from the functional theory of motivation, social exchange theory and role strain perspective to explain hypothesized relationship of the study constructs.Design/methodology/approachA questionnaire survey was administered with 461 employee volunteers who had participated in company-sponsored volunteering programs. The authors adopted structural equation modeling (SEM) to test the study hypotheses.FindingsThe findings from the survey suggest that altruistic motives and organization CV capability will impact employee's participation in CV. The results highlight that employee participation in CV enhances affective organizational commitment, indicating that employee volunteering creates inter-role conflict.Research limitations/implicationsThough the study has identified inter-role conflict as a potentially unfavorable outcome, exploring when and how employee volunteering will create a negative effect will add significant value to organizations to protect the interest of their employees.Practical implicationsThis study provides insights to understand the relative effects of self- and other-oriented motives. The results suggest that organizations have more directed and carefully designed employee volunteering activities to enable more favorable benefits to employees.Originality/valueThis study contributes to expanding the knowledge on the phenomenon of employee volunteering by introducing and empirically validating an integrated framework of antecedents and consequences of employee volunteering.