bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Decision Support Systems implementation in Africa: a systemic review
Authors: Nortey Jacob Nii Noye , Takyi Kate , Adabo Andrew , Suleiman Rashida 
Published: October 2023

AbstractThe healthcare system in Africa is characterized by the lack of trained clinicians, resources, brain drain and quality care processes. To mitigate these challenges, some African countries have resorted to the use of health information technologies such as the Clinical Decision Support System (CDSS). Globally, CDSS implementations in the health sector have been reported to have reduced medical error, increased hospital accessibility and standard of care. Studies on the number of implemented CDSS in Africa were found to be limited since only a few are available. Despite this setback, the few implemented CDSSs are effective, efficient, and reliable in the diagnosis of diseases. In order to fully ascertain the impact of CDSS implementation in African counties, we evaluated the documented CDSS programs that are in operation. An extensive search was performed on Google Scholar, PubMed, and SCOPUS. About 38 (thirty-eight) publications were identified, of which some met the inclusion criteria. Limited implementation of CDSS was observed in the African countries. The review showed promising impacts of CDSS in African healthcare centers especially in the diagnose and treatment of pediatric and maternal related disease.
An axonemal intron splicing program sustainsPlasmodiummale development
Authors: Guan Jiepeng , Wu Peijia , Mo Xiaoli , Zhang Xiaolong , Liang Wenqi , Zhang Xiaoming , Jiang Lubing , Li Jian , Cui Huiting , Yuan Jing 
Published: October 2023

AbstractDifferentiation of male gametocyte into flagellated fertile male gamete relies on the axoneme assembly, a major component of male development for mosquito transmission of malaria parasite. RNA-binding protein (RBP)-mediated post-transcription regulation plays important roles in eukaryotic sexual development, including thePlasmodiumfemale development. However, the role of RBP in defining thePlasmodiummale transcriptome and its function in the male gametogenesis remain elusive. Here, we screened the gender expression of the genome-wide RBPs and identified an undescribed male-specific RBP geneRbpm1in thePlasmodium. RBPm1 is localized in the nucleus of male gametocytes. RBPm1-deficient parasites fail to assemble the axoneme for male gametogenesis and thus mosquito transmission. RBPm1 interacts with spliceosome E complex and regulates splicing initiation of certain introns in a group of 26 axonemal genes. RBPm1 deficiency results in intron retention and protein loss of these axonemal genes. Intron deletion restores axonemal proteins expression and partially rectifies axonemal defects in RBPm1-null gametocytes. Further splicing assays in both reporter and endogenous genes exhibit stringent recognition of the axonemal introns by RBPm1. Therefore, the splicing activator RBPm1 and its target introns constitute an axonemal intron splicing program in the post-transcription regulation essential forPlasmodiummale development.
Biomolecular condensates form spatially inhomogeneous network fluids
Authors: Dar Furqan , Cohen Samuel R. , Mitrea Diana M. , Phillips Aaron H. , Nagy Gergely , Leite Wellington C. , Stanley Christopher B. , Choi Jeong-Mo , Kriwacki Richard W. , Pappu Rohit V. 
Published: October 2023

AbstractThe functions of biomolecular condensates are thought to be influenced by their material properties, and these will be determined by the internal organization of molecules within condensates. However, structural characterizations of condensates are challenging, and rarely reported. Here, we deploy a combination of small angle neutron scattering, fluorescence recovery after photobleaching, and coarse-grained molecular dynamics simulations to provide structural descriptions of model condensates that are formed by macromolecules from nucleolar granular components (GCs). We show that these minimal facsimiles of GCs form condensates that are network fluids featuring spatial inhomogeneities across different length scales that reflect the contributions of distinct protein and peptide domains. The network-like inhomogeneous organization is characterized by a coexistence of liquid- and gas-like macromolecular densities that engenders bimodality of internal molecular dynamics. These insights suggest that condensates formed by multivalent proteins share features with network fluids formed by systems such as patchy or hairy colloids.
The cytoplasmic phosphate level has a central regulatory role in the phosphate starvation response ofCaulobacter crescentus
Authors: Billini Maria , Hoffmann Tamara , Kühn Juliane , Bremer Erhard , Thanbichler Martin 
Published: October 2023

ABSTRACTIn bacteria, the availability of environmental inorganic phosphate is typically sensed by the conserved PhoR-PhoB two-component signal transduction pathway, which is thought to use the flux through the PstSCAB phosphate transporter as a readout of the extracellular phosphate level to control phosphate-responsive genes. While the sensing of environmental phosphate is well-investigated, the regulatory effects of cytoplasmic phosphate are unclear. Here, we disentangle the physiological and transcriptional responses ofCaulobacter crescentusto changes in the environmental and cytoplasmic phosphate levels by uncoupling phosphate uptake from the activity of the PstSCAB system, using an additional, heterologously produced phosphate transporter. This approach reveals a two-pronged response ofC. crescentusto phosphate limitation, in which PhoR-PhoB signaling mostly facilitates the utilization of alternative phosphate sources, whereas the cytoplasmic phosphate level controls the morphological and physiological adaptation of cells to growth under global phosphate limitation. These findings open the door to a comprehensive understanding of phosphate signaling in bacteria.
The serine/threonine kinase CcAkt regulates the fertility ofCoridius chinensis
Authors: Feng Jinyu , Du Juan , Li Shangwei , Chen Xingxing 
Published: October 2023

AbstractAkt (also known as protein kinase B) belongs to the multifunctional serine/threonine kinase family and is an important component of the insulin signaling pathway that plays a key role in many biological processes such as cell growth, proliferation, and survival. However, few studies have reported the effect of Akt on reproduction in Hemiptera. In this study, we cloned and characterized theAktgene fromCoridius chinensis(CcAkt). The open reading frame ofCcAkthas a length of 1,563 bp and encodes 520 amino acids. It has a conserved pleckstrin homology domain, a serine/threonine protein kinase catalytic domain, and a serine/threonine protein kinase domain. Phylogenetic analysis showed thatCcAktandHhAktofHalyomorpha halyshad the highest similarity. Analysis of temporal and spatial expression patterns revealed thatCcAktis expressed throughout development and in various tissues ofC. chinensisadults.CcAktexpression was high in female adult and the fourth instar nymph stage ofC. chinensis. InC. chinensisadult,CcAktexpression was highest in the testis and ovary. Injection of bovine insulin inducedCcAktexpression, whereas that of 20-hydroxyecdysone significantly reducedCcAktexpression. Both hormones, however, induced the expression ofvitellogenin(Vg) andvitellogenin receptor(VgR). In unmated females,CcAktknockout resulted in decreased expression ofCcVgandCcVgR, stunted the development of the ovarioles, decreased the number of eggs and hatching rate. These findings suggest that CcAkt may be involved in regulating the reproduction ofC. chinensis.
Optimizing Cryo-EM Structural Analysis of Gi-coupling Receptors via Engineered Gtand Nb35 Application
Authors: Oshima Hidetaka S. , Sano Fumiya K. , Akasaka Hiroaki , Iwama Aika , Shihoya Wataru , Nureki Osamu 
Published: October 2023

AbstractCryo-EM single particle analysis has recently facilitated the high-resolution structural determination of numerous GPCR-G complexes. Diverse methodologies have been devised with this trend, and in the case of GPCR-Gicomplexes, scFv16, an antibody that recognizes the intricate interface of the complex, has been mainly implemented to stabilize the complex. However, owing to their flexibility and heterogeneity, structural determinations of GPCR-Gicomplexes remain both challenging and resource-intensive. By employing eGαt, which exhibits binding affinity to modified nanobody Nb35, the cryo-EM structure of Rhodopsin-eGαtcomplex was previously reported. Using this modified G protein, we determined the structure of the ETB-eGtcomplex bound to the modified Nb35. The determined structure of ETBreceptor was the same as the previously reported ETB-Gicomplex, and the resulting dataset demonstrated significantly improved anisotropy. This modified G protein will be utilized for the structural determination of other GPCR-Gicomplexes.HighlightsThe study introduces the engineered G protein subunit eGαT, which enhances the resolution of GPCR-G protein structures by suppressing G protein conformational fluctuations and is particularly beneficial for Gi-coupled receptors.The cryo-EM structure of the ETBreceptor complexed with eGt-Nb35 reveals improved map quality, reduced anisotropy, and isotropic density distribution, increasing the accuracy of structural analysis.Structural comparison between ETB-Giand ETB-eGtreveals similar receptor-G protein interactions, demonstrating the utility of eGt-Nb35 for studying GPCR-Gicomplexes and the potential for broader applications within the Gifamily.
Integrator-mediated clustering of poised RNA polymerase II synchronizes histone transcription
Authors: Lu Feiyue , Park Brandon J. , Fujiwara Rina , Wilusz Jeremy E. , Gilmour David S. , Lehmann Ruth , Lionnet Timothée 
Published: October 2023

AbstractNumerous components of the transcription machinery, including RNA polymerase II (Pol II), accumulate in regions of high local concentration known as clusters, which are thought to facilitate transcription. Using the histone locus ofDrosophilanurse cells as a model, we find that Pol II forms long-lived, transcriptionally poised clusters distinct from liquid droplets, which contain unbound and paused Pol II. Depletion of the Integrator complex endonuclease module, but not its phosphatase module or Pol II pausing factors disperses these Pol II clusters. Consequently, histone transcription fails to reach peak levels during S-phase and aberrantly continues throughout the cell cycle. We propose that Pol II clustering is a regulatory step occurring near promoters that limits rapid gene activation to defined times.One Sentence SummaryUsing theDrosophilahistone locus as a model, we show that clustered RNA polymerase II is poised for synchronous activation.
Digital gait measures capture 1-year progression in early-stage spinocerebellar ataxia type 2
Authors: Seemann Jens , Daghsen Lina , Cazier Mathieu , Lamy Jean-Charles , Welter Marie-Laure , Giese Martin A. , Synofzik Matthis , Durr Alexandra , Ilg Winfried , Coarelli Giulia 
Published: October 2023

AbstractBACKGROUNDWith disease-modifying drugs in reach for cerebellar ataxias, fine-grained digital health measures are highly warranted to complement clinical and patient-reported outcome measures in upcoming treatment trials and treatment monitoring. These measures need to demonstrate sensitivity to capture change, in particular in the early stages of the disease.OBJECTIVETo unravel gait measures sensitive to longitudinal change in the - particularly trial-relevant- early stage of spinocerebellar ataxia type 2 (SCA2).METHODSMulti-center longitudinal study with combined cross-sectional and 1-year interval longitudinal analysis in early-stage SCA2 participants (n=23, including 9 pre-ataxic expansion carriers; medianATXN2CAG repeat expansion 38±2; median SARA [Scale for the Assessment and Rating of Ataxia] score 4.83±4.31). Gait was assessed using three wearable motion sensors during a 2-minute walk, with analyses focusing on gait measures of spatiotemporal variability shown sensitive to ataxia severity, e.g. lateral step deviation.RESULTSWe found significant changes for gait measures between baseline and 1-year follow-up with large effect sizes (lateral step deviation p=0.0001, effect size rprb=0.78), whereas the SARA score showed no change (p=0.67). Sample size estimation indicates a required cohort size of n=43 to detect a 50% reduction in natural progression. Test-retest reliability and Minimal Detectable Change analysis confirm the accuracy of detecting 50% of the identified 1-year change.CONCLUSIONSGait measures assessed by wearable sensors can capture natural progression in early-stage SCA2 within just one year – in contrast to a clinical ataxia outcome. Lateral step deviation thus represents a promising outcome measure for upcoming multi-centre interventional trials, particularly in the early stages of cerebellar ataxia.
Astrocytes Control Recent and Remote Memory Strength by Affecting the Recruitment of the CA1→ACC Projection to Engrams
Authors: Refaeli Ron , Kreisel Tirzah , Groysman Maya , Goshen Inbal 
Published: October 2023

AbstractRecent and remote memories are encoded throughout the brain in ‘Engrams’: cell ensembles formed during acquisition, and upon their reactivation, a specific memory can be recalled. The maturation of engrams from recent to remote time points involves the recruitment of CA1 neurons projecting to the anterior cingulate cortex (CA1→ACC). Various modifications to CA1 astrocytes, to the Gq- or Gi-GPCR pathways, during memory acquisition were shown to affect recent and remote recall in seemingly contradictory ways. To address the inconsistency, we applied transgenic approaches for ensemble identification, CLARITY, retro-AAV virus for circuit mapping, and chemogenetics in astrocytes for functional investigation. We manipulated the activity of either Gq- or Gi-pathways in CA1 astrocytes during memory acquisition and tagged cFos+ engram cells and CA1→ACC cells during recent and remote recall in the same animals. The behavioral results were coupled with changes in the recruitment of CA1→ACC projection cells to the engram, demonstrated by the number of CA1→ACC projecting cells in the engram as well as the number of axons projecting from the CA1 engram toward the ACC: Gq pathway activation in astrocytes caused enhancement of recent recall alone and was accompanied by earlier recruitment of CA1→ACC projecting cells to the engram. In contrast, when activating the Gi pathway in astrocytes during acquisition, only remote recall was impaired, and CA1→ACC projecting cells were not recruited during remote memory. Finally, we provide a simple working model, hypothesizing that astrocytes control behavioral performance by targeting the CA1→ACC projection. Specifically, that Gq- and Gi-pathway activation affect memory differently, but do so by modulating the same mechanism. These findings illuminate the importance of astrocytes in the acquisition of fear memory and their implications on recent and remote recall.
Proteome birthdating reveals age-selectivity of protein ubiquitination
Authors: Meadow Michael E. , Broas Sarah , Hoare Margaret , Alimohammadi Fatemeh , Welle Kevin A. , Swovick Kyle , Hryhorenko Jennifer R. , Martinez John C. , Biashad Seyed Ali , Seluanov Andrei , Gorbunova Vera , Buchwalter Abigail , Ghaemmaghami Sina 
Published: October 2023

AbstractWithin a cell, proteins have distinct and highly variable half-lives. As a result, the molecular ages of proteins can range from seconds to years. How the age of a protein influences its environmental interactions is a largely unexplored area of biology. To investigate the age-selectivity of cellular pathways, we developed a methodology termed “proteome birthdating” that barcodes proteins based on their time of synthesis. We demonstrate that this approach provides accurate measurements of protein turnover kinetics without the requirement for multiple kinetic time points. As a first use case of the birthdated proteome, we investigated the age distribution of the human ubiquitinome. Our results indicate that the vast majority of ubiquitinated proteins in a cell consist of newly synthesized proteins and that these young proteins constitute the bulk of the degradative flux through the proteasome. Rapidly ubiquitinated nascent proteins are enriched in cytosolic subunits of large protein complexes. Conversely, proteins destined for the secretory pathway and vesicular transport have older ubiquitinated populations. Our data also identified a smaller subset of very old ubiquitinated cellular proteins that do not appear to be targeted to the proteasome for rapid degradation. Together, our data provide an age census of the human ubiquitinome and establish proteome birthdating as a robust methodology for investigating the protein age-selectivity of diverse cellular pathways.Significance StatementCellular proteins have widely different ages - whereas some have been recently synthesized, others have existed in the cell for days or even years. How a protein’s age influences its functions and interactions is largely unknown because it is difficult to globally differentiate proteins based on their time of synthesis. To address this challenge, we developed an analytical method named “proteome birthdating” that can partition cellular proteins into multiple discernible age groups. As an example application, we used proteome birthdating to examine the protein age-selectivity of the ubiquitin proteasome system, a major protein degradation pathway in eukaryotes. Our results show that proteins destined for degradation by this pathway consist of either particularly young or particularly old proteins, with the former being the predominant population. Together, our results establish proteome birthdating as a useful approach for analyzing the turnover of proteins and investigating the functional consequences of their age.
Hierarchical replay of multi-regional sequential spiking associated with working memory
Authors: Huang Ermeng , Xu Da , Zhu Huangao , Chen Zhaoqin , Chen Yulei , Zhang Xiaoxing , Li Chengyu T. 
Published: October 2023

AbstractHow does millisecond-scale neural activity mediate behaviors over seconds? We recorded brain-wide activity in mice performing an olfactory working-memory task to decipher cross-region organization of activity. Spike-correlograms revealed millisecond within- and cross-region spike couplings, more prominent among neurons encoding similar memories. Spike coupling linked neurons into motifs of chains, single loops, and nested loops, especially among hippocampal and prefrontal-cortex neurons. Direction of spike coupling and activity chains was in line with that of memory-associated activity waves. Intriguingly, activity motifs were replayed before and after task performance, and during inter-trial intervals. Motifs were hierarchically organized, with progressively increasing time constants and the number of participating neurons. Thus, hierarchically organized and replayed cross-region spiking motifs are modulated on demand during delay period to mediate perceptual working memory.One Sentence SummaryNested activity motifs of chains, single loops, and nested loops, with progressively increasing time constants and number of participating neurons, are hierarchically organized and replayed to mediate perceptual working-memory maintenance.
Impact of sampling site on diagnostic test accuracy of RT-PCR in diagnosing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection since the emergence of omicron: a systematic review and meta-analysis
Authors: Saal-Bauernschubert Lena , Wagner Carina , Fomenko Alexey , Dähne Theo , Bora Ana-Mihaela , Janka Heidrun , Stangl Stephanie , Skoetz Nicole , Weibel Stephanie 
Published: October 2023

AbstractNasopharyngeal sampling (NP) is the routine standard for SASR-CoV-2 detection using reverse transcription polymerase chain reaction (RT-PCR). In this systematic review, we assessed diagnostic test accuracy of alternative sampling sites compared to NP for RT-PCR testing of Omicron (sub)-variants.We systematically searched for studies from January 2022 until February 2023 investigating any type of respiratory sample for RT-PCR in people with suspected, known, or known absence of SARS-CoV-2 Omicron infection. Data were pooled for each comparison using the bivariate model, sensitivity and specificity was estimated with 95% confidence intervals (CIs). Risk of bias was assessed with QUADAS-2 tool, certainty of evidence with GRADE.We included three cohort-type cross-sectional studies (1,003 participants). Saliva versus NP sampling in three studies showed a sensitivity of 92% (95% CI 87% to 96%) and a specificity of 94% (95% CI 83% to 98%). AN versus NP sampling in one study showed a sensitivity of 90% (95% CI 82% to 95%) and a specificity of 99% (95% CI 95% to 100%). Certainty of evidence for sensitivity and specificity of both comparisons was low to very low.Based on the current very low- to low-certainty evidence, we are uncertain about accuracy of different sampling sites for RT-PCR.
Characterising phagocytes and measuring phagocytosis from liveGalleria mellonellalarvae
Authors: Campbell Jennie S. , Bebes Attila , Pradhan Arnab , Yuecel Raif , Brown Al , Wakefield James G. 
Published: October 2023

AbstractOver the last 20 years, the larva of the greater waxmoth,Galleria mellonella, has rapidly increased in popularity as anin vivomammalian replacement model organism for the study of human pathogens. Despite this, experimental readouts of response to infection are generally limited to observing the melanisation cascade – where the organism turns black as part of the systemic immune response – and quantifying larval death over time. As an invertebrate,Galleriaharbour an innate immune system comprised of both humoral components and a repertoire of innate immune cells – termed hemocytes. Though information on subtypes of hemocytes exist, there are conflicting reports on their exact number and function. Flow cytometry has previously been used to assayGalleriahemocytes, but protocols include both centrifugation and fixation - physical methods which have the potential to affect hemocyte morphology prior to analysis. Here, we present a method for live hemocyte analysis by flow cytometry, revealing thatGalleriahemocytes constitute only a single resolvable population, based on relative size or internal complexity. Using fluorescent zymosan particles, we extend our method to show that up to 80% of theGalleriahemocyte population display phagocytic capability. Finally, we demonstrate that the developed assay reliably replicatesin vitrodata, showing that cell wall β-1,3-glucan masking byCandida albicanssubverts phagocytic responses. As such, our method provides a new tool with which to rapidly assess phagocytosis and understand live infection dynamics inGalleria.