bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the relationship between climatic factors and malaria transmission dynamics in Southwest states of Nigeria
Authors: Yusuf Owolabi , Okoronkwo Chukwu , Ademu Cyril , Silal Sheetal P. 
Published: May 2024

AbstractBackgroundIn order to combat malaria, numerous strategic initiatives have been deployed over the years, with the goal of eliminating the disease in Nigeria. Despite these efforts, malaria morbidity still persists across the nation, and is presently under control measures. Various factors, encompassing both climatic and non-climatic elements, significantly impact the dynamics of malaria transmission across the country. This study applied time series analysis methods to understand the relationship between climatic factors, particularly temperature and rainfall, and the occurrence of malaria in the Southwest area of Nigeria.MethodsThis study analysed monthly data on documented cases of uncomplicated malaria obtained from the District Health Information System version 2, overseen by the Federal Ministry of Health. Additionally, monthly rainfall and temperature data spanning from 2013 to 2021, acquired from the Nigeria Meteorological Agency, were analysed. The datasets used for analysis were accessed on June 7, 2022, for research purposes. We applied univariate time series models to analyse monthly data on average temperature, rainfall, and malaria cases. Subsequently, cross-correlation analyses were conducted to investigate the relationships between malaria case data and the corresponding rainfall and temperature patterns, following a pre-whitening process.ResultsThe patterns of malaria transmission exhibit variability among the various states within the Southwest region of Nigeria from 2013 to 2021. On average, Oyo State consistently recorded relatively higher temperatures compared to its neighbouring states. Conversely, Ondo State receives a higher average monthly rainfall. This state, similar to others in the region, experiences two distinct wet seasons, each characterised by different peak periods.In terms of temporal relationships, it is predicted that rainfall precedes malaria cases by one month across all the states. However, with regard to temperature, the five other states (excluding Osun state) lead by two months.ConclusionThe results of this study underscore the varied characteristics of malaria transmission patterns and climate change, even across the individual states within the Southwest region of the country. This recognition of variations in malaria transmission and climatic factors is valuable for policymakers as it enables them to strategically allocate and optimise the implementation of interventions at state-specific level, rather than at zonal level. These interventions might involve distributing and advocating for the use of insecticide-treated bed nets, indoor residual spraying, and seasonal malaria chemoprevention tailored to the unique requirements and circumstances at the state level.
Endoscopic ultrasound-guided biliary rendezvous after failed cannulation, and comparison between benign vs malignant biliopancreatic disorders: outcomes at a single tertiary-care center
Authors: Gornals Joan B , Sumalla-Garcia Albert , Quintana Sergi , Luna-Rodriguez Daniel , Velasquez-Rodriguez Julio G , Puigcerver-Mas Maria , Escuer Julia , Maisterra Sandra , Marin Mar , Munoa Virginia , Laquente Berta , Busquets Juli 
Published: May 2024

ABSTRACTBackgroundEndoscopic ultrasound (EUS)-guided biliary rendezvous (RV) is an EUS-assisted technique described as a rescue method in cases of failed biliary cannulation via endoscopic retrograde cholangiography (ERC). Current literature remains unclear regarding its current role. The study aim was to evaluate the effectiveness for biliary EUS-RV, and comparison between benign vs malignant biliopancreatic disorders.MethodsRetrospective observational study with prospective consecutive inclusion in a specific database from a tertiary-center. All patients with biliopancreatic diseases that underwent a EUS-assisted ERC between October-2010 and November-2022 for failed ERC were included. Main outcomes were technical/overall success. Secondary outcomes were safety, potential factors related to failure/success or safety; and a comparative analysis between EUS-RV and EUS-guided transmural drainage (TMD) in malignant cases.ResultsA total of 69 patients who underwent EUS-RV procedures, with benign and malignant pathologies (n=40 vs n=29), were included. Technical/overall success and related-adverse events (AEs) were 79.7% (95%CI, 68.3-88.4)/74% (95%CI, 61-83.7) and 24% (95%CI, 15.1-36.5), respectively. Failed cases were mainly related with guidewire manipulation. Seven failed RV were successfully rescued by EUS-TMD. On multivariable analysis, EUS-RV and malignant pathology was associated with a greater failure rate (technical success: OR,0.21; 95%CI,0.05-0.72; p=0.017), and higher AEs rate (OR,3.46; 95%CI,1.13-11.5; p=0.034). Also, the EUS-TMD group had greater technical success (OR,16.96; 95%CI,4.69-81.62; p<0.001) and overall success (OR, 3.09; 95%CI,1.18-8-16; p<0.026) with a lower AEs rate (OR,0.30; 95%CI,0.11-0.78; p=0.014) than EUS-RV in malignant disorders.ConclusionsEUS-RV is a demanding technique with better outcomes in benign than in malignant biliopancreatic diseases. Comparison of the EUS-TMD group on malignant disorders showed worse outcomes with EUS-RV. Given these findings, maybe EUS-RV is not the best option for malignant biliopancreatic disorders.
Intra-Ventricular Diastolic Hemodynamics under Pharmacological Stress in Patients with Ischemic Heart Disease: Analysis of 4D-Flow and Myocardial Flow Reserve using hybrid13N-ammonia Positron Emission Tomography/Magnetic Resonance
Authors: Endo Keiichiro , Fukushima Kenji , Katahira Masataka , Kiko Takatoyo , Yamakuni Ryo , Ukon Naoyuki , Shimizu Takeshi , Ishii Shiro , Yamaki Takayoshi , Nakazato Kazuhiko , Ito Hiroshi , Takeishi Yasuchika 
Published: May 2024

ABSTRACTObjectivesThis study aimed to explore the linkage between intra-left ventricular (LV) diastolic hemodynamics and coronary endothelial function, utilizing four-dimensional (4D) flow magnetic resonance imaging (MR) and myocardial flow reserve (MFR) through simultaneous acquisition using hybrid PETMR system in patients with ischemic heart disease (IHD).MethodsSixty-eight patients (mean 66 ± 15 years, male 55) with IHD who underwent rest-pharmacological stress13N-ammonia PET/MR were included. MFR and summed defect score (SSS and SRS for stress and rest) were obtained thorough rest-stress PET images. MR acquisition was performed simultaneously during PET scan to obtain rest-stress 4D flow datasets and followed by cine-MRI for the LV volume measurement. LV diastolic inflow(mL/s), peak velocity(cm/s), and averaged diastolic kinetic energy (KE)(μJ/mL) indexed with endo-diastolic volume were computed.ResultsDiastolic LV inflow parameters and KE significantly increased in stress scan compared to the rest (74.8 ± 17.5 cm/s vs. 64.5 ± 14.4 cm/s, p<0.0001; 10.1 ± 5.2 vs. 13.3 ± 7.8, p=0.0004 for peak velocity and KE, respectively). Stress KE showed a significant and weak correlation to MFR and SSS (r = 0.3, p=0.004; r=-0.4, p=0.002 for MFR and SSS, respectively). In patients with MFR above median value (1.76), stress KE significantly elevated from rest KE, while no significant change was observed for the patients with MFR below median (11.0 ± 4.6 vs. 16.2 ± 8.8, p=0.0002; 9.7 ± 5.4 vs. 10.3 ± 5.1 for rest vs. stress, respectively).ConclusionNon-invasive assessment of intra-LV diastolic hemodynamics derived from 4D flow MRI demonstrated significant alterations under stress, and was found to have a notable association with the extent of ischemia and coronary endothelial dysfunction.
Genetically edited human placental organoids cast new light on the role of ACE2 in placental development
Authors: Arthurs Anya L. , Dietrich Bianca , Knöfler Martin , Lushington Caleb J. , Thomas Paul Q. , Adikusuma Fatwa , Jankovic-Karasoulos Tanja , Smith Melanie D. , Pringle Kirsty G. , Roberts Claire T. 
Published: May 2024

AbstractACE2 expression is altered in pregnancy disorders andACE2gene variants are associated with several major pregnancy complications including small-for-gestational-age, fetal growth restriction and preeclampsia. This study utilised gene-editing to generate bothACE2knockout andACE2rs2074192 placental organoids, facilitating mechanistic studies into the role ofACE2in placental development, and the effect of fetal carriage ofACE2rs2074192 CC, CT and TT genotypes. Parameters of cell and organoid growth were measured, together with qPCR, Western Blotting, and ELISA assessments, in all groups from both organoid models. Here, we report thatACE2knockout results in delayed placental cell growth and increased cell death.ACE2knockout organoids had lower ACE protein expression, reduced organoid diameters and asymmetrical growth. Placental organoids with the ACE2 rs2074192 TT genotype had significantly higher expression ofACE2mRNA and ACE2 protein with elevated ACE2:ACE expression ratio and no change in ACE protein expression. Despite increased expression of ACE2 protein, ACE2 enzyme activity was significantly decreased in ACE2 rs2074192 TT placental organoids. TT organoids also had reduced diameters and asymmetrical growth. Our research provides new molecular understanding of the role of ACE2 in placental development, with potential implications for pregnancy in carriage of theACE2rs2074192 gene variant.
Fight, Retreat, Repeat: Field observation of male-male agonistic behavior in the wood-feeding cockroach,Panesthia angustipennis spadica(Dictyoptera: Blattodea: Blaberidae)
Authors: Osaki Haruka , Nakazono Tomohiro , Yabe Kiyotaka , Takata Mamoru , Mikaelyan Aram 
Published: May 2024

AbstractConflict is one of the most critical factors affecting the behavior of animals related to their reproduction and survival, with aggressive interactions being central to acquiring resources or mating partners. This phenomenon is more common among males than females, impacting reproduction strategy and beginning of biparental care. Investigating such interactions in species closely related to social species can be illuminating, offering valuable insights into the factors that influence the emergence and maintenance of more complex social behaviors. In this context, we present a field study of male-male agonistic behavior in the wood-feeding cockroach,Panesthia angustipennis. Panesthiais the closest genus to the subsocial genusSalganea, which is known for its biparental care. Our field observations reveal a characteristic behavior where one male pushes a rival away from a female. The victorious male repeatedly returns to a specific site near the female, suggesting a strategy to minimize unnecessary conflict or protect the female. This behavior provides insights into the potential evolutionary strategies that may have evolved in the common ancestor shared bySalganeaandPanesthia. Notably, the displaced males persistently reengage, highlighting the high resource value attributed to females and the consequential intensity of male competition. This study not only sheds light on the aggressive and pacifist tendencies inP. angustipennisbut also contributes to understanding the evolutionary development of social structures inSalganea. Further experimental investigations into the aggressive behaviors ofP. angustipenniswill enhance our comprehension of the factors shaping the evolution of sociality in these species.
Neurocomputational Mechanisms Underlying Maladaptive Self-Belief Formation in Depression
Authors: Czekalla Nora , Schröder Alexander , Mayer Annalina V , Stierand Janine , Stolz David S , Kube Tobias , Korn Christoph W. , Wilhelm-Groch Ines , Klein Jan Philipp , Paulus Frieder M , Krach Sören , Müller-Pinzler Laura 
Published: May 2024

AbstractMaladaptive self-beliefs are a core symptom of major depressive disorder. These are perpetuated by negatively biased feedback processing. Understanding the neurocomputational mechanisms of biased belief updating may help to counteract maladaptive beliefs. The present study uses functional neuroimaging to examine neural activity associated with prediction error-based learning in persons with major depression and healthy controls. We hypothesized that increased symptom burden is associated with negatively biased self-belief formation and altered neural tracking of social feedback. Results showed that a higher symptom burden was associated with forming more negative self-beliefs and more positive beliefs about others. This bias was driven by reduced learning from positive prediction errors in depression. Neural reactivity of the insula showed increased tracking of more negative self-related prediction errors. The interplay of increased neural responsiveness to negative feedback and reduced learning from positive feedback may contribute to the persistence of maladaptive self-beliefs and, thus, the maintenance of depression.
The molecular mechanism of on-demand sterol biosynthesis at organelle contact sites
Authors: Zung Naama , Aravindan Nitya , Boshnakovska Angela , Valenti Rosario , Preminger Noga , Jonas Felix , Yaakov Gilad , Willoughby Mathilda M. , Homberg Bettina , Keller Jenny , Kupervaser Meital , Dezorella Nili , Dadosh Tali , Wolf Sharon G. , Itkin Maxim , Malitsky Sergey , Brandis Alexander , Barkai Naama , Fernández-Busnadiego Rubén , Reddi Amit R. , Rehling Peter , Rapaport Doron , Schuldiner Maya 
Published: May 2024

AbstractContact-sites are specialized zones of proximity between two organelles, essential for organelle communication and coordination. The formation of contacts between the Endoplasmic Reticulum (ER), and other organelles, relies on a unique membrane environment enriched in sterols. However, how these sterol-rich domains are formed and maintained had not been understood. We found that the yeast membrane protein Yet3, the homolog of human BAP31, is localized to multiple ER contact sites. We show that Yet3 interacts with all the enzymes of the post-squalene ergosterol biosynthesis pathway and recruits them to create sterol-rich domains. Increasing sterol levels at ER contacts causes its depletion from the plasma membrane leading to a compensatory reaction and altered cell metabolism. Our data shows that Yet3 provides on-demand sterols at contacts thus shaping organellar structure and function. A molecular understanding of this protein’s functions gives new insights into the role of BAP31 in development and pathology.
Collagen fibril formation at the plasma membrane occurs independently from collagen secretion
Authors: Pickard Adam , Garva Richa , Adamson Antony , Calverley Ben C. , Hoyle Anna , Hayward Christina E. , Spiller David , Lu Yinhui , Hodson Nigel , Mandolfo Oriana , Kim Kevin K. , Bou-Gharios George , Swift Joe , Bigger Brian , Kadler Karl E. 
Published: May 2024

SummaryCollagen fibrils are the primary supporting scaffold of vertebrate tissues but how they are assembled is unclear. Here, using CRISPR-tagging of type I collagen and SILAC labelling, we elucidate the cellular mechanism for the spatiotemporal assembly of collagen fibrils, in cultured fibroblasts. Our findings reveal multifaceted trafficking of collagen, including constitutive secretion, intracellular pooling, and plasma membrane-directed fibrillogenesis. Notably, we differentiate the processes of collagen secretion and fibril assembly and identify the crucial involvement of endocytosis in regulating fibril formation. By employing Col1a1 knockout fibroblasts we demonstrate the incorporation of exogenous collagen into nucleation sites at the plasma membrane through these recycling mechanisms. Our study sheds light on the assembly process and its regulation in health and disease. Mass spectrometry data are available via ProteomeXchange with identifier PXD036794.
The LC3-interacting region of NBR1 is a protein interaction hub enabling optimal flux
Authors: North Brian J , Ohnstad Amelia E , Ragusa Michael J , Shoemaker Christopher J 
Published: May 2024

ABSTRACTDuring autophagy, potentially toxic cargo is enveloped by a newly formed autophagosome and trafficked to the lysosome for degradation. Ubiquitinated protein aggregates, a key target for autophagy, are identified by multiple autophagy receptors. NBR1 is an archetypal autophagy receptor and an excellent model for deciphering the role of the multivalent, heterotypic interactions made by cargo-bound receptors. Using NBR1 as a model, we find that three critical binding partners – ATG8-family proteins, FIP200, and TAX1BP1 – each bind to a short linear interaction motif (SLiM) within NBR1. Mutational peptide arrays indicate that these binding events are mediated by distinct overlapping determinants, rather than a single, convergent, SLiM. AlphaFold modeling underlines the need for conformational flexibility within the NBR1 SLiM, as distinct conformations mediate each binding event. To test the extent to which overlapping SLiMs exist beyond NBR1, we performed peptide binding arrays on >100 established LC3-interacting regions (LIRs), revealing that FIP200 and/or TAX1BP1 binding to LIRs is a common phenomenon and suggesting LIRs as protein interaction hotspots. Comparative analysis of phosphomimetic peptides highlights that while FIP200 and Atg8-family binding are generally augmented by phosphorylation, TAX1BP1 binding is nonresponsive, suggesting differential regulation of these binding events. In vivo studies confirm that LIR-mediated interactions with TAX1BP1 enhance NBR1 activity, increasing autophagosomal delivery by leveraging an additional LIR from TAX1BP1. In sum, these results reveal a one-to-many binding modality in NBR1, providing key insights into the cooperative mechanisms among autophagy receptors. Furthermore, these findings underscore the pervasive role of multifunctional SLiMs in autophagy, offering substantial avenues for further exploration into their regulatory functions.
A conserved chronobiological complex timesC. elegansdevelopment
Authors: Spangler Rebecca K. , Braun Kathrin , Ashley Guinevere E. , van der Does Marit , Wruck Daniel , Ramos Coronado Andrea , Ragle James Matthew , Iesmantavicius Vytautas , Morales Moya Lucas J. , Jonnalagadda Keya , Partch Carrie L. , Großhans Helge , Ward Jordan D. 
Published: May 2024

AbstractThe mammalian PAS-domain protein PERIOD (PER) and itsC. elegansorthologue LIN-42 have been proposed to constitute an evolutionary link between two distinct, circadian and developmental, timing systems. However, while the function of PER in animal circadian rhythms is well understood molecularly and mechanistically, this is not true for LIN-42’s function in timing rhythmic development. Here, using targeted deletions, we find that the LIN-42 PAS domains are dispensable for the protein’s function in timing molts. Instead, we observe arrhythmic molts upon deletion of a distinct sequence element, conserved with PER. We show that this element, designated CK1δ-binding domain (CK1BD), mediates stable binding to KIN-20, theC. elegansCK1δ/ε orthologue. We demonstrate that CK1δ phosphorylates LIN-42 and define two conserved helical motifs in the CK1BD, CK1BD-A and CK1BD-B, that have distinct roles in controlling CK1δ-binding and kinase activityin vitro. KIN-20 and the LIN-42 CK1BD are required for proper molting timingin vivo, and loss of LIN-42 binding changes KIN-20 subcellular localization. The interactions mirror the central role of a stable circadian PER–CK1 complex in setting a robust ∼24-hour period. Hence, our results establish LIN-42/PER – KIN-20/CK1δ/ε as a functionally conserved signaling module of two distinct chronobiological systems.
Deep learning based reconstruction of embryonic cell-division cycle from label-free microscopy time-series of evolutionarily diverse nematodes
Authors: Khatri Dhruv , Athale Chaitanya A. 
Published: May 2024

AbstractMicroscopy of cellular dynamics during embryogenesis of non-model organisms can be tech- nically challenging due to limitations of molecular labelling methods. Label-free differential interference contrast (DIC) microscopy of the first embryonic cell division of nematodes related toCaenorhabditis eleganshas been successfully employed to examine the constraints and divergence of intra-cellular mechanisms during this asymmetric cell division. However, identifying stages of the cell division cycle were performed interactively, pointing to a need to automate of cell stage identification from DIC microscopy. To this end, we have trained deep convolutional neural networks (CNNs), both pre-existing such as ResNet, VGGNet and EfficientNet, and a customized shallow network, EvoCellNet, to automatically classify first-embryonic division into the stages: (i) pro-nuclear migration and (ii) centration and rotation, (iii) spindle elongation and (iv) cytokinesis, with all networks performing with 91% or greater accuracy. The activations of the networks superimposed on the images result in segmentation-free detection of intracellular features such as pro-nuclei, spindle and spindle- poles in case of the shallow EvoCellNet, while ResNet, VGGNet and and EfficientNet detect large-scale, features that are less biologically meaningful. The UMAP space representation combined with support vector machines (SVM) allows for stage boundary identification and recovers a cyclical map connecting the states (i) to (iv) of the division. This approach could be used to automate quantification of cell division stages and sub-cellular dynamics without explicit labelling in label-free microscopy.SummaryWe have trained multiple convolutional neural networks (CNNs) to classify the stages of cell division from the first embryonic division of diverse nematodes, evolutionarily related toCaenorhabditis elegans. We find two classifiers, VggNet and a customized EvoCellNet, can detect intracellular features and a UMAP representation can reconstruct the cyclical progression of first embryonic division from related species.
The structural landscape of Microprocessor mediated pri-let-7miRNA processing
Authors: Garg Ankur , Shang Renfu , Cvetanovic Todor , Lai Eric C. , Joshua-Tor Leemor 
Published: May 2024

SummarymiRNA biogenesis is initiated upon cleavage of a primary miRNA (pri-miRNA) hairpin by the Microprocessor (MP), composed of the Drosha RNase III enzyme and its partner DGCR8. Multiple pri-miRNA sequence motifs affect MP recognition, fidelity, and efficiency. Here, we performed cryo-EM and biochemical studies of several let-7 family pri-miRNAs in complex with human MP. We show that MP has the structural plasticity to accommodate a range of pri-miRNAs. These structures revealed key features of the 5’ UG sequence motif, more comprehensively represented as the “fUN” motif. Our analysis explains how cleavage of class-II pri-let-7 members harboring a bulged nucleotide generates a noncanonical precursor with a 1-nt 3’ overhang. Finally, the MP-SRSF3-pri-let-7f1 structure reveals how SRSF3 contributes to MP fidelity by interacting with the CNNC-motif and Drosha’s PAZ-like domain. Overall, this study sheds light on the mechanisms for flexible recognition, accurate cleavage, and regulated processing of different pri-miRNAs by MP.