bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavioral state regulates the dynamics of memory consolidation
Authors: Silva N. Tatiana , Ribeiro Maria Inês , Carey Megan R. 
Published: July 2024

ABSTRACTLong-term memories are consolidated over time, progressively becoming more stable and resistant to interference. Memory consolidation occurs offline and often involves transfer of memories from one brain site to another. For many motor memories, consolidation is thought to involve early learning in cerebellar cortex that is subsequently transferred to the cerebellar nuclei. Here we report that in mice, engaging in locomotor activity during training in a classical conditioning task shifts the critical time window for memory consolidation, from just after training sessions, to between trials, within sessions. This temporal shift requires natural patterns of cerebellar granule cell activity during intertrial intervals and is accompanied by earlier involvement of the downstream cerebellar nucleus. These results reveal that the critical time window for cerebellar memory consolidation can be surprisingly brief, on a timescale from seconds to minutes, and that it is dynamically regulated by behavioral state.
PINK1-G411S mutant increases kinase stability and enhances mitochondrial-linked functions
Authors: Gonçalves Filipa B. , Enguita Francisco J. , Morais Vanessa A. 
Published: July 2024

ABSTRACTPINK1, a mitochondria targeted Serine/Threonine kinase, regulates ATP production by phosphorylating the Complex I subunit NdufA10. However, when in the presence of depolarized mitochondria, PINK1 phosphorylates ubiquitin and Parkin triggering mitochondria clearance. Mutations in PINK1 have been linked to early-onset recessive familial forms of Parkinson’s disease (PD). Deficits in Complex I enzymatic activity and an increase in oxidative damage have been identified in multiple brain regions of PD patients. Unravelling how PINK1 activity regulates mitochondria fate is pivotal. In the present study we characterized how human PD-related PINK1 mutants affect major PINK1 functions. Using molecular dynamics, we gain mechanistic insight into how specific mutations alter the tertiary structure and stability of PINK1’s ATP-binding pocket, leading to an increased rigidity and stability. More importantly, we report a structural explanation for the enhanced kinase function of the PINK1-G411S mutant.
Denoising Longitudinal Social Media for Pandemic Monitoring
Authors: Lin Shixu , Garay Lucas , Hua Yining , Guo Zhijiang , Xu Xiaolin , Yang Jie 
Published: July 2024

AbstractObjectiveCurrent studies leveraging social media data for disease monitoring face challenges like noisy colloquial language and insufficient tracking of user disease progression in longitudinal data settings. This study aims to develop a pipeline for collecting, cleaning, and analyzing large-scale longitudinal social media data for disease monitoring, with a focus on COVID-19 pandemic.Materials and MethodsThis pipeline initiates by screening COVID-19 cases from tweets spanning February 1, 2020, to April 30, 2022. Longitudinal data is collected for each patient, two months before and three months after self-reporting. Symptoms are extracted using Name Entity Recognition (NER), followed by denoising with a combination of Graph Convolutional Network (GCN) and Bidirectional Encoder Representations from Transformers (BERT) model to retain only User Symptom Mentions (USM). Subsequently, symptoms are mapped to standardized medical concepts using the Unified Medical Language System (UMLS). Finally, this study conducts symptom pattern analysis and visualization to illustrate temporal changes in symptom prevalence and co-occurrence.ResultsThis study identified 191,096 self-reported COVID-19-positive cases from COVID-19-related tweets and retrospectively collected 811,398,280 historical tweets, of which 2,120,964 contained symptoms information. After denoising, 39% (832,287) of symptom-sharing tweets reflected user-related mentions. The trained USM model achieved an F1 score of 0.926. Further analysis revealed a higher prevalence of upper respiratory tract symptoms during the Omicron period compared to the Delta and wild-type periods. Additionally, there was a pronounced co-occurrence of lower respiratory tract and nervous system symptoms in the wild-type strain and Delta variant.ConclusionThis study established a robust framework for pandemic monitoring via social media, integrating denoising of user-related symptom mentions and longitudinal data. The findings underscore the importance of denoising procedures in revealing accurate prevalence trends, thereby minimizing biases in symptom analysis.
Effective coverage for maternal health: operationalizing effective coverage cascades for antenatal care and nutrition interventions for pregnant women in seven low- and middle-income countries
Authors: Sheffel Ashley , Carter Emily , Heidkamp Rebecca , Hossain Aniqa Tasnim , Katz Joanne , Kim Sunny , Lama Tsering Pema , Marchant Tanya , Perin Jamie , Requejo Jennifer ,   Global Financing Facility, World Bank, Walton Shelley , Munos Melinda K. 
Published: July 2024

AbstractBackgroundEfforts to improve maternal health have focused on measuring health and nutrition service coverage. However, high maternal mortality rates, despite improved service coverage, suggests that coverage indicators alone that do not account for quality can overestimate the health benefits of a service. Effective coverage (EC) cascades have been proposed as an approach to capture service quality within population-based coverage measures, but the proposed maternal health EC cascades have not been operationalized. This study aims to operationalize the effective coverage cascades for antenatal care (ANC) and maternal nutrition services using existing data from low- and middle-income countries (LMICs).MethodsWe used household surveys and health facility assessments from seven LMICs to estimate EC cascades for ANC and maternal nutrition services provided during ANC visits. We developed theoretical coverage cascades, defined health facility readiness and provision/experience of care scores and linked the facility-based scores to household survey data based on geographic domain and facility type. We then estimated the coverage cascade steps for each service by country.FindingsService contact coverage for at least one ANC visit (ANC1) was high, ranging from 80% in Bangladesh to 99% in Sierra Leone. However, there was a substantial drop in coverage from service contact to readiness-adjusted coverage, and a further drop to quality-adjusted coverage for all countries. For ANC1, from service contact to quality-adjusted coverage, there was an average net decline of 52 percentage points. For ANC1 maternal nutrition services, there was an average net decline of 48 percentage points from service contact to quality-adjusted coverage. This pattern persisted across cascades. Further exploration revealed that gaps in service readiness including lack of provider training, and gaps in provision/experience of care such as limited nutrition counseling were core contributors to the drops in coverage observed.ConclusionsThe cascade approach provided useful summary measures that identified major barriers to EC. However, detailed measures underlying the steps of the cascade are likely needed to support evidence-based decision-making with more actionable information. This analysis highlights the importance of understanding bottlenecks in achieving health outcomes and the inter-connectedness of service access and service quality to improve health in LMICs.
Guilt by association: Plant-based foods can be incorporated into both healthy and unhealthy plant-based diet indices associated with coronary heart disease
Authors: Jamshidi-Naeini Yasaman , Henschel Beate , Shikany James M. , Allison David B. , Brown Andrew W. 
Published: July 2024

AbstractBackgroundOne approach to test for differential associations between plant foods with health uses a scoring approach: foods categorized into animal or ‘healthy’ plant-based or ‘unhealthy’ plant-based groups to construct a plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI).ObjectiveTo evaluate robustness of associations between diet indices and incident coronary heart disease (CHD) risk when recategorizing food groups in indices.MethodsUsing REasons for Geographic and Racial Differences in Stroke (REGARDS) data, we replicated a published use of the scoring approach. Using Cox proportional hazards regression, we assessed ramifications of the following on associations between diet indices and CHD risk: 1) reconfiguring foods within and among food groups, using potatoes as an example, 2) leave-one-out analysis for each of 12 plant-based food groups, and 3) agnostically redefining each food group as ‘healthy’ or ‘unhealthy’.ResultsOver 153,286 person-years of follow-up, there were 868 cases of CHD. Replication analyses did not reach statistical significance. General patterns of magnitude of hazard ratios (HRs) in replication and reconfiguration models were PDI HRs < hPDI HRs < uPDI HRs for women, and hPDI < PDI < uPDI for men. Five models reconfiguring potatoes resulted in small, varied differences in PDI, hPDI, and uPDI associations. Leave-one-out analyses resulted in greater variation of associations between indices and CHD. In agnostic models, each plant-based food group was classified in indices as ‘healthy’ and ‘unhealthy’ with statistically significant beneficial or deleterious associations with CHD. Averaged over 4,096 models, HRs’ shifts were small when food groups were moved between ‘healthy’ and ‘unhealthy’.ConclusionStatistically significant associations between hPDI, uPDI, and PDI and incident CHD were not replicated. Small perturbations of the scoring approach had varied impacts on HRs. Agnostically constructing diet indices demonstrated the potential for guilt (or benefit) by association: any of the food groups we studied could be categorized with others in an index showing beneficial or deleterious associations.
Cell membrane glycan contents are biochemical factors that constitute a kinetic barrier to viral particle uptake in a protein-nonspecific manner
Authors: Kaizuka Yoshihisa , Machida Rika 
Published: July 2024

AbstractVarious types of glycoproteins have been suggested to inhibit viral infection of cells via steric repulsion. However, it is difficult to evaluate such physical actions genetically, simply because they are nonspecific and can be caused by any molecule. Therefore, we investigated a method to compare this nonspecific action among cells with diverse membrane protein profiles. We found that a wide range of glycoproteins individually had a strong inhibitory effect on infection, while on the other hand, the total amount of glycans was negatively correlated with the infection level in each cell. Thus, the infection-inhibitory effect of glycoproteins was molecularly nonspecific, but was additively enhanced according to the amount of glycans on the cell surface. In this correlation, glycans function as a fundamental factor. Further investigating the mechanism by which glycans function as a factor in infection control, we conclude that the repulsion between proteins created by branched glycans forms a kinetic energy barrier against packing the virus into the region of protein interstitial space. As a result, the formation of the adhesive interface between the virus and the cell membrane, which is necessary for infection, is inhibited. This study attempted to link the cell’s nonspecific physical properties with intracellular biochemicals. A similar approach may be applied to quantify other nonspecific biological phenomena.
Quiescent cells maintain active degradation-mediated protein quality control requiring proteasome, autophagy and nucleus-vacuole junctions
Authors: Franić Dina , Pravica Mihaela , Zubčić Klara , Miles Shawna , Bedalov Antonio , Boban Mirta 
Published: July 2024

AbstractMany cells spend a major part of their life in quiescence, a reversible state characterized by a distinct cellular organization and metabolism. In glucose-depleted quiescent yeast cells, there is a metabolic shift from glycolysis to mitochondrial respiration, and a large fraction of proteasomes are reorganized into cytoplasmic granules containing disassembled particles. Given these changes, the operation of protein quality control (PQC) in quiescent cells, in particular the reliance on degradation-mediated PQC and the specific pathways involved, remains unclear. By examining model misfolded proteins expressed in glucose-depleted quiescent yeast cells, we found that misfolded proteins are targeted for selective degradation requiring functional 26S proteasomes. This indicates that a significant pool of proteasomes remains active in degrading quality control substrates. Misfolded proteins were degraded in a manner dependent on the E3 ubiquitin ligases Ubr1 and San1, with Ubr1 playing a dominant role. In contrast to exponentially growing cells, the efficient clearance of certain misfolded proteins additionally required intact nucleus-vacuole junctions (NVJ) and Cue5-independent selective autophagy. Our findings suggest that proteasome activity, autophagy, and NVJ-dependent degradation operate in parallel. Together the data demonstrate that quiescent cells maintain active PQC that relies primarily on selective protein degradation. The necessity of multiple degradation pathways for the removal of misfolded proteins during quiescence underscores the importance of misfolded protein clearance in this cellular state.
Elucidating the Transport Mechanisms and Metabolic Roles of Serine, Threonine, and Glycine inTrypanosoma cruzi
Authors: Alencar Mayke Bezerra , Bruno Moreira Girard Richard Marcel , Crispim Marcell , Baptista Carlos Gustavo , Biran Marc , Bringaud Frederic , Silber Ariel Mariano 
Published: July 2024

ABSTRACTl-Serine (l-Ser) andl-Threonine (l-Thr) have versatile roles in metabolism. In addition to their use in protein synthesis, these amino acids participate in the biosynthesis pathways of other amino acids and even phospholipids. Furthermore,l-Ser andl-Thr can be substrates for a Ser/Thr dehydratase (Ser/ThrDH), resulting in pyruvate (Pyr) and 2-oxobutyrate, respectively, thus being amino acids with anaplerotic potential.Trypanosoma cruzi, the etiological agent of Chagas disease, uses amino acids in several biological processes: metacyclogenesis, infection, resistance to nutritional and oxidative stress, osmotic control, etc. In this study, we investigated the import and metabolism ofl-Ser,l-Thr, and Gly inT. cruzi. Our results demonstrate that these amino acids are transported from the extracellular environment intoT. cruzicells through a saturable transport system that fits the Michaelis-Menten model. Our results show thatl-Ser andl-Thr can sustain epimastigote (Epi) cell viability under nutritional stress (NS) conditions and can stimulate oxygen consumption to maintain intracellular ATP levels. Additionally, our findings indicate thatl-Ser plays a role in establishing the mitochondrial membrane potential (ΔΨm) inT. cruzi.l-Ser is also involved in energy metabolism via the Ser-Pyr pathway, which stimulates the production and subsequent excretion of acetate and alanine. Our results demonstrate the importance ofl-Ser andl-Thr in the energy metabolism ofT. cruziand provide new insights into the metabolic adaptations of this parasite during its life cycle.
Colicin Receptor CirA EnhancesSalmonellaTyphimurium’s Resistance to Colicin Ib in the Absence of the Cognate Immunity Protein
Authors: Gollan BC , Luo L , Li Yan , Clark-Corrigall J , Qadri B , Alshuwaier A , Hinton J , Khan CMA 
Published: July 2024

AbstractIntestinal microbiota play a central role in colonisation resistance providing a fundamental barrier to infection to enteric pathogens. An important mechanism of colonisation resistance involves the production of antimicrobial peptides, such as colicins. Pore-forming colicins, synthesised byEscherichia coli(E. coli) strains, target competing bacteria in their environmental niche, whilst the producing cells are safeguarded by specific immunity proteins. Notably, non-typhoidalSalmonellaTyphimurium strains can produce a narrow-spectrum protein toxin colicin IB (ColIb) providing a competitive edge against susceptibleEnterobacteriaceaestrains. However, the multi-drug resistant and systemically invasive iNTS (invasive non-TyphoidalSalmonella)S. Typhimurium D23580 strain poses an interesting case. The strain lacks colicin Ib production and the corresponding immunity protein, but its potential vulnerability in a colicin-rich gastrointestinal milieu remains uninvestigated. In this study,S. Typhimurium D23580 exhibited resistance to colicin Ib under tested conditions, despite the absence of the immunity geneimm. Intriguingly, in colicin Ib-producingS. Typhimurium strains, theimmgene appeared functionally redundant in contrast to our current understanding. ColIb binds to the outer membrane protein CirA and is translocated to the inner membrane where it forms a pore in sensitive bacteria dissipating the electrochemical potential. Through a series of experimental approaches, including the use ofEscherichia coliandS. TyphimuriumcirAdeletion mutants, promoter-swap techniques, and gene complementation, we identified that the colicin resistance phenotype inS. Typhimurium was partly attributable to the CirA receptor. This finding suggests a complex interplay in the microbial resistance to colicins, highlighting the intricacies of microbial interactions within the gastrointestinal environment.
Care delivery in the context of district mental healthcare plans (DMHP) in Ghana: experiences of primary health care workers and service users
Authors: Sakyi L , Ae-Ngibise KA , Adwan-Kamara L , Weobong Ben , Lund Crick 
Published: July 2024

AbstractBackgroundThe integration of mental healthcare into primary healthcare services is an effective way to addressing the substantial treatment gap for mental health conditions in low- and middle-income (LMIC) countries. In Ghana, District Mental Healthcare Plans (DMHPs) were developed and implemented in three districts over a 2-year period. This study aimed to explore the perceptions and experiences of mental health service users and primary healthcare workers regarding the implementation of the DMHPs.MethodsThe study employed a qualitative design involving in-depth interviews with 32 service users and 28 primary healthcare providers in the three demonstration districts. Participants were purposively sampled. Interview data were analysed using reflexive thematic analysis combining inductive and deductive approaches.ResultsThree main themes were identified: 1) Factors supporting DMHP implementation, including capacity building, collaboration, awareness creation, and acceptability; 2) Challenges impacting DMHP implementation, such as inadequate resources and medication shortages; and 3) Impacts of the DMHPs, including improved access to care, reduced relapse, enhanced daily functioning, and reduced stigma. Some district-level variations were noted in the intensity of challenges and impacts.ConclusionThe DMHPs showed promise in improving mental healthcare in primary care settings in Ghana. However, addressing resource constraints and medication shortages, and sustaining capacity building and awareness creation efforts, will be crucial for successful scale-up. The perspectives of service users and healthcare providers offer valuable insights for policy makers and practitioners aiming to enhance integrated mental healthcare.Strengths and limitations of this study⇒ This study is the first in Ghana to explore in-depth the experiences of healthcare workers and service users in implementation of DMHPs.⇒ Using qualitative design provide more nuanced understanding of factors supporting implementation of DMHP which would have been more difficult to do using quantitative methods.⇒ The study reported from a relatively small sample size from only 3 districts from 261 districts in Ghana. While this sample size provided valuable insights, it may not cover the wide and diverse experiences of healthcare workers and service users involved in the DMHPs.
Single-cell analysis of human diversity in circulating immune cells
Authors: Kock Kian Hong , Tan Le Min , Han Kyung Yeon , Ando Yoshinari , Jevapatarakul Damita , Chatterjee Ankita , Lin Quy Xiao Xuan , Buyamin Eliora Violain , Sonthalia Radhika , Rajagopalan Deepa , Tomofuji Yoshihiko , Sankaran Shvetha , Park Mi-So , Abe Mai , Chantaraamporn Juthamard , Furukawa Seiko , Ghosh Supratim , Inoue Gyo , Kojima Miki , Kouno Tsukasa , Lim Jinyeong , Myouzen Keiko , Nguantad Sarintip , Oh Jin-Mi , Rayan Nirmala Arul , Sarkar Sumanta , Suzuki Akari , Thungsatianpun Narita , Venkatesh Prasanna Nori , Moody Jonathan , Nakano Masahiro , Chen Ziyue , Tian Chi , Zhang Yuntian , Tong Yihan , Tan Crystal T.Y. , Tizazu Anteneh Mehari ,   SG10K_Health Consortium, Loh Marie , Hwang You Yi , Ho Roger C , Larbi Anis , Ng Tze Pin , Won Hong-Hee , Wright Fred A. , Villani Alexandra-Chloé , Park Jong-Eun , Choi Murim , Liu Boxiang , Maitra Arindam , Pithukpakorn Manop , Suktitipat Bhoom , Ishigaki Kazuyoshi , Okada Yukinori , Yamamoto Kazuhiko , Carninci Piero , Chambers John C. , Hon Chung-Chau , Matangkasombut Ponpan , Charoensawan Varodom , Majumder Partha P. , Shin Jay W. , Park Woong-Yang , Prabhakar Shyam 
Published: July 2024

SummaryLack of diversity and proportionate representation in genomics datasets and databases contributes to inequity in healthcare outcomes globally1,2. The relationships of human diversity with biological and biomedical phenotypes are pervasive3, yet remain understudied, particularly in a single-cell genomics context. Here we present the Asian Immune Diversity Atlas (AIDA), a multi-national single-cell RNA-sequencing (scRNA-seq) healthy reference atlas of human immune cells. AIDA comprises 1,265,624 circulating immune cells from 619 healthy donors and 6 controls, spanning 7 population groups across 5 countries. AIDA is one of the largest healthy blood datasets in terms of number of cells, and also the most diverse in terms of number of population groups. Though population groups are frequently compared at the continental level, we identified a pervasive impact of sub-continental diversity on cellular and molecular properties of immune cells. These included cell populations and genes implicated in disease risk and pathogenesis as well as those relevant for diagnostics. We detected single-cell signatures of human diversity not apparent at the level of cell types, as well as modulation of the effects of age and sex by self-reported ethnicity. We discovered functional genetic variants influencing cell type-specific gene expression, including context-dependent effects, which were under-represented in analyses of non-Asian population groups, and which helped contextualise disease-associated variants. We validated our findings using multiple independent datasets and cohorts. AIDA provides fundamental insights into the relationships of human diversity with immune cell phenotypes, enables analyses of multi-ancestry disease datasets, and facilitates the development of precision medicine efforts in Asia and beyond.