bluuebunny/crossref_metadata_2025_split huggingface dataset:
Charge distribution and helical content tune the binding of septin’s amphipathic helix domain to lipid membranes
Authors: Edelmaier Christopher J. , Klawa Stephen J. , Mofidi S. Mahsa , Wang Qunzhao , Bhonge Shreeya , Vogt Ellysa J. D. , Curtis Brandy N. , Shi Wenzheng , Hanson Sonya M. , Klotsa Daphne , Forest M. Gregory , Gladfelter Amy S. , Freeman Ronit , Nazockdast Ehssan 
Published: July 2024

ABSTRACTSeptins are a class of cytoskeletal proteins that preferentially bind to domains of micron-scale curvature on the cell membrane. Studies have shown that amphipathic helix (AH) domains in septin oligomers are essential for septin curvature sensing. Yet, the underlying mechanochemical interactions that modulate this curvature sensing remain ambiguous. Here we use all-atom molecular dynamics alongside a metadynamics enhanced sampling approach to bridge the gap between time and length scales required to optimize and validate experimental design of amphipathic helices. Simulations revealed that the local charge on the termini of an 18-amino-acid AH peptide impacts its helical content and positioning within lipid membranes. These computational observations are confirmed with experiments measuring the binding of synthetic AH constructs with variable helical content and charged termini to lipid vesicles. Taken together, these results identify the helical content of amphipathic helices as a regulator of septin binding affinity to lipid membranes. Additionally, we examined an extended AH sequence including 8 amino acids upstream and downstream of the minimal 18-amino-acid-long AH domain to more closely mimic the native protein in simulations and experiments. Simulations and experiments show that the extended peptide sequence adopts a strong alpha-helical conformation when free in solution, giving rise to a higher affinity to lipid membranes than that of the shorter AH sequence. Together, these results provide insight into how the native septin proteins interact with membranes, and establish general design principles that can guide the interaction of future synthetic materials with lipid membranes in a programmable manner.STATEMENT OF SIGNIFICANCEUnderstanding how cells sense and react to their shape is necessary for numerous biological processes. Here we explore the interactions between amphipathic helices, a curvature sensing protein motif, and lipid membranes. Using molecular dynamics simulations, enhanced simulation sampling techniques, and experiments, we find that increasing the helical content of the amphipathic helix or adding charged capping sequences yields higher membrane binding affinity. Understanding these parameters for membrane-binding could enable us to interface and regulate native protein functions, as well as guide the design of synthetic curvature-sensing materials that can interact with and deform lipid membranes.
Characterization ofDnajc12knock-out mice, a model of hypodopaminergia
Authors: Deng Isaac Bul , Follett Jordan , Fox Jesse D. , Wall Shannon , Farrer Matthew J. 
Published: July 2024

AbstractHomozygousDNAJC12c.79-2A>G (p. V27Wfs*14) loss-of-function mutations were first reported as a cause of young-onset Parkinson’s disease. However, bi-allelic autosomal recessive pathogenic variants inDNAJC12may lead to an alternative constellation of neurological features, including infantile dystonia, developmental delay, intellectual disability and neuropsychiatric disorders. DNAJC12 is understood to co-chaperone aromatic amino acid hydroxylases to foster the synthesis of biogenic amines.In vitro, we discover overexpressed DNAJC12 forms a complex with guanine triphosphate cyclohydrolase 1 (GCH1), the rate-limiting enzyme in the synthesis of tetrahydrobiopterin, a cofactor paramount for biogenic amines synthesis. We also confirm DNAJC12’s interaction with tyrosine (TH) and tryptophan hydroxylase (TPH), which are rate-limiting enzymes for synthesis of biogenic amines dopamine (DA) and serotonin (5-HT).In-vitroknock-down of DNAJC12 with a siRNA destabilizes the DNAJC12-TH-GCH1 complex, reducing GCH1 levels, whereas reciprocal overexpression of both TH and GCH1 increases endogenous DNAJC12, alluding to the significance of modulating the DNAJC12-TH-GCH1 complex as a therapy for DNAJC12 and other biogenic amine disorders. We extend these investigations to a Cre-conditional knock-out mice (cDKO) in which loxP sites flankingDnajc12exon 2 enable its excision by cre-recombinase. With germline Cre expression, we have created a constitutiveDnajc12knock-out (DKO). DKO mice exhibit reduced locomotion/ exploratory behavior at 3 months in automated open-field testing, accompanied by increased plasma phenylalanine which is a cardinal feature of patients with pathogenicDNAJC12variants. In striatal tissue, total DA and 5-HT, their metabolites, and electrically-evoked DA release are all reduced. Biochemical alterations in synaptic proteins are also apparent, with enhanced phosphorylation of Th pSer31 and pSer40 reflecting biological compensation. Most immediately, cDKO and DKO mice present models to develop and refine therapeutic approaches for biogenic amines disorders, including dystonia and parkinsonism. They will also enable the pleiotropic functions of biogenic amines (including DA), usually synthesized in the brain or periphery, to be separated.
Assessment of variant effect predictors unveils variants difficulty as a critical performance indicator
Authors: Radjasandirane Ragousandirane , Diharce Julien , Gelly Jean-Christophe , de Brevern Alexandre G. 
Published: July 2024

AbstractAmino acid substitutions in protein sequences are generally harmless, but a certain number of these changes can lead to disease. Accurate prediction of the impact of genetic variants is crucial for clinicians as it accelerates the diagnosis of patients with missense variants associated with health issues. Numerous computational tools have been developed for prediction of the pathogenicity of genetic variants based on different methodologies. Nowadays, many approaches are based on Machine Learning. Assessment of the performance of these diverse computational tools is crucial to provide guidance to both future users and especially clinicians. In this study, a large-scale study of 65 tools was conducted. Variants from both clinical and functional context have been used, incorporating data from the ClinVar database and bibliographic sources. The analysis showed that AlphaMissense is often performing very well and is actually the best option among existing tools. Additionally, meta-predictors, as expected, are of high quality and perform well on average. Tools using evolution information demonstrated highest performances on functional variants. These results also highlighted some variations in the difficulty to predict some specific variants while others are always well categorized. Strikingly, the majority of variants from the ClinVar database appear to be easy to predict, while variants from other sources of data are more challenging. These results demonstrate that this variant predictability can be classified into three distinct classes: easy, moderate and hard to predict. We analyzed the parameters leading to these differences and show that classes are linked to structural and functional information.
Disentangling the causal effects of education and participation bias on Alzheimer’s disease using Mendelian Randomization
Authors: Chatterjee Aadrita , Cavaillès Clémence , Davies Neil M , Yaffe Kristine , Andrews Shea J 
Published: July 2024

AbstractIntroductionPeople with university degrees have a lower incidence of Alzheimer’s Disease (AD). However, the relationship between education and AD could be due to selection, collider, and ascertainment biases, such as lower familiarity with cognitive testing or the fact that those with degrees are more likely to participate in research. Here, we use two-sample Mendelian randomization (MR) to investigate the causal relationships between education, participation, and AD.MethodWe used genome-wide association study (GWAS) summary statistics for educational attainment, three different measures of participation, AD (clinically diagnosed AD), and AD/ADRD (clinical diagnosis and family history of AD and related dementias). Independent genome-wide significant single nucleotide polymorphisms (SNPs) were extracted from the exposure summary statistics and harmonized with the outcome SNPs. Fixed-effects inverse variance weighted meta-analysis was the primary MR method; Cochran’s Q statistic and MR Egger intercept were used to test for heterogeneity and pleiotropy, and Radial-MR was used to identify outliers. Sensitivity analyses included MR Egger, Weighted Median, and Weighted mode. Bidirectional analyses were used to test if AD pathology affects participation and multivariable MR (MVMR) assessed independent exposure-outcome effects.ResultsEducational attainment reduced the risk of AD (ORIVW95% CI= 0.70 [0.63, 0.79], p = 8e-10), and the results were robust based on sensitivity analyses. However, education increased the risk of AD/ADRD, though the results were not robust to sensitivity analyses (ORIVW95% CI= 1.09 [1.02, 1.15], p = 0.006). Participation in MHQ reduced the odds of AD (ORIVW95% CI= 0.325 [0.128, 0.326], p = 0.01). When adjusting for participation in MVMR, education remained associated with a reduced risk of AD (ORIVW95% CI= 0.76 [0.62, 0.92], p = 0.006).ConclusionUnivariate MR analyses indicated that education and participation reduced the risk of AD. However, MR also suggested that education increased the risk of AD/ADRD, highlighting the inconsistencies between clinical and proxy diagnoses of AD, as proxy-AD may be affected by selection, collider, or ascertainment bias. MVMR indicated that participation is unlikely to explain the effect of education on AD identified in MR, and the protective effect of educational attainment may be due to other biological mechanisms, such as cognitive reserve.
Perceived changes in competence, relatedness, and autonomy reported by mothers since joining a mom-centered digital community
Authors: McManus-Shipp Katherine E. , Field Christiana M. , Bhusal Sandesh , Dennis Cindy-Lee , Waring Molly E. 
Published: July 2024

AbstractBackgroundMotherhood can profoundly challenge individuals’ well-being. Social media and other digital platforms are promising modalities for reaching and supporting mothers with evidence-based psychoeducation and connection to peers. However, much is unknown about how mothers perceive these online peer communities and their impact on health and well-being.PurposeTo describe mothers’ perceptions of the impact of exposure to and engagement with a mom-centered digital community (Momwell) on their well-being.MethodsPregnant persons and mothers exposed to Momwell psychoeducational content and community related to motherhood via social media, podcast, or blog completed an online survey (N=569). Participants reported several perceived changes related to competence, relatedness/connection, and autonomy in decision-making since joining the Momwell community by rating their agreement with a series of questions.ResultsAll but two participants identified as mothers; 45% were either pregnant or within 12 months postpartum. The majority agreed with statements about perceived changes in their lives, well-being, and feelings since joining the Momwell community (82-97%). All participants reported positive changes related to their sense of competence, 99% reported positive changes related to relatedness, and 97% reported positive changes related to autonomy.ConclusionExposure to psychoeducational content related to motherhood and maternal mental health and peer engagement within a mom-centered community can enhance maternal well-being through positive changes in competence, relatedness, and autonomy.
Df-1 Cell Adaptation and Immune Responses of Lc-75 Vaccinal Strain ofInfectious Bursal Disease Virusin Chicken
Authors: Abate Fentahun Mitku , Ali Destaw Asfaw , Getachew Belayneh , Mohammed Hawa 
Published: July 2024

ABSTRACTThe currentInfectious bursal disease virus(IBDV) vaccine strain of LC-75 in Ethiopia is being produced through chicken embryo fibro blast cell which has short lifespan and limited need of specific pathogen free eggs. Ideally, vaccine should have better longevity and being effective in cost and time. Experimental research was conducted to adopt DF-1 cell and to validate the immune responses, immunosuppressive effect and immunogenicity tests, of LC-75 vaccinal strain ofInfections bursal diseases virusA total of 76 chickens were used for these experiments. The seroconversion rate of the vaccine were measured using haemaglutination inhibition (HI) test in the vaccinated two experiment groups, adapted IBDV and Newcastle vaccines at two weeks interval for the first group and only Newcastle vaccine for the second experiment groups. To perform the immunogenicity test, two groups having 20 chickens per group were used and samples of serum were taken on 0-, 7-, 14- and 28-days post vaccinations and subjected to indirect ELISA test. The group that received both vaccine types produced haemagglutination inhibition titer (HIT) of 97.33±22.49 whereas the other group that received only Newcastle vaccine produced 124±24.92. The control group always showed no detectable antibody while the vaccinated group was able to produce average antibody S/P values of 0.00 ± 0.01 at day 0, 0.02± 0.01 at day 7, 1.05±0.10 at day 14 and 0.83±0.05 at day 28. RT-PCR using a 400 bp IBDV viral protein 2(VP2) specific primer resulted from positive bands in all samples. In conclusion, the vaccinal strain was able to replicate and adapt on the DF-1 cells and it was found to be immunogenic as well as less immunosuppressive.
A dendritic substrate for temporal diversity of cortical inhibition
Authors: Morabito Annunziato , Zerlaut Yann , Dhanasobhon Dhanasak , Berthaux Emmanuelle , Tzilivaki Alexandra , Moneron Gael , Cathala Laurence , Poirazi Panayiota , Bacci Alberto , DiGregorio David , Lourenço Joana , Rebola Nelson 
Published: July 2024

AbstractIn the mammalian neocortex, GABAergic interneurons (INs) inhibit cortical networks in profoundly different ways. The extent to which this depends on how different INs process excitatory signals along their dendrites is poorly understood. Here, we reveal that the functional specialization of two major populations of cortical INs is determined by the unique association of different dendritic integration modes with distinct synaptic organization motifs. We found that somatostatin (SST)-INs exhibit NMDAR-dependent dendritic integration and uniform synapse density along the dendritic tree. In contrast, dendrites of parvalbumin (PV)-INs exhibit passive synaptic integration coupled with proximally enriched synaptic distributions. Theoretical analysis shows that these two dendritic configurations result in different strategies to optimize synaptic efficacy in thin dendritic structures. Yet, the two configurations lead to distinct temporal engagement of each IN during network activity. We confirmed these predictions within vivorecordings of IN activity in the visual cortex of awake mice, revealing a rapid and linear recruitment of PV-INs as opposed to a long-lasting integrative activation of SST-INs. Our work reveals the existence of distinct dendritic strategies that confer distinct temporal representations for the two major classes of neocortical INs and thus dynamics of inhibition.
Nutritional Status and Lifestyle of Children in Orphanages and Middle-Class Families in Khulna City, Bangladesh: A Cross-Sectional Study
Authors: Safa Tohora , Alvi Mir Fhamid Ahsan , Mahazabin Maliha 
Published: July 2024

AbstractThe lack of biological parents has a significant effect on a child’s growth and overall welfare. This study examines the circumstances of children living in orphanages where one or both parents have passed away, as well as children from middle-class households. The main focus is on their lifestyle, nutritional status, and well-being. We performed a chi-square test and descriptive analysis to establish a correlation. Our research revealed that orphaned children in the orphanage tend to mostly consume carbohydrate-rich foods in their diet. Inadequate access to nourishing food can impede their capacity to sustain optimal physical and mental well-being. Furthermore, the absence of recreational amenities in the orphanage may impede their mental well-being, as they already experience psychological challenges due to the absence of parental affection. Children from middle-class households are often exposed to a significant amount of unhealthy fast food and bakery items. This practice should be discontinued in order to promote a healthier society.
Clinical, immune and genetic risk factors of malaria-associated acute kidney injury in Zambian Children: A study protocol
Authors: Mwaba Chisambo , Munsaka Sody , Mwakazanga David , Rutagwerae David , Ngalamika Owen , Mwanza Suzanna , McCulloch Mignon , Mpabalwani Evans 
Published: July 2024

AbstractBackgroundAcute kidney injury (AKI) affects nearly half of children with severe malaria and increases the risk of adverse outcomes such as death and poor cognitive function. The pathogenesis and predictors of malaria-associated acute kidney injury (MAKI) are not fully described. This study aims to determine the clinical, immune, and genetic correlates of risk to AKI in Zambian children admitted with malaria. In addition, we intend to assess a modified renal angina index (mRAI), kidney injury molecule – 1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL)) and soluble urokinase receptor (suPAR), when done on the first day of admission, for ability to predict AKI 48 hours later (day 3) in children admitted with malaria.MethodsThis is an unmatched case-control study, with a case to control ratio of 1:1, in which 380 children with malaria and aged less than 16 years are being recruited from two hospitals in Zambia. Eligible children are recruited after obtaining written informed consent. Recruitment began 6thMarch,2024 and will continue until July 2025. AKI is defined using the 2012 KIDGO AKI creatinine criteria and cases are defined as children admitted with malaria who develop AKI within 72 hours of admission while controls are children admitted with malaria but with no AKI. Serum creatinine is collected on day 1 within 24hours of admission and then again on Day 3 post admission. Baseline biomarker concentrations will be determined using the Luminex multiplex Elisa system or high-sensitivity ELISA. SPSS version 29 will be used for data analysis. Descriptive statistics and inferential statistical tests will be run as appropriate. A p ≤ 0.05 will be considered as significant. The utility of the renal angina score for predicting MAKI will be assessed using sensitivity, specificity, and estimates of the area under the curve (AUC).
Modeling the
γ
spectrum from
d−t
collisions
Authors: Timofeyuk N. K. , Bailey G. W. , Gilbert M. R. 
Published: July 2024

Motivated by possible industrial fusion applications of spectroscopy of the γ rays accompanying d−t collisions we develop the first model calculations of the minor branching ratio of the d+t reaction, d+t→α+n+γ. The model exploits the most relevant physics feature—spin conservation in electric dipole transitions—which leads to a peculiar mechanism of this reaction: γ emission via bremsstrahlung from an intermediate α−n state. We highlight that, as a consequence of the bremsstrahlung, the γ spectrum contains nonzero contributions at all energies, thus making inclusive dtγ cross section measurements sensitive to the low-energy cutoff of the detected γ events. Comparison of our predictions to existing d+t→α+n+γ measurements in accelerators, employing cutoffs of 13 and 14 MeV, and inertial confinement fusion facilities, with a low-limit cutoff of 0.4 to 10 MeV, suggests a possible contradiction between results from these two types of experiments. Our predictions agree well with accelerator measurements and corroborate the cutoff dependence observed in inertial confinement experiments. These predictions are sensitive to the wave function details inside the short-range area of the α−n interaction, with uncertainty comparable to that of available experimental data, but become model independent below 4–5 MeV. This part of the γ spectrum features a previously unexpected rise, which below 0.5 MeV surpasses the main 17-MeV γ peak in strength. The reactivity of the d+t→α+n+γ branch was found to be proportional to its cross section. It strongly depends on the d−t plasma temperature, which opens the possibility of not only total d+t reactivity measurements but also advanced plasma temperature diagnostics.

Published by the American Physical Society
2024
Investigating the impact of digital health technology adoption on female physicians’ work–life balance in Bahrain
Authors: Alharoon Sharifah , Aldhmour Fairouz M. 
Published: July 2024

Purpose
This study aims to examine the impact of digital health technology adoption on female physicians’ work–life balance (WLB) in Bahrain. This study also examines the impact of two moderating variables: career stage, based on the kaleidoscope career model (KCM) and the presence of domestic workers, based on Becker’s theory of the allocation of time.

Design/methodology/approach
An electronic quantitative survey was administered to female physicians working in Bahrain. The survey gathered data on various aspects of digital health technology, WLB and demographic characteristics such as age and the presence of domestic workers. From a target population of approximately 1,000 female physicians in Bahrain, 102 participated in the survey.

Findings
The authors found that the effect of digital health technologies on WLB is positive in general and specifically for the early-career stage; however, it harms WLB in the middle and late-career stages. This is consistent with KCM predictions. In addition, there is no moderating effect of having domestic helpers.

Originality/value
This paper contributes to the theoretical understanding of the effect of technology on WLB by expanding the traditional model (KCM) to include an economic model of how female physicians allocate their time between work and home responsibilities, including the effect that a domestic worker can have on this allocation. Beyond these theoretical contributions, this paper is also the first to study technology and WLB in the health sector in Bahrain following the COVID-19 pandemic.
How emotions affect the outcomes of information overload: information avoidance or information consumption?
Authors: Cheng Xusen , Zhang Shuang , Yang Bo 
Published: July 2024

PurposeInformation overload has become ubiquitous during a public health emergency. The research purpose is to examine the role of mixed emotions in the influence of perceived information overload on individuals’ information avoidance intention and the state of fear of missing out.Design/methodology/approachA mixed-methods approach was used in this study: a qualitative study of 182 semi-structured interviews and a quantitative study of 309 surveys.FindingsThe results show that perceived information overload negatively affects peace of mind and positively affects fatigue and fear. Emotions with a low activation level (peace of mind and fatigue) promote emotions with a high activation level (hope and fear), and peace of mind negatively influences fatigue. Additionally, peace of mind negatively affects information avoidance intention, while hope positively affects the state of fear of missing out. These two information processing outcomes are positively impacted by fatigue and fear.Originality/valueThis study extends existing knowledge by uncovering the underlying influence of mixed emotions on individuals’ different information processing outcomes caused by perceived information overload. It provides practical insights for online media platforms and Internet users regarding how to process overwhelming information during a public health emergency.