bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenosine deficiency facilitates CA1 synaptic hyperexcitability in the presymptomatic phase of a knock in mouse model of Alzheimer’s disease
Authors: Bonzanni Mattia , Braga Alice , Saito Takashi , Saido Takaomi C. , Tesco Giuseppina , Haydon Philip G.
Published: April 2024

The disease’s trajectory of Alzheimer’s disease (AD) is associated with and worsened by hippocampal hyperexcitability. Here we show that during the asymptomatic stage in a knock in mouse model of Alzheimer’s disease (APPNL-G-F/NL-G-F; APPKI), hippocampal hyperactivity occurs at the synaptic compartment, propagates to the soma and is manifesting at low frequencies of stimulation. We show that this aberrant excitability is associated with a deficient adenosine tone, an inhibitory neuromodulator, driven by reduced levels of CD39/73 enzymes, responsible for the extracellular ATP-to-adenosine conversion. Both pharmacologic (adenosine kinase inhibitor) and non-pharmacologic (ketogenic diet) restorations of the adenosine tone successfully normalize hippocampal neuronal activity. Our results demonstrated that neuronal hyperexcitability during the asymptomatic stage of a KI model of Alzheimer’s disease originated at the synaptic compartment and is associated with adenosine deficient tone. These results extend our comprehension of the hippocampal vulnerability associated with the asymptomatic stage of Alzheimer’s disease.

Abstract Figure

Synaptic hyperexcitability spreads to the soma and manifests at low frequencies of stimulation

Synaptic hyperexcitability is associated with reduced adenosine tonein vitroandin vivo

Reduced adenosine tone is driven by reduced ATP-to-adenosine extracellular conversion

Restoration of adenosine tone successfully normalizes neuronal excitability in the AD model
Modulating Cardiac Energetics in Cardio-Metabolic Syndromes: A mechanistic, hyperpolarized MR Trial of Ninerafaxstat Treatment
Authors: Hundertmark Moritz. J. , Siu Adrienne. G. , Matthews Violet , Lewis Andrew J. , Grist James , Patel Jai , Chamberlin Paul , Sarwar Rizwan , Yavari Arash , Dehbi Hakim-Moulay , Rao Prashant , Shi Xu , Zheng Shuning , Robbins Jeremy M. , Gerszten Robert E. , Frenneaux Michael P. , Valkovič Ladislav , Miller Jack J.J.J , Neubauer Stefan , Tyler Damian J. , Rider Oliver J.
Published: April 2024

Background

Type 2 diabetes (T2D) and obesity are key contributors for heart failure (HF)- development, especially for HF with a preserved ejection fraction (HFpEF). On a molecular basis, excessive use of fatty acids (FA) induces lipotoxicity which in turn promotes inflammation, reduces mitochondrial pyruvate dehydrogenase (PDH) activity and impairs myocardial energetics and -function. Harnessing in-vivo, real time measurement of cellular metabolism via hyperpolarized pyruvate MR, we aimed to assess the effects of ninerafaxstat, a selective FA oxidation inhibitor, on cardiac energetics, metabolism & diastolic function in patients with cardio-metabolic syndromes.

Methods

IMPROVE-DiCE was an open-label, mechanistic phase 2a trial. 21 participants received 200mg ninerafaxstat twice daily for four (n=5) or eight weeks (n=16). Myocardial energetics (phosphocreatine to adenosine triphosphate ratio, PCr/ATP), metabolism and function were assessed pre-& post-treatment using magnetic resonance imaging (MRI),31P- and1H-MR spectroscopy (MRS). We utilised hyperpolarized [1-13C]pyruvate MRS to assess in-vivo PDH-flux (n=9) and plasma metabolomics and proteomics to assess whole body metabolism.

Results

Patients presented with impaired PCr/ATP, (median 1.6 [IQR 1.4, 2.1]), myocardial steatosis (2.2 % [IQR 1.5, 3.2]) and LV diastolic dysfunction (peak circumferential diastolic strain rate 0.86/s [IQR 0.82, 1.06]) at baseline. Ninerafaxstat treatment improved myocardial energetics by 32% (p<0.01), reduced myocardial triglyceride content by 34% (p=0.03) and showed a trend towards improved PDH-flux (mean 45% increase,p=0.08). Diastolic function was significantly improved post-treatment (peak diastolic strain rate by 10%, peak LV filling rate by 11%, bothp<0.05).

Conclusions

Metabolic modulation with ninerafaxstat significantly improved myocardial energetics, reduced myocardial steatosis and improved LV diastolic filling. Combining hyperpolarized MRS and metabolomics, is a powerful approach to examine the mechanism of action of novel metabolic modulators.

REGISTRATION

URL:https://clinicaltrials.gov;Unique identifier:NCT04826159

Abstract Figure
HIV and Pregnancy among Adolescents in Sub-Saharan Africa: A Scoping Review
Authors: Akinsolu Folahanmi Tomiwa , Adewole Ifeoluwa Eunice , Lawale Abisola , Olagunju Mobolaji Timothy , Abodunrin Olunike Rebecca , Ola Oluwabukola Mary , Chukwuemeka Abel Nnamdi , Gambari Aisha Oluwaseun , Eleje George Uchenna , Ezechi Oliver Chukwujekwu
Published: April 2024

The interaction of adolescent pregnancy with HIV is a complex and crucial public health issue worldwide. This is evident in sub-Saharan Africa, where the co-occurrence of HIV and adolescent pregnancies represents a high risk for additional health and social consequences for both adolescent mothers and their children. This study aims to explore literature to provide a clear synthesis of data related to pregnancies among adolescents living with HIV in Sub-Saharan Africa.

A literature search was conducted in July 2023 using PubMed, Scopus, CINAHL, Cochrane Library, African Journals Online, and World Health Organization Global Index Medicus. Two authors screened potential studies. Articles selected were those published in or translated into the English language between 2002 and 2022.

Among 1,560 identified results, 25 peer-reviewed publications on pregnancy among adolescents living with HIV in Sub-Saharan Africa were included after screening. The studies, included both qualitative and quantitative data, with a total of 178,227 participants in the age range of 12-18 years. The majority of the studies reported quantitative data, while a few presented qualitative or mixed-methods findings.

This scoping review highlights disparities in pregnancy prevalence, revealing varied rates among different age groups. The underrepresentation of adolescents in demographic studies suggests diverse vulnerabilities and access to healthcare. The study also emphasizes the need for tailored healthcare services and comprehensive interventions addressing HIV risk, mental health challenges, and socio-economic barriers.
Automating Responses to Patient Portal Messages Using Generative AI
Authors: Kaur Amarpreet , Budko Alex , Liu Katrina , Eaton Eric , Steitz Bryan , Johnson Kevin B.
Published: April 2024

Background

Patient portals serve as vital bridges between patients and providers, playing an increasing role in healthcare communication. The rising volume and complexity of these messages is exacerbating physician and nursing burnout. Recent studies have demonstrated that AI chatbots can generate message responses that are viewed favorably by healthcare professionals; however, these studies have not included the diverse range of messages typically found in patient portals. Our goal is to investigate the quality of GPT-generated message responses across the spectrum of message types within a patient portal.

Methods

We used novel prompt engineering techniques to craft synthetic responses tailored to adult primary care patients. We enrolled a sample of primary care providers in a cross-sectional study to compare authentic with synthetic patient portal message responses, generated by GPT-4. The survey assessed each message’s empathy, relevance, medical accuracy, and readability on a scale from 0 to 5. Respondents were asked to identify messages that were GPT-generated vs. provider-generated. Mean scores for all metrics were computed for subsequent analysis.

Results

A total of 49 health care providers participated in the survey (59% completion rate), comprising 16 physicians and 32 advanced practice providers (APPs). When presented with GPT vs. authentic message response pairs, participants correctly identified GPT-generated responses 73% of the time and correctly identified authentic responses 50% of the time. In comparison to messages generated by physicians, GPT-4 generated messages exhibited higher mean scores for empathy (3.57 vs. 3.07, p < 0.001), relevance (3.94 vs. 3.81, p = 0.08) accuracy (4.05 vs. 3.95, p= 0.12) and readability (4.5 vs. 4.13, p < 0.001).

Limitations

The study is a single site, single-specialty study, limited due to the use of synthetic data.

Conclusion

Our findings affirm the potential of GPT-generated patient portal message responses to achieve comparable levels of empathy, relevance, and readability to those found in typical responses according to the health care providers and indicates promising prospects for their integration in the healthcare sector. Additional studies should be done within provider workflows and with careful evaluation of patient attitudes and concerns related to the ethics as well as the quality of generated patient portal message responses in all settings.
Evaluating the causal relationships between urate, blood pressure, and kidney function in the general population: a two-sample Mendelian Randomization study
Authors: Tang Haotian , Walker Venexia M , Gaunt Tom R
Published: April 2024

Background

Associations between blood urate levels, blood pressure (BP), and kidney function have previously been reported in observational studies. However, causal inference between these three traits is challenging due to potentially bidirectional relationships. Method: We applied bidirectional univariable Mendelian randomization (UVMR) to assess the causal relationships between urate levels, BP, and kidney function, proxied by estimated glomerular filtration rate (eGFR), using genetic associations from UK Biobank and CKDGen. We performed multivariable MR (MVMR) to assess the independent effects of urate and BP on eGFR. Effect estimates are presented as standard deviation (SD) change in outcome (95% confidence interval) per SD increase in exposure.

Results

The UVMR analysis showed a bidirectional causal effect between urate and eGFR [urate on log(eGFR): beta=-0.10 (−0.22 to 0.02); log(eGFR) on urate: beta=−0.11 (−0.17 to −0.04)]. We also found bidirectional causal effects between urate and SBP [urate on SBP: beta=0.08 (0.04 to 0.11); SBP on urate: beta=0.13 (0.08 to 0.18)] and urate and DBP [urate on DBP: beta=0.09 (0.05 to 0.14); DBP on urate: beta=0.13 (0.08 to 0.18)]. However, there was weak evidence of a causal effect between BP and eGFR. MVMR results suggested the causal effect of urate on eGFR was independent of BP.

Conclusion

Our results provide evidence for bidirectional causal effects between urate and both eGFR and BP, suggesting urate control as a potential intervention to reduce BP and decline in kidney function in the general population, but little evidence of a causal relationship between BP and eGFR.
Cerebral perivascular spaces as predictors of dementia risk and accelerated brain atrophy
Authors: Barisano Giuseppe , Iv Michael , Choupan Jeiran , Hayden-Gephart Melanie
Published: April 2024

Cerebral small vessel disease, an important risk factor for dementia, lacks robust,in vivomeasurement methods. Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. We developed a novel, robust algorithm to automatically assess PVS count and size on MRI, and investigated their relationship with dementia risk and brain atrophy. We analyzed 46,478 clinical measurements of cognitive functioning and 20,845 brain MRI scans from 10,004 participants (71.1±9.7 years-old, 56.6% women). Fewer PVS and larger PVS diameter at baseline were associated with higher dementia risk and accelerated brain atrophy. Longitudinal trajectories of PVS markers were significantly different in non-demented individuals who converted to dementia compared with non-converters. In simulated placebo-controlled trials for treatments targeting cognitive decline, screening out participants less likely to develop dementia based on our PVS markers enhanced the power of the trial. These novel radiographic cerebrovascular markers may improve risk-stratification of individuals, potentially reducing cost and increasing throughput of clinical trials to combat dementia.
Adenovirus-specific T cells in adults are frequent, cross-reactive to common childhood adenovirus infections and boosted by adenovirus-vectored vaccines
Authors: Mukhopadhyay Rookmini , Lambisia Arnold W. , Hoang Jennifer P. , Ravenhill Benjamin J. , Agoti Charles N. , Krishna Benjamin A.C. , Houldcroft Charlotte J.
Published: April 2024

Human adenoviruses (HAdVs) cause diverse disease presentations as pathogens, and are also used as viral vectors for vaccines and gene therapy products. Preexisting adaptive immune responses to HAdV are known to influence symptom severity, viral clearance and the success of viral vectored products. Of note, approximately 50% of the UK’s adult population has received at least one dose of a chimpanzee adenovirus vectored SARS-CoV-2 vaccine (ChAdOx1) since January 2021.

We used FluoroSpot analysis to quantify the interferon gamma (IFNγ) and interleukin-2 (IL2) responses of healthy blood donors to HAdV species A, B, C, D and F and chimpanzee adenovirus Y25, related to HAdV species E. We find that cellular immune responses to multiple species of human adenovirus are ubiquitous among healthy adult blood donors, and that stimulating PBMC with whole hexon peptide libraries induces a significantly greater IFNγ and IL2 response than using selected peptide pools alone. We then compared the cellular immune responses of ChAdOx1 recipients and control donors using PBMC collected in 2021, and found that homotypic and heterotypic IFNγ responses were significantly boosted in ChAdOx1 recipients but not controls. Finally, we show that in PBMC derived from blood donors, IFNγ responses are made to both conserved and variable regions of the hexon protein.

Future vaccination campaigns using adenoviral vectored vaccines will need to account for the pre-existing exposure of recipients to both circulating HAdVs and vaccines such as ChAdOx1, which convey polyfunctional antiviral T cell responses to even low seroprevalence HAdV types.
Modelling to support decisions about the geographic and demographic extensions of seasonal malaria chemoprevention in Benin
Authors: Lemant Jeanne , Champagne Clara , Houndjo William , Aïssan Julien , Aïkpon Rock , Houetohossou Camille , Kpanou Sakariahou , Goers Roland , Affoukou Cyriaque , Pothin Emilie
Published: April 2024

Background

Seasonal malaria chemoprevention (SMC) has been implemented yearly in northern Benin since 2019 to reduce the malaria burden in children under 5 years of age. Its geographic scope was progressively extended until in 2022 two different extensions of SMC were considered: either demographic - children aged 5 to 10 in the currently targeted departments would also receive SMC, or geographic to children under 5 in new eligible departments to the south. As SMC had neither been implemented in the areas nor age groups suggested for expansion, modelling was used to compare the likely impact of both extensions.

Methods

The model OpenMalaria was calibrated to represent the history of malaria interventions and transmission risk in Benin. Currently planned future interventions and two scenarios for SMC extensions were simulated to inform where impact would be the highest.

Results

The model predicted that between 2024 and 2026 the geographic extension of SMC would avert at least four times more severe malaria cases and five times more direct malaria deaths per targeted child than the demographic extension. However, numbers of severe cases averted per targeted child were similar between health zones eligible for geographic extension.

Conclusions

The geographic extension is more impactful and likely more cost-effective than the demographic extension, and will be implemented from 2024. Health zones were prioritised by availability of community health workers to deliver SMC. Mathematical modelling was a supportive tool to understand the relative impact of the different proposed SMC extensions and contributed to the decision-making process. Its integration significantly enhanced the utilisation of data for decision-making purposes. Rather than being used for forecasting, the model provided qualitative guidance that complemented other types of evidence.
The impact of telemedicine on pediatric hospital capacity and resources: A study protocol for a systematic review
Authors: Wagenaar JHL , Taal HR , Reiss IKM , Kleinsmann MS , Fang JL , Hinrichs S
Published: April 2024

Background

Telemedicine has evolved significantly, demonstrating benefits across various medical fields, including pediatrics. Hospital capacity issues and long distances to reach specialty care are common incentives to use telemedicine. However, current telemedicine research focuses primarily on its effect on clinical outcomes (efficacy) and implementation barriers, leaving capacity outcomes and effectiveness of telemedicine underexplored. This systematic review aims to fill this gap by providing an overview of telemedicine’s impact on pediatric hospital capacity.

Methods

The PRISMA guidelines will be followed. A systematic literature search through the Pubmed, Embase, Cochrane and Web of Science databases will be conducted. Empirical and modelling studies that evaluate the impact of telemedicine on capacity outcomes in a pediatric, neonatal or perinatal population and hospital setting will be included. Two independent researchers will perform screening, data extraction and quality assessment with the mixed methods appraisal tool. Data will be synthetized qualitatively. The primary outcome will be the impact of telemedicine on capacity outcome measures (following WHO definitions) according to each telemedicine type.
Causality between Diabetes and MN: Mendelian randomization and meta-analysis
Authors: Su Zhihang , Luo Ziqi , Wu Di , Liu Wen , Li Wangyang , Yin Zheng , Xue Rui , Wu Liling , Cheng Yuan , Wan Qijun
Published: April 2024

Background

Membranous nephropathy (MN) has not yet been fully elucidated regarding its relationship with Type I and II Diabetes. This study aims to evaluate the causal effect of multiple types of diabetes and MN by summarizing the evidence from the Mendelian randomization (MR) study.

Methods

The statistical data for MN was obtained from a GWAS study encompassing 7,979 individuals. Regarding diabetes, fasting glucose, fasting insulin, and HbA1C data, we accessed the UK-Biobank, within family GWAS consortium, MAGIC, Finnish database, MRC-IEU, and Neale Lab, which provided sample sizes ranging from 17,724 to 298,957. As a primary method in this MR analysis, we employed the Inverse Variance Weighted (IVW), Weighted Median, Weighted mode, MR-Egger, Mendelian randomization pleiotropy residual sum, and outlier (MR-PRESSO) and Leave-one-out sensitivity test. Reverse MR analysis was utilized to investigate whether MN affects Diabetes. Meta-analysis was applied to combine study-specific estimates.

Results

It has been determined that type 2 diabetes, gestational diabetes, type 1 diabetes with or without complications, maternal diabetes, and insulin use pose a risk to MN. Based on the genetic prediction, fasting insulin, fasting blood glucose, and HbA1c levels were not associated with the risk of MN. No heterogeneity, horizontal pleiotropy, or reverse causal relationships were found. The meta-analysis results further validated the accuracy.

Conclusions

The MR analysis revealed the association between MN and various subtypes of diabetes. This study has provided a deeper understanding of the pathogenic mechanisms connecting MN and diabetes.
Cooking fuel and symptoms of chronic respiratory disease in ageing adults: Evidence from West Africa and North America
Authors: Dusing Gabriel , Agbe Eyram Adzo , Quansah Reginald , Boateng Godfred O.
Published: April 2024

Background

The combustion of solid fuels (e.g., wood, coal, and charcoal) for cooking fuel is widespread in low– and middle-income countries. The use of these fuels increases exposure to airborne pollutants which have been shown to increase the risk of disease and premature death, particularly among older individuals. Despite this, most studies examining this association come from India and China. Furthermore, few studies have examined this association among the elderly. This study aims to fill this gap by examining the association between household cooking fuel and chronic respiratory disease.

Methods

We analyzed data from Wave 2 of the World Health Organization’s Study on Global Ageing and Adult Health. Our study sample consists of 7,253 adults aged 50+ from Mexico and Ghana. Logistic regression was conducted to study the association between chronic respiratory disease (measured by whether the participant reported having either (1) a medical diagnosis for chronic obstructive pulmonary disorder, chronic bronchitis, or emphysema, or (2) symptoms suggesting chronic lung infection), and the main cooking fuel used by the household.

Results

The prevalence of chronic respiratory disease was 6.55% and 17.45% for Ghana and Mexico, respectively. 15.96%, and 22.47% of participants lived in households using solid fuels for cooking. Adjusting for covariates, solid fuel use was associated with 1.72 (95%CI: 1.07-2.79; p=0.026) times higher odds of chronic respiratory disease. Regional disparities were found, with individuals in Mexico and Ghana respectively having 1.70 (95%CI:1.01-2.89; p=0.049) and 3.40 (95%CI:1.50-7.72; p=0.004) higher adjusted odds for chronic respiratory disease.

Conclusions

Our results confirm the association found between the use of solid fuels and increased chronic respiratory disease risk. These findings demonstrate the salience of improving access to clean cooking fuels and methods, especially for households in the sub-Saharan region, particularly, women. Policy interventions need to capture the unique needs of women to ensure that health outcomes from energy use are well-mitigated.
Evolving Patterns of COVID-19 Mortality in US Counties: A Longitudinal Study of Healthcare, Socioeconomic, and Vaccination Associations
Authors: Ganjkhanloo Fardin , Ahmadi Farzin , Dong Ensheng , Parker Felix , Gardner Lauren , Ghobadi Kimia
Published: April 2024

The COVID-19 pandemic emphasized the need for pandemic preparedness strategies to mitigate its impacts, particularly in the United States, which experienced multiple waves with varying policies, population response, and vaccination effects. This study explores the relationships between county-level factors and COVID-19 mortality outcomes in the U.S. from 2020 to 2023, focusing on disparities in healthcare access, vaccination coverage, and socioeconomic characteristics.

We conduct multi-variable rolling regression analyses to reveal associations between various factors and COVID-19 mortality outcomes, defined as Case Fatality Rate (CFR) and Overall Mortality to Hospitalization Rate (OMHR), at the U.S. county level. Each analysis examines the association between mortality outcomes and one of the three hierarchical levels of the Social Vulnerability Index (SVI), along with other factors such as access to hospital beds, vaccination coverage, and demographic characteristics.

Our results reveal persistent and dynamic correlations between various factors and COVID-19 mortality measures. Access to hospital beds and higher vaccination coverage showed persistent protective effects, while higher Social Vulnerability Index was associated with worse outcomes persistently. Socioeconomic status and vulnerable household characteristics within the SVI consistently associated with elevated mortality. Poverty, lower education, unemployment, housing cost burden, single-parent households, and disability population showed significant associations with Case Fatality Rates during different stages of the pandemic. Vulnerable age groups demonstrated varying associations with mortality measures, with worse outcomes predominantly during the Original strain. Rural-Urban Continuum Code exhibited predominantly positive associations with CFR and OMHR, while it starts with a positive OMHR association during the Original strain.

This study reveals longitudinal persistent and dynamic factors associated with two mortality rate measures throughout the pandemic, disproportionately affecting marginalized communities. The findings emphasize the urgency of implementing targeted policies and interventions to address disparities in the fight against future pandemics and the pursuit of improved public health outcomes.
Engineering a cell-free biosensor signal amplification circuit with polymerase strand recycling
Authors: Li Yueyi , Lucci Tyler , Dujovne Matias Villarruel , Jung Jaeyoung Kirsten , Capdevila Daiana A , Lucks Julius B
Published: April 2024

Cell-free systems are powerful synthetic biology technologies because of their ability to recapitulate sensing and gene expression without the complications of living cells. Cell-free systems can perform even more advanced functions when genetic circuits are incorporated as information processing components. Here we expand cell-free biosensing by engineering a highly specific isothermal signal amplification circuit called polymerase strand recycling (PSR) that leverages T7 RNA polymerase off-target transcription to recycle nucleic acid inputs within DNA strand displacement circuits. We develop design rules for PSR circuit components and use these rules to construct modular biosensors that can directly sense different RNA targets with limits of detection in the nM range and high specificity. We then use PSR for signal amplification within allosteric transcription factor-based biosensors for small molecule detection. We use a double equilibrium model of transcription factor:DNA and transcription factor:ligand binding interactions to predict biosensor sensitivity enhancement by PSR, and then demonstrate this approach experimentally by achieving 3.6-4.6-fold decreases in biosensor EC50 to sub micromolar ranges. We believe this work expands the current capabilities of cell-free circuits by incorporating PSR, which we anticipate will have a wide range of uses within biotechnology.
Deep Lineage: Single-Cell Lineage Tracing and Fate Inference Using Deep Learning
Authors: Sadria Mehrshad , Zhang Allen , Bader Gary D.
Published: April 2024

Recent advances in single-cell RNA-sequencing and lineage tracing techniques have provided valuable insights into the temporal changes in gene expression during development, tumour progression, and disease onset. However, there are few computational methods available to analyze this information to help understand multicellular dynamics. We introduce Deep Lineage, a novel deep-learning method for analyzing time-series single-cell RNA-sequencing with matched lineage-tracing data. Our method accurately predicts early cell fate biases and gene expression profiles at different time points within a clone, surpassing current state-of-the-art methods in fate prediction accuracy. Additionally, through in silico perturbations in cellular reprogramming and hematopoiesis development data, we show that Deep Lineage can accurately model dynamic multicellular responses while identifying key genes and pathways associated with cell fate determination.
Adaptive loss of tRNA gene expression leads to phage resistance in a marineSynechococcuscyanobacterium
Authors: Zborowsky Sophia , Tahan Ran , Lindell Debbie
Published: April 2024

Synechococcusis a significant primary producer in the oceans, coexisting with cyanophages which are important agents of mortality. Bacterial resistance against phage infection is a topic of significant interest, yet little is known for ecologically relevant systems. Here we use exogenous gene expression and gene disruption to investigate mechanisms underlying intracellular resistance of marineSynechococcus WH5701 to the Syn9 cyanophage. Despite possessing restriction-modification and Gabija defense systems, neither contributed to resistance. Instead, resistance was primarily driven by insufficient levels of LeuTAAtRNA, preventing translation of key phage genes in a passive, intracellular mode of resistance. Restoring cellular tRNA expression rendered the cyanobacterium sensitive to infection. We propose an evolutionary scenario whereby changes in cell codon usage, acquisition of tRNAs by the phage and loss of cell and phage tRNA expression resulted in an effective means of resistance, highlighting the dynamic interplay between bacteria and phages in shaping their co-evolutionary trajectories.
ATM and 53BP1 regulate alternative end joining-mediated V(D)J recombination
Authors: Wang Jinglong , Sadeghi Cheyenne A. , Le Long V. , Le Bouteiller Marie , Frock Richard L.
Published: April 2024

G0/G1-phase alternative end joining (A-EJ) is a recently defined mutagenic pathway characterized by resected deletion and translocation joints that are predominantly direct and are distinguished from A-EJ in cycling cells which rely much more on microhomology-mediated end joining (MMEJ). Using chemical and genetic approaches, we systematically evaluate potential A-EJ factors and DNA damage response (DDR) genes to support this mechanism by mapping the repair fates of RAG1/2-initiated DSBs in the context of Igκ locus V-J recombination and chromosome translocation. Our findings highlight a polymerase theta-independent Parp1-XRCC1/Lig3 axis as central A-EJ components, supported by 53BP1 in the context of an ATM-activated DDR. Mechanistically, we demonstrate varied changes in short-range resection, MMEJ, and translocation, imposed by compromising specific DDR activities, which include polymerase alpha, ATR, DNA2, and Mre11. This study advances our understanding of DNA damage repair within the 53BP1 regulatory domain and the RAG1/2 post-cleavage complex.
T2R14 mediated antimicrobial responses through interactions with CFTR
Authors: Gupte Tejas , Singh Nisha , Bhatia Vikram , Arora Kavisha , Amiri Shayan , Fernhyhough Paul , Naren Anjaparavanda P , Dakshinamurti Shyamala , Chelikani Prashen
Published: April 2024

Bitter taste receptors (T2Rs), are a subset of G protein-coupled receptors (GPCRs) that play a key role in responding to microbial presence at epithelial surfaces. In epithelia, the activities of ion channels and transporters, and of T2Rs, mutually affect each other. The normal function of one such anion channel, cystic fibrosis transmembrane conductance regulator (CFTR), is essential for the maintenance of healthy epithelia, not just in the respiratory but in the digestive and reproductive system as well. Based on evidence that T2R14 activity is affected upon mutations inCFTR, we explored the possibility that T2R14 and CFTR directly interact in cell membranes. The biophysical interaction between these proteins was mapped to specific regions of the CFTR, and was dependent on agonist stimulation of T2R14. Further, T2R14 was found to couple to Gαq, in addition to the canonical Gαi, in response to bacterial and fungal quorum sensing molecules. Whether the interaction with CFTR affects T2R14 driven responses to microbial signals is under investigation.
Notch dimerization contributes to maintenance of intestinal homeostasis by a mechanism involving HDAC2
Authors: Dai Quanhui , Preusse Kristina , Yu Danni , Kovall Rhett A. , Thorner Konrad , Lin Xinhua , Kopan Raphael
Published: April 2024

A tri-protein complex containing NICD, RBPj and MAML1 binds DNA as monomer or, cooperatively, as dimers to regulate transcription. Mice expressing Notchdimerization-deficient (DD) alleles ofNotch1 andNotch2 (NDD) are sensitized to environmental insults but otherwise develop and age normally. Transcriptomic analysis of colonic spheroids uncovered no evidence of dimer-dependent target gene miss-regulation, confirmed impaired stem cell maintenance in-vitro, and discovered an elevated signature of epithelial innate immune response to symbionts, the likely underlying cause for heightened sensitivity in NDD mice. TurboID followed by quantitative nano-spray MS/MS mass-spectrometry analyses in a human colon carcinoma cell line expressing either NOTCH2DDor NOTCH2 revealed an unbalanced interactome, with reduced interaction of NOTCH2DDwith the transcription machinery but relatively preserved interaction with the HDAC2 interactome suggesting modulation via cooperativity. To ask if HDAC2 activity contributes to Notch loss-of-function phenotypes, we used the HDAC2 inhibitor Valproic acid (VPA) and discovered it could prevent the intestinal consequences of gamma secretase inhibitor (DBZ or DAPT) treatment in mice and spheroids, suggesting synergy between HDAC activity and pro-differentiation program in intestinal stem cells.
Polarized
J/ψ
production in semi-inclusive DIS at large
Q2
: Comparing quark fragmentation and photon-gluon fusion
Authors: Copeland Marston , Fleming Sean , Gupta Rohit , Hodges Reed , Mehen Thomas
Published: April 2024

We compare the relative importance of different mechanisms for polarized J/ψ production in semi-inclusive deep inelastic scattering processes at large Q2. The transverse momentum dependent (TMD) factorization framework and nonrelativistic quantum chromodynamics are used to study the leading contributions from light quark fragmentation to polarized J/ψ, and compared to direct production via photon-gluon fusion, which can proceed through color-singlet as well as color-octet mechanisms. We identify kinematic regimes where light quark fragmentation dominates, allowing for the extraction of the S31[8] matrix element, as well as regimes where photon gluon fusion dominates, suggesting that the gluon TMD parton distribution function can be probed.

Published by the American Physical Society
2024
Direct detections of the axionlike particle revisited
Authors: Chao Wei , Feng Jing-Jing , Jin Mingjie
Published: April 2024

Axionlike particles (ALPs) are promising dark matter candidates. Their signals in direct detection experiments arise from the well-known inverse Primakoff effect or the inverse Compton scattering of ALPs with the electron. In this paper, we revisit the direct detection of ALP by carefully considering the interference between the inverse Primakoff amplitude and the inverse Compton amplitude in the scattering process a+e→e+γ for the first time. It shows that the contribution of the interference term turns to be dominated in the scattering for a large ALP energy. Given the new analytical formula, signals or constraints of ALP couplings in various projected experiments are investigated. Our results show that these experiments may put strong constraints on ALP couplings for relatively heavy ALP. We further study projected constraints on ALP from the JUNO experiment, which shows competitive constraints on ALP couplings using a ten-year exposure.

Published by the American Physical Society
2024
Water, Not Salt, Causes Most of the Seebeck Effect of Nonisothermal Aqueous Electrolytes
Authors: Nickel Ole , Ahrens-Iwers Ludwig J. V. , Meißner Robert H. , Janssen Mathijs
Published: April 2024

A temperature difference between two electrolyte-immersed electrodes often yields a voltage Δψ between them. This electrolyte Seebeck effect is usually explained by cations and anions flowing differently in thermal gradients. However, using molecular simulations, we found almost the same Δψ for cells filled with pure water as with aqueous alkali halides. Water layering and orientation near polarizable electrodes cause a large temperature-dependent potential drop χ there. The difference in χ of hot and cold electrodes captures most of the thermovoltage, Δψ≈χhot−χcold.

Published by the American Physical Society
2024
Redetermination of germacrone type II based on single-crystal X-ray data
Authors: Meurer Florian , Bodensteiner Michael , Kolev Iliyan
Published: April 2024

The extraction and purification procedures, crystallization and crystal structure refinement (single-crystal X-ray data) of germacrone type II, C15H22O, are presented. The structural results are compared with a previous powder X-ray synchrotron study [Kaduk et al. (2022). Powder Diffr.
37, 98–104], revealing significant improvements in terms of accuracy and precision. Hirshfeld atom refinement (HAR), as well as Hirshfeld surface analysis, give insight into the intermolecular interactions of germacrone type II.
4-(1H-2,3-Dihydronaphtho[1,8-de][1,3,2]diazaborinin-2-yl)-1-ethylpyridin-1-ium iodide monohydrate
Authors: Hashimoto Shu , Miki Shintaro , Okuno Tsunehisa
Published: April 2024

The cation of the title hydrated salt, C17H17BN3
+·I−·H2O, is a diazaborinane featuring substitution at the 1, 2, and 3 positions in the nitrogen–boron six-membered heterocycle. The cation is approximately planar with a dihedral angle between the pyridyl ring and the diazaborinane ring system of 5.40 (5)°. In the crystal, the cations stack along [100] in an alternating head-to-tail manner, while the iodide ion and water molecule form one-dimensional hydrogen-bonded chains beside the cation stack. The cation stacks and I−–water chains are crosslinked by N—H...I and N—H...O hydrogen bonds.
Preparation, anticorrosion and antifouling behavior of halloysite-loaded nanocomposite with CAP and BTA
Authors: Diao Yaqi , Wang Jihui , Song Renhong , Fei Xue , Xue Zhichang , Hu Wenbin
Published: April 2024

Purpose

The purpose of this paper is to prepare a multifunctional nanocomposite that is slow-release and resistant to seawater corrosion and biofouling corrosion and to explore the synergistic effect between the two corrosion inhibitors.

Design/methodology/approach

The morphology, structure and release properties of CAP@HNTs, BTA@HNTs and CAP/BTA@HNTs were investigated by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, specific surface area analysis and UV spectrophotometry. The corrosion resistance and antimicrobial properties were investigated by electrochemical measurements and bioinhibition rate tests, and the synergistic effect between the two corrosion inhibitors was explored by X-ray photoelectron spectroscopy.

Findings

The CAP/BTA@HNTs are responsive to acidic environments and have significantly improved antibacterial and corrosion resistance compared with CAP@HNTs and BTA@HNTs. CAP and BTA have a positive synergistic effect on anticorrosion and antifouling.

Originality/value

Two types of inhibitors, anticorrosion and antifouling, were loaded into the same nanocontainer to prepare a slow-releasable and multifunctional nanocomposite with higher resistance to seawater corrosion and biocorrosion and to explore the synergistic effect of CAP and BTA on corrosion resistance.
Directors with supply chain experience as heterogeneous network pipes: how does it affect M&A efficiency
Authors: Pei Xudong , Song Juan
Published: April 2024

Purpose

The link between interlocking directors and mergers and acquisitions (M&A) efficiency has been analyzed in an information asymmetry environment. Despite an abundance of evidence highlighting that interlocking directors do contribute to M&A efficiency in an acquirer-target binary relationship, the target is embedded in a complex network of supplier-customer relationships, which implies that the acquirer needs to consider the value of suppliers, distributors and retailers in the target’s supply chain in improving M&A efficiency. Through the lenses of acquirer-target multivariate relationships, this paper aims to examine how directors with supply chain experience (DSCs) act as heterogeneous network pipes to affect M&A efficiency.

Design/methodology/approach

Using a sample of 311 A-share listed firms on the Shanghai and Shenzhen stock exchanges in China during 2011–2020, this paper investigates the relationship between DSCs and M&A efficiency by using ordinary least squares (OLS) regression.

Findings

Through empirical research, we verify a negative relationship between DSCs and M&A duration and an inverted U-shaped relationship between both DSCs and M&A performance, revealing the complexity of the relationship between experience and efficiency. Furthermore, drawing on upper echelon theory, the information value of DSCs will be greatly reduced when executives have overconfident psychological characteristics, which are mainly shown to negatively moderate the relationship between DSCs and M&A performance. We also conduct multiple robustness tests and supplemental analyses to illustrate the robustness and boundaries of our findings. Finally, DSCs are likely more important in environments among growth and mature firms as well as high-growth industries.

Originality/value

We break through the assumption that interlocking directors contribute to M&A efficiency in an acquirer-target binary relationship and examine the impact of DSCs on M&A efficiency based on micro-empirical evidence from the value of target-related upstream or downstream industries, which extends the connotation of interlocking directors and enriches the study related to factors influencing M&A efficiency.
Benchmarking nutrition facts panel label – a consumer ethics perspective using health belief model
Authors: Priya K.M. , Alur Sivakumar
Published: April 2024

Purpose

This study examines how health-conscious consumers utilize nutrition facts panel labels when purchasing food products, focusing specifically on the dimension of ethical evaluation. It aims to understand how ethical considerations influence the decision-making process of consumers who prioritize health. By analyzing the impact of ethical evaluation on label usage, the study sheds light on the significance of ethics in consumer behavior in the context of purchasing packaged edible oil.

Design/methodology/approach

Empirical data were collected using an online survey and a non-ordered questionnaire. In total, 469 valid responses were obtained. The study used SPSS version 27.0 and SmartPLS version 3 for demographic analysis and structural equation modeling.

Findings

The findings suggest that three factors – perceived benefits, perceived threats, and nutrition self-efficacy, positively impact the use of NFP labels. However, perceived barriers negatively influence the use of NFP labels. In additionally, ethical evaluation mediates the usage of NFP labels.

Practical implications

In the health belief model, ethical evaluation functions as a mediator and has a greater influence on NFP label use. This study provides a framework for marketers to promote consumer health consciousness by encouraging them to incorporate NFP labels.

Originality/value

This study is one of the first attempts to demonstrate that ethical evaluation mediate health beliefs and the use of nutrition labels.
Nurturing doctoral excellence: effective strategies for research support services in public university libraries of Kenya
Authors: Sawe Emily , Mwai Naomi , Oyieke Lilian
Published: April 2024

Purpose

The purpose of this study is to examine approaches used by university libraries to enhance the visibility and utilization of research support services (RSSs) among doctoral students and to assess the competencies of library staff in delivering research support services.

Design/methodology/approach

This study used qualitative design approach, purposively sampled 40 librarians (8 university librarians and 32 librarians) in charge of RSSs and use of structured interview.

Findings

The findings of this study revealed three major themes: offline and online strategies, the need for upskilling and professional development programs and proactive empowerment.

Research limitations/implications

This study focused on research support services in chartered public universities in Kenya; private universities were not included.

Practical implications

The need to enhance library staff's ongoing professional development programs, increasing funding to university libraries and proactivity by the libraries to improve the provision and promotion of RSSs to doctoral students in Kenya.

Originality/value

There are limited existing literature in the Kenyan context. This study will fill a knowledge gap and contribute to the literature on academic libraries support and doctoral students experience in Kenyan context.
The promise and perils of coworking in residential areas: a systematic review of health and community impacts
Authors: Vogl Thomas , Orel Marko
Published: April 2024

Purpose

This study aims to explore the manifold implications – health, environmental and economic – of integrating coworking spaces (CSs) into residential settings. The research emphasizes the health-related potential and connected benefits of situating these contemporary spaces of work in retrofitted buildings.

Design/methodology/approach

The research highlights the potential of retrofitted buildings – owing to their urban locations, existing infrastructure, and available space – to accommodate CSs. Employing the preferred reporting items for systematic reviews and meta-analyses (PRISMA) methodology, the paper systematically reviews literature from 2010 to 2021. It investigates the influence of residential CSs on health, community cohesion and environmental sustainability.

Findings

The results indicate that integrating CSs within residential areas can significantly enhance user wellbeing, create a healthier residential environment and positively impact the broader community. Retrofitted buildings emerge as optimal venues for CSs due to their urban positioning and potential to contribute to users' physical, mental and social health. However, the strategic (re)use of retrofitted buildings is crucial, alongside planning to address potential downsides like gentrification.

Research limitations/implications

The study is based on a literature review and may not fully capture the specificities of certain regional or local conditions that could affect the health benefits associated with CSs. In addition to that, the study primarily references European-centric research between 2010 and 2021, indicating a need for more diverse geographic and cultural studies. Further empirical studies are needed to validate the findings behind the following study.

Practical implications

The findings of this study can guide urban planners, policymakers and architects in assessing the feasibility of converting residential buildings into CSs and planning relevant activities. They can leverage the potential health benefits to promote CSs and encourage healthier lifestyle practices in residential communities.

Social implications

Introducing CSs in residential areas can lead to reduced commuting stress, opportunities for physical activities and social interactions, and healthier lifestyle practices. These benefits can enhance the overall well-being of individuals and communities, fostering a stronger social fabric in urban settings.

Originality/value

This research is novel in examining the health benefits associated with CSs in residential areas and the role of retrofitted buildings in promoting such advantages.
The benefits of using a Shared Lives type community response to support survivors of domestic abuse with disabilities and older survivors
Authors: Warburton-Wynn Amanda
Published: April 2024

Purpose

This paper aims to introduce the concept of using the well-established Shared Lives approach to support survivors of domestic abuse with complex needs including those with learning and physical disabilities, older people and carers.

Design/methodology/approach

Survivors with complex needs are often excluded from traditional domestic abuse support services thus increasing their risk and making recovery impossible. Using the Shared Lives approach in suitable cases could address gaps in provision and improve the outcomes for survivors with disabilities, older survivors and carers.

Findings

The paper draws on evidence from reports and research about the experiences of these cohorts of survivors to explain how the Shared Lives approach could increase support options for specific categories of survivors.

Practical implications

Using the Shared Lives approach to support cohorts of victims/survivors who experience barriers to accessing support could improve outcomes for these people, reduce risk of serious harm and improve quality of life.

Originality/value

With the recent recommendation from Association of Directors of Adult Social Services around increasing use of Shared Lives, this paper provides one potential way to meet this recommendation.