bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between the geriatric nutritional risk index and clinical outcomes among peritoneal dialysis patients: A meta-analysis
Authors: Wang Renjie , Liang Yuxiang , Jiang Jiaojiao
Published: May 2024

Background:

To identify the relationship between the geriatric nutritional risk index (GNRI) and clinical outcomes in patients receiving peritoneal dialysis (PD).

Methods:

The PubMed, EBASE, Web of Science and CNKI databases were searched for available studies up to December 25, 2023. The primary outcome was all-cause mortality, and the secondary outcomes included the incidence of PD dropout, major adverse cardiac and cerebrovascular events (MACCEs), technique failure and peritonitis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were combined to evaluate the predictive value of the GNRI for the occurrence of the above endpoints.

Results:

Ten cohort studies with 3897 patients were included. The pooled results demonstrated that a lower GNRI was significantly associated with a greater incidence of all-cause mortality (HR = 0.71, 95% CI: 0.55–0.91; P = .007). In addition, a decreased GNRI predicted the occurrence of dropout from PD (HR = 0.971, 95% CI: 0.945–0.998, P = .034) and MACCE (HR = 0.95, 95% CI: 0.92–0.98, P = .001). However, no significant associations of the GNRI with technique failure (P = .167) or peritonitis (P = .96) were observed.

Conclusion:

A low GNRI is significantly associated with poor clinical outcomes and might serve as a novel and valuable prognostic indicator among PD patients.
Association of immune cells and the risk of esophageal cancer: A Mendelian randomization study in a East Asian population
Authors: Guo Jinzhou , Si Gao , Si Fuchun
Published: May 2024

Immunotherapy has been used in esophageal cancer (EC), but the causal relationship between EC and immune cells is not clear. Although the cellular phenotype has been reported as a biomarker for immunotherapy, the biomarker studies for immunotherapy in EC still face great challenges. Comprehensive 2-sample Mendelian randomization (MR) analysis was performed to determine the causal association between immune cell signatures and EC in this study. Based on publicly available genetic data, we explored causal associations between 731 immune cell signatures and EC risk. EC had no statistically significant effect on immunophenotypes. Nine immunophenotype types were positively associated with the risk of EC: CD20−%B cell, CD20% lymphocytes, CD25 on IgD− CD27−, CD25 on IgD+ CD24+, CD27 on IgD+ CD24+, CD28+ CD45RA− CD8br AC, CD3 on TD CD8br, IgD-CD38dim%B cells, and Mo MDSC AC. In addition, a total of 15 immunophenotypes were identified as causally associated with EC. IgD+ CD38− %B cell, IgD− CD24− %lymphocyte, CD19 on IgD− CD38dim, CD20 on IgD+ CD24+, CD62L-myeloid DC AC, CD4+ AC, Lymphocyte %leukocyte, CD3 on HLA-DR+ T cell, CD3 on CD45RA− CD4+, HVEM on naive CD4+ AC, HVEM on CD45RA− CD4+, CD4 on TD CD4+, CD4 on CD4 Treg, and CD4 on CD39+ resting Treg, and CD4 on activated & secreting Treg. Our study has demonstrated the close connection between immune cells and EC by genetic means, thus providing guidance for future clinical research.
Rare genetic disorders that impair parathyroid hormone synthesis, secretion, or bioactivity provide insights into the diagnostic utility of different parathyroid hormone assays
Authors: Höppner Jakob , Jüppner Harald
Published: May 2024

Purpose of review

Parathyroid hormone (PTH) is the major peptide hormone regulator of blood calcium homeostasis. Abnormal PTH levels can be observed in patients with various congenital and acquired disorders, including chronic kidney disease (CKD). This review will focus on rare human diseases caused by PTH mutations that have provided insights into the regulation of PTH synthesis and secretion as well as the diagnostic utility of different PTH assays.

Recent findings

Over the past years, numerous diseases affecting calcium and phosphate homeostasis have been defined at the molecular level that are responsible for reduced or increased serum PTH levels. The underlying genetic mutations impair parathyroid gland development, involve the PTH gene itself, or alter function of the calcium-sensing receptor (CaSR) or its downstream signaling partners that contribute to regulation of PTH synthesis or secretion. Mutations in the pre sequence of the mature PTH peptide can, for instance, impair hormone synthesis or intracellular processing, while amino acid substitutions affecting the secreted PTH(1–84) impair PTH receptor (PTH1R) activation, or cause defective cleavage of the pro-sequence and thus secretion of a pro- PTH with much reduced biological activity. Mutations affecting the secreted hormone can alter detection by different PTH assays, thus requiring detailed knowledge of the utilized diagnostic test.

Rare diseases affecting PTH synthesis and secretion have offered helpful insights into parathyroid biology and the diagnostic utility of commonly used PTH assays, which may have implications for the interpretation of PTH measurements in more common disorders such as CKD.
Knowledge, Attitude, and Practice in Preventing Infection Among Patients With Cancer Receiving Chemotherapy
Authors: Suwan Natthawan , Kasatpibal Nongyao , Viseskul Nongkran
Published: May 2024

Background:

Oncology patients receiving chemotherapy are at a high risk for developing infections. Identifying factors that predict infection practices among these patients can help improve the quality of care provided.

Purpose:

The purpose of this study was to evaluate the knowledge, attitudes, and practices related to infection prevention in oncology patients receiving chemotherapy.

Methods:

A cross-sectional study was conducted among 170 patients with cancer.

Results:

The majority of participants had a low to moderate level of knowledge, with high levels of attitude and practice related to infection prevention. Knowledge was a significant predictor of attitude and practice, while attitude was a predictor of infection prevention practices. Knowledge and attitude emerged as mutual predictors, which could explain 23% of the variation in practice toward infection prevention (R
2 = 0.230, P = .00).

Conclusions:

Findings indicated that both knowledge and attitude were powerful predictors of practice toward infection prevention.
Weak Correlation Between Perceived and Measured Intensive Care Unit Nursing Workload
Authors: Wallet Florent , Bonnet Audrey , Thiriaud Vincent , Caillet Anaelle , Piriou Vincent , Vacheron Charles-Hervé , Friggeri Arnaud , Dziadzko Mikhail
Published: May 2024

Background:

Efficient management of nursing workload in the intensive care unit (ICU) is essential for patient safety, care quality, and nurse well-being. Current ICU-specific workload assessment scores lack comprehensive coverage of nursing activities and perceived workload.

Purpose:

The purpose of this study was to assess the correlation between ICU nurses’ perceived workload and the Nine Equivalents of Nursing Manpower Use Score (NEMS).

Methods:

In a 45-bed adult ICU at a tertiary academic hospital, nurses’ perceived shift workload (measured with an 11-point Likert scale) was correlated with the NEMS, calculated manually and electronically.

Results:

The study included 1734 observations. The perceived workload was recorded for 77.6% of observations. A weak positive correlation was found between perceived and objectively measured workload.

Conclusion:

Findings indicate a need to consider the multifaceted nature of nursing activities and individual workload perceptions in the ICU.
Pediatric Clinical Staff Perspectives on Secure Messaging
Authors: Taylor Pearson Katherine E.
Published: May 2024

Background:

Secure messaging (SM) is a communication feature within a patient portal that allows patients and clinical staff to exchange health-related information securely and confidentially.

Purpose:

This study aimed to explore how pediatric clinical staff use SM, identify challenges in its implementation, and suggest quality improvements.

Methods:

A descriptive quantitative study was administered using an online survey in a large health care system. The Task, User, Representation, and Function framework guided the research.

Results:

The survey participants were moderately satisfied with the SM. Opportunities to design this system to be more efficient and maximize patient safety were identified.

Conclusion:

Improving training and workflow can aid in incorporating SM into clinician’s daily routines, focusing on enhancing user satisfaction. Future developments aimed at increasing usage and standardizing message content are crucial for encouraging adoption and ensuring patient safety.
Attachment, Mentalization, Emotion Dysregulation, and Empathy in Eating Disorders
Authors: Gagliardini Giulia , Pandolfi Guia , Colli Antonello
Published: May 2024

Eating disorders (EDs) represent a wide range of clinical symptoms related to food intake, body image, and weight issues, and include anorexia nervosa–restricting type (AN-R), anorexia nervosa–binge-purge type (AN-BP), and bulimia nervosa (BN). The aim was to investigate the characteristics of attachment, mentalization, emotion dysregulation, and empathy in a sample of 102 patients with EDs. A sample of 102 patients and therapists completed a series of measures for the assessment of ED pathology, mentalization, empathy, and emotion dysregulation. Pearson correlations and analysis of variance were used to test the characteristics of the variables among the groups. In relation to attachment and emotion dysregulation, no significant differences were found. In relation to mentalization, significant difference in good mentalization was found in AN-R subtype compared with the BN subtype. In relation to empathy, results showed significantly lower scores in BN subtype on affective empathy compared with the AN-BP subtype, and in AN-R subtype on cognitive empathy. Finally, we used Z-scores for each item ranked by value (higher to lower) to develop different clinical prototypes for each group. Our results point toward the clinical need to address the assessed variables, specifically mentalization, emotion dysregulation, and empathy, in the diagnosis and treatment of EDs.
Geriatric proximal femur fracture updates
Authors: Giordano Vincenzo , Woolley Pierre Marie , Heetveld Martin J. , Smith Carla S. , de Ridder Victor
Published: May 2024

Proximal femur fractures in the aging population present a variety of challenges. Physiologically, patients incurring this fracture are typically frail, with significant medical comorbidities, yet require early surgical treatment to restore mobility to prevent deterioration. Socioeconomically, the occurrence of a fragility fracture may be the beginning of the loss of independence, and the burdens of rehabilitation and support are borne by the individual patient and health care systems.
Streptococcus hohhotensis sp. nov., isolated from the breast milk of a healthy woman
Authors: Li Yu , Han Fei , Wu Yue , Li Weicheng , Ren Dongyan , Su Xin , Zhao Lixia , Menghe Bilige , Liu Wenjun
Published: May 2024

Human breast milk contains lactic acid bacteria (LAB), which have an important influence on the composition of the intestinal microbia of infants. In this study, one strain of an α-hemolytic species of the genus Streptococcus, IMAU99199T, isolated from the breast milk of a healthy nursing mother in Hohhot city PR China, was studied to characterise its taxonomic status using phenotypic and molecular taxonomic methods. The results indicated that it represented a member of the mitis–suis clade, pneumoniae subclade of the genus Streptococcus. It is a Gram-stain-positive, catalase-negative and oxidase-negative bacterium, and the cells are globular, paired or arranged in short chains. The results of a phylogenetic analysis of its 16S rRNA gene and two housekeeping genes (gyrB and rpoB) placed it in the genus Streptococcus. A phylogenetic tree based on 135 single-copy genes sequences indicated that IMAU99199T formed a closely related branch well separated from ‘Streptococcus humanilactis’ IMAU99125, ‘Streptococcus bouchesdurhonensis’ Marseille Q6994, Streptococcus mitis NCTC 12261T, ‘Streptococcus vulneris’ DM3B3, Streptococcus toyakuensis TP1632T, Streptococcus pseudopneumoniae ATCC BAA-960T and Streptococcus pneumoniae NCTC 7465T. IMAU99199T and ‘S. humanilactis’ IMAU99125 had the highest average nucleotide identity (93.7 %) and digital DNA–DNA hybridisation (55.3 %) values, which were below the accepted thresholds for novel species. The DNA G+C content of the draft genome of IMAU99199T was 39.8 %. The main cellular fatty acids components of IMAU99199T were C16 : 0 and C16 : 1ω7. It grew at a temperature range of 25–45 °C (the optimum growth temperature was 37 °C) and a pH range of 5.0–8.0 (the optimum growth pH was 7.0). These data indicate that strain IMAU99199T represents a novel species in the genus Streptococcus, for which the name Streptococcus hohhotensis sp. nov. is proposed. The type strain is IMAU99199T (=GDMCC 1.1874T=KCTC 21155T).
3-Nitropropionic acid induces histological and behavioral alterations in adult zebrafish: role of antioxidants on behavioral dysfunction
Authors: Wiprich Melissa Talita , Vasques Rafaela da Rosa , Zaluski Amanda Bungi , Bertoncello Kanandra Taisa , Altenhofen Stefani , Gusso Darlan , Rodrigues Gabriel , Sachett Adrieli , Piato Ângelo , Maito Fabio Luiz Dal Moro , Vianna Monica Ryff Moreira , Bonan Carla Denise
Published: May 2024

Huntington’s disease (HD) is a neurodegenerative disease marked by progressive motor and non-motor symptoms such as neuropsychiatric disruption and cognitive dysfunction. It has been reported that some pathogenic mechanisms resulting in neuronal cell death in this disease involve neurodegeneration and oxidative stress. 3-Nitropropionic acid (3-NPA), a natural toxin that promotes the irreversible suppression of mitochondrial complex II, has been used to understand the HD pathogenesis. This neurotoxin mimics the biochemical, central neurodegeneration, peripheral and behavioral phenotype alterations observed in HD. Here we investigated 3-NPA (60 mg/kg) effects on histological and oxidative stress parameters on brain and muscular tissues. We also evaluated the effects of three antioxidant compounds on 3-NPA-induced behavioral phenotypes in adult zebrafish. For the evaluation of the antioxidant effects, adult zebrafish were submitted to a single acute intraperitoneal injection of vitamin C, creatine, or melatonin following 3-NPA chronic administration (60 mg/kg). 3-NPA treatment caused neurodegeneration, but did not alter the muscular tissue. 3-NPA neither change thiobarbituric acid reactive substances (TBARS) nor nonprotein thiol levels. Vitamin C and creatine treatments recovered the hypolocomotion induced by 3-NPA. Also, vitamin C and melatonin treatments improved the memory dysfunction caused by 3-NPA. Altogether, our findings showed that the 3-NPA induces neurodegeneration in adult zebrafish, and the vitamin C, creatine, and melatonin are beneficial in managing HD-like behavioral phenotypes. Thus, these antioxidants could be thought as complementary pharmacotherapies for the treatment of late-stage HD symptoms.
Transplantation of exogenous mitochondria mitigates myocardial dysfunction after cardiac arrest
Authors: Wang Zhen , Zhu Jie , Xu Mengda , Ma Xuyuan , Shen Maozheng , Yan Jingyu , Gan Guosheng , Zhou Xiang
Published: May 2024

The incidence of post-cardiac arrest myocardial dysfunction (PAMD) is high, and there is currently no effective treatment available. This study aims to investigate the protective effects of exogenous mitochondrial transplantation. Exogenous mitochondrial transplantation can enhance myocardial function and improve the survival rate. Mechanistic studies suggest that mitochondrial transplantation can limit impairment in mitochondrial morphology, augment the activity of mitochondrial complexes II and IV, and raise ATP level. As well, mitochondrial therapy ameliorated oxidative stress imbalance, reduced myocardial injury, and thus improved PAMD after cardiopulmonary resuscitation (CPR).
Downregulation of PIK3IP1/TrIP on T cells is controlled by TCR signal strength, PKC and metalloprotease-mediated cleavage
Authors: Murter Benjamin M. , Robinson Sean C. , Banerjee Hridesh , Lau Louis , Uche Uzodinma U. , Szymczak-Workman Andrea L. , Kane Lawrence P.
Published: May 2024

The protein known as PI3K-interacting protein (PIK3IP1), or transmembrane inhibitor of PI3K (TrIP), is highly expressed by T cells and can modulate PI3K activity in these cells. Several studies have also revealed that TrIP is rapidly downregulated following T cell activation. However, it is unclear as to how this downregulation is controlled. Using a novel monoclonal antibody that robustly stains cell-surface TrIP, we demonstrate that TrIP is lost from the surface of activated T cells in a manner dependent on the strength of signaling through the T cell receptor (TCR) and specific downstream signaling pathways, in particular classical PKC isoforms. TrIP expression returns by 24 hours after stimulation, suggesting that it may play a role in resetting TCR signaling at later time points. We also provide evidence that ADAM family proteases are required for both constitutive and stimulation-induced downregulation of TrIP in T cells. Finally, by expressing truncated forms of TrIP in cells, we identify the region in the extracellular stalk domain of TrIP that is targeted for proteolytic cleavage.
Divergent gene expression patterns in alcohol and opioid use disorders lead to consistent alterations in functional networks within the Dorsolateral Prefrontal Cortex
Authors: MacDonald Martha , Fonseca Pablo A. S. , Johnson Kory , Murray Erin M , Kember Rachel L , Kranzler Henry , Mayfield Dayne , da Silva Daniel
Published: May 2024

Substance Use Disorders (SUDs) manifest as persistent drug-seeking behavior despite adverse consequences, with Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) representing prevalent forms associated with significant mortality rates and economic burdens. The co-occurrence of AUD and OUD is common, necessitating a deeper comprehension of their intricate interactions. While the causal link between these disorders remains elusive, shared genetic factors are hypothesized. Leveraging public datasets, we employed genomic and transcriptomic analyses to explore conserved and distinct molecular pathways within the dorsolateral prefrontal cortex associated with AUD and OUD. Our findings unveil modest transcriptomic overlap at the gene level between the two disorders but substantial convergence on shared biological pathways. Notably, these pathways predominantly involve inflammatory processes, synaptic plasticity, and key intracellular signaling regulators. Integration of transcriptomic data with the latest genome-wide association studies (GWAS) for problematic alcohol use (PAU) and OUD not only corroborated our transcriptomic findings but also confirmed the limited shared heritability between the disorders. Overall, our study indicates that while alcohol and opioids induce diverse transcriptional alterations at the gene level, they converge on select biological pathways, offering promising avenues for novel therapeutic targets aimed at addressing both disorders simultaneously.
Network pharmacology, single gene survival analysis and molecular docking to study the mechanism of Sotetsuflavone in the treatment of pancreatic cancer
Authors: Chu Zi-Yong , Zi Xue-Jiao
Published: May 2024

Pancreatic cancer is a highly lethal cancer with limited treatment options. The number of pancreatic cancer patients is increasing rapidly worldwide. Many natural products have been shown to have anticancer activity in a range of studies. Sotetsuflavone is derived fromCycas revolutaThunb. and exhibits anticancer activity. The present study incorporates network pharmacology, single gene survival analysis, gene expression analysis and molecular docking to reveal the mechanism of Sotetsuflavone in the treatment of pancreatic cancer. Initially, it was evaluated through multiple databases for a comprehensive pharmacological evaluation of Sotetsuflavone. Then, the target information of Sotetsuflavone and pancreatic cancer was searched and screened using public databases. According to the results of matching the potential targets of Sotetsuflavone with the targets of pancreatic cancer, the protein-protein interaction (PPI) network was constructed by using the STRING database and imported into Cytoscape 3.9.0 for the network analysis to screen the hub targets, and then classify and co-expression analysis was carried out on the hub targets. Then, we conducted Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of potential and hub targets and discovered that these targets were involved in pancreatic cancer-related signalling pathways. In addition, the GEPIA 2 platform was used to be performed for single gene survival analysis and gene expression analysis, and AutoDock Vina was employed for molecular docking analysis. In total, we have acquired 31 hub targets for the treatment of pancreatic cancer by Sotetsuflavone, namely ABCB1, AURKA, CDK1, and so on. Kaplan-Meier survival analyses demonstrated that ABCB1, AURKA, CDK1, HDAC6, MET, and MMP3 are promising hub targets that can be used as biomarkers for pancreatic cancer diagnosis and prognosis. These hub targets are highly expressed in pancreatic cancer tissues compared to normal tissues. The molecular docking results showed a strong binding capacity of Sotetsuflavone to these hub targets. In summary, it is proposed that Sotetsuflavone is a new anticancer drug, which can regulate cancer-related signalling pathways such as pancreatic cancer by inhibiting the activities of ABCB1, AURKA, CDK1, HDAC6, MET, and MMP3, which are hub targets with up-regulated expression in pancreatic cancer tissues, in order to treat pancreatic cancer. However, it also requires a series of in vivo and in vitro studies to ensure its safety and efficacy.
GDF15 knockout does not substantially impact perinatal body weight or neonatal outcomes in mice
Authors: Mulcahy Molly C. , Habbal Noura El , Redd JeAnna R. , Sun Haijing , Gregg Brigid E. , Bridges Dave
Published: May 2024

Growth differentiation factor-15 (GDF15) increases in circulation during pregnancy and has been implicated in food intake, weight loss, complications of pregnancy, and metabolic illness. We used aGdf15knockout mouse model (Gdf15-/-)to assess the role of GDF15 in body weight regulation and food intake during pregnancy. We found thatGdf15-/-dams consumed a similar amount of food and gained comparable weight during the course of pregnancy compared toGdf15+/+dams. Insulin sensitivity on gestational day 16.5 was also similar between genotypes. In the postnatal period, litter size, and survival rates were similar between genotypes. There was a modest reduction in birth weight ofGdf15-/-pups, but this difference was no longer evident postnatal day 3.5 to 14.5. We observed no detectable differences in milk volume production or milk fat percentage. These data suggest that GDF15 is dispensable for changes in food intake, and body weight as well as insulin sensitivity during pregnancy in a mouse model.
Machine learning-inferred and energy landscape-guided analyses reveal kinetic determinants of CRISPR/Cas9 gene editing
Authors: Jin Lei , Liyanage Risi , Duan Dongsheng , Chen Shi-Jie
Published: May 2024

The CRISPR/Cas nucleases system is widely considered the most important tool in genome engineering. However, current methods for predicting on/off-target effects and designing guide RNA (gRNA) rely on purely data-driven approaches or focus solely on the system’s thermal equilibrium properties. Nonetheless, experimental evidence suggests that the process is kinetically controlled rather than being in equilibrium. In this study, we utilized a vast amount of available data and combined random forest, a supervised ensemble learning algorithm, and free energy landscape analysis to investigate the kinetic pathways of R-loop formation in the CRISPR/Cas9 system and the intricate molecular interactions between DNA and the Cas9 RuvC and HNH domains. The study revealed (a) a novel three-state kinetic mechanism, (b) the unfolding of the activation state of the R-loop being the most crucial kinetic determinant and the key predictor for on- and off-target cleavage efficiencies, and (c) the nucleotides from positions +13 to +16 being the kinetically critical nucleotides. The results provide a biophysical rationale for the design of a kinetic strategy for enhancing CRISPR/Cas9 gene editing accuracy and efficiency.
Reinforcing Tunnel Network Exploration in Proteins Using Gaussian Accelerated Molecular Dynamics
Authors: Mandal Nishita , Surpeta Bartlomiej , Brezovsky Jan
Published: May 2024

Tunnels are structural conduits in biomolecules responsible for transporting chemical compounds and solvent molecules to and from the active site. They have been shown to be present in a wide variety of enzymes across all functional and structural classes. However, the study of such pathways is experimentally challenging because they are typically transient. Computational methods such as molecular dynamics (MD) simulations have been successfully proposed to explore tunnels. Conventional MD (cMD) provides structural details to characterize tunnels but suffers from sampling limitations to capture rare tunnel openings on longer timescales. Therefore, in this study, we explored the potential of Gaussian accelerated MD (GaMD) simulations to improve the exploration of complex tunnel networks in enzymes. We used the haloalkane dehalogenase LinB and its two variants with engineered transport pathways, which are not only well-known for their application potential but have also been extensively studied experimentally and computationally regarding their tunnel networks and their importance in multi-step catalytic reactions. Our study demonstrates that GaMD efficiently improves tunnel sampling and allows the identification of all known tunnels for LinB and its two mutants. Furthermore, the improved sampling provided insight into a previously unknown transient side tunnel (ST). The extensive conformational landscape explored by GaMD simulations allowed us to investigate in detail the mechanism of ST opening. We determined variant-specific dynamic properties of ST opening, which were previously inaccessible due to limited sampling of cMD. Our comprehensive analysis supports multiple indicators of the functional relevance of the ST, emphasizing its potential significance beyond structural considerations. In conclusion, our research proves that the GaMD method can overcome the sampling limitations of cMD for the effective study of tunnels in enzymes, providing further means for identifying rare tunnels in enzymes with potential for drug development, precision medicine, and rational protein engineering.
PEX39 facilitates the peroxisomal import of PTS2 proteins
Authors: Chen Walter W. , Rodrigues Tony A. , Wendscheck Daniel , Pedrosa Ana G. , Yang Chendong , Francisco Tânia , Möcklinghoff Till , Zografakis Alexandros , Nunes-Silva Bernardo , Avraham Reut Ester , Silva Ana R. , Ferreira Maria J. , Das Hirak , Bender Julian , Oeljeklaus Silke , Sondhi Varun , Schuldiner Maya , Zalckvar Einat , Hofmann Kay , Waterham Hans R. , DeBerardinis Ralph J. , Azevedo Jorge E. , Warscheid Bettina
Published: May 2024

Peroxisomes are metabolic organelles essential for human health. Defects in peroxisomal biogenesis proteins (peroxins/PEXs) cause devastating disease. PEX7 binds newly synthesized proteins containing a type 2 peroxisomal targeting signal (PTS2) to enable their import from the cytosol into peroxisomes, although many aspects of this import pathway remain enigmatic. Utilizingin vitroassays, yeast, and human cells, we show that PEX39, a previously uncharacterized protein, is a cytosolic peroxin that facilitates PTS2-protein import by binding PEX7 and stabilizing its interaction with PTS2 cargo. PEX39 and PEX13, a peroxisomal membrane translocon protein, both possess a KPWE motif necessary for PEX7 binding. Sequential binding of PEX7 to this motif in PEX39 and PEX13 provides a novel paradigm for how PTS2 cargo engage the translocation machinery. Collectively, our work uncovers an ancient and functionally important relationship among PEX39, PEX7, and PEX13, offering insights that will advance our understanding of peroxisomal biogenesis and disease.
Metabolic immaturity of newborns and breast milk bile acid metabolites are the central determinants of heightened neonatal vulnerability to norovirus diarrhea
Authors: Peiper Amy M. , Aparicio Joyce Morales , Phophi Lufuno , Hu Zhengzheng , Helm Emily W. , Phillips Matthew , Williams Caroline G. , Subramanian Saravanan , Cross Michael , Iyer Neha , Nguyen Quyen , Newsome Rachel , Jobin Christian , Langel Stephanie N. , Bucardo Filemon , Becker-Dreps Sylvia , Tan Xiao-Di , Dawson Paul A. , Karst Stephanie M.
Published: May 2024

Noroviruses are the leading global cause of acute gastroenteritis, responsible for 685 million annual cases. While all age groups are susceptible to noroviruses, children are vulnerable to more severe infections than adults, underscored by 200 million pediatric cases and up to 200,000 deaths in children annually. Understanding the basis for the increased vulnerability of young hosts is critical to developing effective treatments. The pathogenic outcome of any enteric virus infection is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors. A central mediator in these complex relationships are host- and microbiota-derived metabolites. Noroviruses bind a specific class of metabolites, bile acids, which are produced by the host and then modified by commensal bacterial enzymes. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Considering these opposing effects, the microbiota-regulated balance of the bile acid pool may be a key determinant of the pathogenic outcome of a norovirus infection. The bile acid pool in newborns is unique due to immaturity of host metabolic pathways and developing gut microbiota, which could underlie the vulnerability of these hosts to severe norovirus infections. Supporting this concept, we demonstrate herein that microbiota and their bile acid metabolites protect from severe norovirus diarrhea whereas host-derived bile acids promote disease. Remarkably, we also report that maternal bile acid metabolism determines neonatal susceptibility to norovirus diarrhea during breastfeeding by delivering proviral bile acids to the newborn. Finally, directed targeting of maternal and neonatal bile acid metabolism can protect the neonatal host from norovirus disease. Altogether, these data support the conclusion that metabolic immaturity in newborns and ingestion of proviral maternal metabolites in breast milk are the central determinants of heightened neonatal vulnerability to norovirus disease.
Diffusion barriers imposed by tissue topology shape morphogen gradients
Authors: Schlissel Gavin , Meziane Miram , Narducci Domenic , Hansen Anders S. , Li Pulin
Published: May 2024

Animals use a small number of morphogens to pattern tissues, but it is unclear how evolution modulates morphogen signaling range to match tissues of varying sizes. Here, we used single molecule imaging in reconstituted morphogen gradients and in tissue explants to determine that Hedgehog diffused extra-cellularly as a monomer, and rapidly transitioned between membrane-confined and -unconfined states. Unexpectedly, the vertebrate-specific protein SCUBE1 expanded Hedgehog gradients by accelerating the transition rates between states without affecting the relative abundance of molecules in each state. This observation could not be explained under existing models of morphogen diffusion. Instead, we developed a topology-limited diffusion model in which cell-cell gaps create diffusion barriers, and morphogens can only overcome the barrier by passing through a membrane-unconfined state. Under this model, SCUBE1 promotes Hedgehog secretion and diffusion by allowing it to transiently overcome diffusion barriers. This multiscale understanding of morphogen gradient formation unified prior models and discovered novel knobs that nature can use to tune morphogen gradient sizes across tissues and organisms.
Floral Cues and Flower Handling Tactics Affect Switching Decisions by Nectar-Foraging Bumble Bees
Authors: Baek Minjung , Garcia Jonathan S. , Papaj Daniel R.
Published: May 2024

Nectar foraging bees change their use of floral resources as plant species appear in the environment and disappear over their lifetimes. The new flowers used may involve different cues and different nectar extraction tactics. Although bumble bees can adapt to changes in floral cues and required tactics, little is known about whether bees prioritize switching tactics or floral cues when deciding which plant species to switch to. In a laboratory assay, we forcedBombus impatiens(common eastern bumble bee) workers either to switch the handling tactic they were using or to continue using the tactic but to switch the colour of artificial flowers foraged on. We examined whether bees’ tendency to change their tactics was influenced by how similar in colour novel flowers were to familiar ones. We conducted a 2 × 2 factorial experiment using artificial flowers, manipulating the handling tactic that bees were initially trained (legitimate visitation or nectar robbing) and the similarity between novel and trained colours (similar or distinct). We found that under most conditions bees preferred to switch flower colours and retain handling tactics. However, when given experience with legitimate visitation and when novel flowers were markedly different in colour from those they had experienced previously, bees tended to switch tactic while continuing to forage on flowers of the same colour. These findings suggest that the similarity in colour of a new floral resource to the currently exploited resource, along with the flower handling tactic employed by bees, jointly plays an important role in decision-making by foraging bumble bees.
Transient hypoxia followed by progressive reoxygenation is required for efficient skeletal muscle repair through Rev-ERBα modulation
Authors: Quétin Marie , Vartanian Audrey Der , Dubois Christelle , Berthier Juliette , Ledoux Marine , Michineau Stéphanie , Drayton-Libotte Bernadette , Sotiropoulos Athanassia , Relaix Frédéric , Gervais Marianne
Published: May 2024

Muscle stem cells (MuSCs) are essential for skeletal muscle repair. Following injury, MuSCs reside in low oxygen environments until muscle fibers and vascularization are restablished. The dynamics of oxygen levels during the regenerative process and its impact on muscle repair has been underappreciated. We confirm that muscle repair is initiated in a low oxygen environment followed by gradual reoxygenation. Strikingly, when muscle reoxygenation is limited by keeping mice under systemic hypoxia, muscle repair is impaired and leads to the formation of hypotrophic myofibers.In vivo, sustained hypoxia decreases the ability of MuSCs to differentiate and fuse independently of HIF-1α. Prolonged hypoxia specifically affects the circadian clock by increasingRev-erbαexpression in MuSCs. Using pharmacological tools, we demonstrate that Rev-ERBα negatively regulates myogenesis by reducing late myogenic cell fusion under prolonged hypoxia. Our results underscore the critical role of progressive muscle reoxygenation after transient hypoxia in coordinating proper myogenesis through Rev-ERBα.
Hedgehog-dependent and Hedgehog-independent roles for Growth Arrest Specific 1 in mammalian kidney morphogenesis
Authors: Franks Nicole E. , Allen Benjamin L.
Published: May 2024

Growth arrest specific 1 (GAS1) is a key regulator of mammalian embryogenesis, best known for its role in Hedgehog (HH) signaling, but with additional described roles in the FGF, RET, and NOTCH pathways. Previous work indicated a later role for GAS1 in kidney development through FGF pathway modulation. Here, we demonstrate that GAS1 is essential for both mesonephrogenesis and metanephrogenesis– most notably,Gas1deletion in mice results in renal agenesis in a genetic background-dependent fashion. Mechanistically, GAS1 promotes mesonephrogenesis in a HH-dependent fashion, performing a unique co-receptor function, while promoting metanephrogenesis in a HH-independent fashion, acting as a putative secreted RET co-receptor. Our data indicate thatGas1deletion leads to renal agenesis through a transient reduction in metanephric mesenchyme proliferation– a phenotype that can be rescued by exogenous RET pathway stimulation. Overall, this study indicates that GAS1 contributes to early kidney development through the integration of multiple different signaling pathways.
Quantum spin liquid ground state in the trimer rhodate
Ba4NbRh3O12
Authors: Bandyopadhyay Abhisek , Lee S. , Adroja D. T. , Stenning G. B. G. , Berlie Adam , Lees M. R. , Saha R. A. , Takegami D. , Meléndez-Sans A. , Poelchen G. , Yoshimura M. , Tsuei K. D. , Hu Z. , Kao Cheng-Wei , Huang Yu-Cheng , Chan Ting-Shan , Choi Kwang-Yong
Published: May 2024

Frustrated magnets offer a plethora of exotic magnetic ground states, including quantum spin liquids (QSLs), in which enhanced quantum fluctuations prevent a long-range magnetic ordering of the strongly correlated spins down to lowest temperature. Here we have investigated the trimer based mixed valence hexagonal rhodate Ba4NbRh3O12 using a combination of dc and ac magnetization, electrical resistivity, specific heat, and muon spin rotation/relaxation (μSR) measurements. Despite the substantial antiferromagnetic exchange interactions, as evident from the Weiss temperature (θW∼−35 to −45K), among the Rh-local moments, neither long-range magnetic ordering nor spin freezing is observed down to at least 50 mK, in ac-susceptibility, specific heat, and zero-field μSR measurements (down to 0.26 K). We ascribe the absence of any magnetic transition to enhanced quantum fluctuations as a result of geometrical frustration arising out of the edge-sharing equilateral Rh-triangular network in the structure. Our longitudinal-field μSR result evidences persistent spin fluctuations down to 0.26 K, thus stabilizing a dynamic QSL ground state in Ba4NbRh3O12. Furthermore, the magnetic specific heat data at low T reveal a significant T-linear contribution plus a quadratic T dependence, which may indicate the gapless Dirac QSL phenomenology of the spinon excitations with a linear dispersion.

Published by the American Physical Society
2024
Out-of-Equilibrium Fluctuation-Dissipation Bounds
Authors: Tesser Ludovico , Splettstoesser Janine
Published: May 2024

We prove a general inequality between the charge current and its fluctuations valid for any weakly interacting coherent electronic conductor and for any stationary out-of-equilibrium condition, thereby going beyond established fluctuation-dissipation relations. The developed saturates at large temperature bias and reveals additional insight for heat engines, since it limits the output power by power fluctuations. It is valid when the thermodynamic uncertainty relations break down due to quantum effects and provides stronger constraints close to thermovoltage.

Published by the American Physical Society
2024
Does information matter? Online discourse on the Yemenite children’s affair in Israel after release of archival documents
Authors: Peled Roy , Yavetz Gal
Published: May 2024

Purpose

This study evaluates how publicly available archival documents shaped online discussions about allegations that thousands of children were kidnapped during the 1950s in Israel, known as the Yemenite children’s affair. It examines if access to historical records leads to more informed and rational public discourse, especially on social media.

Design/methodology/approach

Using content analysis, this study examines Facebook posts from media outlets, politicians, NGOs and public groups between 2016 and 2021 to understand how the Israeli State Archives’ release of over 300,000 documents affected support of the kidnapping.

Findings

Despite extensive archival information debunking the kidnapping theory, public opinion and discourse largely continued to support it. This suggests a complex interaction between information availability, preexisting beliefs, echo chambers and group allegiances, suggesting that access to factual data alone may not effectively challenge established beliefs in online public settings.

Research limitations/implications

Since data were collected only from Facebook, our conclusions cannot be generalized to other platforms. The study relies only on publicly accessible data and does not establish causality between exposure to information and shifts in opinion. Our findings show that disclosing archival information does not significantly benefit public political discourse on contentious topics but also point to the advantages of mediating information by politicians, NGOs and journalists.

Originality/value

As a unique case study, this research contributes to understanding the role of historical archives in digital-age public discourse. It highlights their potential and limitations in facilitating informed debate and deliberation, emphasizing the complexity of influencing established beliefs with factual data.
The implications of COVID-19 on ESG performance and financial reporting quality in Egypt
Authors: ElHawary Engy , Elbolok Rasha
Published: May 2024

Purpose

This examine the impact of environmental, social and governance (ESG) performance on financial reporting quality (FRQ) before and during COVID-19 in the Egyptian market.

Design/methodology/approach

This study uses quarterly data from 2017 to 2021 to draw conclusions, with a sample consisting of 486 firm-year observations for 27 Egyptian companies listed on the Standard and Poor’s/Egyptian Stock Exchange ESG index. This study uses both firms’ ESG scores and the Beneish Model, an earnings detection model, as proxies for FRQ. COVID-19 effects on ESG performance and FRQ were examined by using Pearson’s correlation coefficient and two-stage least squares.

Findings

COVID-19 has a significant impact on the link between ESG and FRQ. This implies that corporations with high ESG performance are less likely to manipulate earnings (having a low M-score) and thus provide high FRQ during the COVID-19 pandemic. Moreover, there is a significant positive relationship between firm size, leverage and M-Score, indicating that large firms typically present a high FRQ.

Research limitations/implications

The sample size and data availability are the main research limitations. Additionally, this study only considers the effects of firms’ ESG performance on FRQ during the COVID-19 pandemic. Thus, future research should consider other factors associated with investors’ corporate social responsibility (CSR).

Practical implications

This research has practical implications for market regulators seeking to establish a legislative framework and enhance guidance to mandate managers to provide ESG data and CSR reports appropriate for Egypt and other developing economies in times of crisis.

Social implications

Promoting the adoption of ESG practices in business, particularly during crises, has the potential to effectively provide high-quality and reliable financial reporting required for investment.

Originality/value

This study aspires to address notable deficiencies in the pertinent literature concerning the relationship between ESG performance and FRQ during COVID-19. To the best of the authors’ knowledge, little is known about how ESG performance changes in response to pandemics in emerging markets. To address this gap, this study examines the effects of COVID-19 on the relationship between ESG performance and FRQ in Egyptian-listed firms from 2017 to 2021.
Phygital customer journey: a practice-based approach
Authors: Mele Cristina , Di Bernardo Irene , Ranieri Angelo , Russo Spena Tiziana
Published: May 2024

Purpose

The study aims to delve into the “phygital customer journey” (PCJ), which merges physical and digital interactions in customer experiences, using a practice-based lens to reveal the underlying dynamics of these blended encounters.

Design/methodology/approach

Feedback from 60 individuals established the groundwork for a qualitative analysis. They chronicled customer journeys through diaries and used UXPressia software for journey mapping. This strategy enabled a detailed exploration of the PCJ, focusing on customers’ lived experiences and perceptions.

Findings

The study presents an integrative framework for the PCJ, identifying four key elements: hybrid artefacts (the melding of digital and physical tools/interfaces), blended contexts (the seamless integration of digital and physical spaces), circular actions (the non-linear paths of customer engagement) and intertwined emotions (the complex emotional responses to phygital experiences). These elements underscore the intricate and interconnected nature of the PCJ.

Originality/value

This study advances the field by applying a practice-based approach to unravel the complexities of the PCJ, illuminating the nuanced interplay between digital and physical realms. This innovative lens foregrounds the significance of practices in consumer experiences, thereby contributing to a deeper academic and practical understanding of phygital integration.
Thermal plasticity has higher fitness costs among thermally tolerant genotypes of Tigriopus californicus
Authors: Bogan Samuel N. , Porat Olivia I. , Meneses Michael J. , Hofmann Gretchen E.
Published: May 2024

Under climate change, ectotherms will likely face pressure to adapt to novel thermal environments by increasing their upper thermal tolerance and its plasticity, a measure of thermal acclimation. Ectotherm populations with high thermal tolerance are often less thermally plastic, a trade‐off hypothesized to result from (i) a phenotypic limit on thermal tolerance above which plasticity cannot further increase the trait, (ii) negative genetic correlation or (iii) fitness trade‐offs between the two traits. Whether each hypothesis causes negative associations between thermal tolerance and plasticity has implications for the evolution of each trait.

We empirically tested the limit and trade‐off hypotheses by leveraging the experimental tractability and thermal biology of the intertidal copepod Tigriopus californicus. Using populations from four latitudinally distributed sites in coastal California, six lines per population were reared under a laboratory common garden for two generations. Ninety‐six full sibling replicates (n = 4–5 per line) from a third generation were developmentally conditioned to 21.5 and 16.5°C until adulthood. We then measured the upper thermal tolerance and fecundity of sibships at each temperature.

We detected a significant trade‐off in fecundity, a fitness corollary, between baseline thermal tolerance and its plasticity. Tigriopus californicus populations and genotypes with higher thermal tolerance were less thermally plastic. We detected negative directional selection on thermal plasticity under ambient temperature evidenced by reduced fecundity. These fitness costs of plasticity were significantly higher among thermally tolerant genotypes, consistent with the trade‐off hypothesis. This trade‐off was evident under ambient conditions, but not high temperature.

Observed thermal plasticity and fecundity were best explained by a model incorporating both the limit and trade‐off hypotheses rather than models with parameters associated with one hypothesis. Effects of population and family on tolerance and plasticity negatively covaried, suggesting that a negative genetic correlation could not be ruled as contributing to negative associations between the traits. Our study provides a novel empirical test of the fitness trade‐off hypothesis that leverages a strong inference approach. We discuss our results' insights into how thermal adaptation may be constrained by physiological limits, genetic correlations, and fitness trade‐offs between thermal tolerance and its plasticity.

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