bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermotherapy has Sexually Dimorphic Responses in APP/PS1 Mice
Authors: McFadden Samuel A. , Peck Mackenzie R. , Sime Lindsey N. , Cox MaKayla F. , Ikiz Erol D. , Findley Caleigh A. , Quinn Kathleen , Fang Yimin , Bartke Andrzej , Hascup Erin R. , Hascup Kevin N.
Published: March 2024

A thermoregulatory decline occurs with age due to changes in muscle mass, vasoconstriction, and metabolism that lowers core body temperature (Tc). Although lower Tc is a biomarker of successful aging, we have previously shown this worsens cognitive performance in the APP/PS1 mouse model of Alzheimer’s disease (AD) [1]. We hypothesized that elevating Tc with thermotherapy would improve metabolism and cognition in APP/PS1 mice. From 6-12 months of age, male and female APP/PS1 and C57BL/6 mice were chronically housed at 23 or 30°C. At 12 months of age, mice were assayed for insulin sensitivity, glucose tolerance, and spatial cognition. Plasma, hippocampal, and peripheral (adipose, hepatic, and skeletal muscle) samples were procured postmortem and tissue-specific markers of amyloid accumulation, metabolism, and inflammation were assayed. Chronic 30°C exposure increased Tc in all groups except female APP/PS1 mice. All mice receiving thermotherapy had either improved glucose tolerance or insulin sensitivity, but the underlying processes responsible for these effects varied across sexes. In males, glucose regulation was influenced predominantly by hormonal signaling in plasma and skeletal muscle glucose transporter 4 expression, whereas in females, this was modulated at the tissue level. Thermotherapy improved spatial navigation in male C57BL/6 and APP/PS1 mice, with the later attributed to reduced hippocampal soluble amyloid-β (Aβ)42. Female APP/PS1 mice exhibited worse spatial memory recall after chronic thermotherapy. Together, the data highlights the metabolic benefits of passive thermotherapy, but future studies are needed to determine therapeutic benefits for those with AD.
Global invasion history and genomic signatures of adaptation of a highly invasive lace bug
Authors: Du Zhenyong , Wang Xuan , Duan Yuange , Liu Shanlin , Tian Li , Song Fan , Cai Wanzhi , Li Hu
Published: March 2024

Invasive species cause enormous economic and ecological damage. Climate change has resulted in an unprecedented increase in the number and impact of invaders. The mechanisms underlying invasions, however, are largely unclear. The sycamore lace bug,Corythucha ciliata, is a highly invasive species that originated in North America. Its population has expanded over the Northern Hemisphere since the 1960s. In this study, we assemble the lace bug’s genome using high-coverage PacBio, Illumina, and Hi-C sequencing. We identify 15,278 protein-coding genes and expansion of gene families with oxidoreductase and metabolic activities. In-depth resequencing of 402 samples collected from native and nine invasive countries across three continents identified 2.74 million single nucleotide polymorphisms. We resolve two major invasion routes of this lace bug from North America through both Europe and Japan, forming a contact zone in East Asia. Genomic signatures of selection associated with invasion and long-term balancing selection in native ranges are identified. These genomic signatures overlap with each other and the expanded genes, suggesting an improvement in the oxidative stress and thermal tolerance of this species. Our findings offer valuable insights into the genomic architecture and adaptive evolution underlying the invasive capabilities of species in the face of rapid environmental changes.
Simulation of zonation-function relationships in the liver using coupled multiscale models: Application to drug-induced liver injury
Authors: Gerhäusser Steffen , Lambers Lena , Mandl Luis , Franquinet Julian , Ricken Tim , König Matthias
Published: March 2024

Multiscale modeling requires the coupling of models on different scales, often based on different mathematical approaches and developed by different research teams. This poses many challenges, such as defining interfaces for coupling, reproducible exchange of submodels, efficient simulation of the models, or reproducibility of results. Here, we present a multiscale digital twin of the liver that couples a partial differential equation (PDE)-based porous media approach for the hepatic lobule with cellular-scale ordinary differential equation (ODE)-based models. The models based on the theory of porous media describe transport, tissue mechanical properties, and deformations at the lobular scale, while the cellular models describe hepatic metabolism in terms of drug metabolism and damage in terms of necrosis. The resulting multiscale model of the liver was used to simulate perfusion-zonation-function relationships in the liver spanning scales from single cell to the lobulus. The model was applied to study the effects of (i) protein zonation patterns (metabolic zonation) and (ii) drug concentration dependence on spatially heterogeneous liver damage in the form of necrosis. Depending on the zonation pattern, different liver damage patterns could be reproduced, including periportal and pericentral necrosis as seen in drug-induced liver injury (DILI). Increasing the drug concentration led to an increase in the observed damage pattern. A key point for the success was the integration of domain-specific simulators based on standard exchange formats, i.e., libroadrunner for the high-performance simulation of ODE-based systems and FEBio for the simulation of the continuum-biomechanical part. This allows a standardized and reproducible exchange of cellular scale models in the Systems Biology Markup Language (SBML) between research groups.
Modulation of Temporoammonic-CA1 Synapses by Neuropeptide Y is Through Y1 Receptors
Authors: Cortes Mariana A. , Bartley Aundrea F. , Li Qin , Davis Taylor R. , Cunningham Stephen E. , Perez Patric J. , Dobrunz Lynn E.
Published: March 2024

The reduction of neuropeptide Y (NPY), an abundant neuromodulator in the brain, has been implicated in multiple neuropsychiatric disorders, such as depression and post-traumatic stress disorder (PTSD). The CA1 region of hippocampus is an important area for anxiety and highly expresses NPY. Injection of NPY into the CA1 is anxiolytic and has been shown to alleviate behavioral symptoms in a model of traumatic stress. It is known that activation of NPY Y1 receptors has anxiolytic effects and that NPY’s anxiolytic effects in CA1 are blocked by an NPY Y1 receptor antagonist. However, the location of Y1 receptors mediating NPY’s anxiolytic effects in CA1 is not yet known. CA1 receives inputs from entorhinal cortex through the temporammonic pathway (TA), which has been shown to be important for fear learning and sensitive to stress. Our lab previously showed that NPY reduces TA-evoked synaptic responses, however, the subtype of NPY receptor mediating this effect is not yet known. In this study, we show that Y1 receptors mediate the effects of both exogenous (bath-applied) and endogenously-released NPY in the TA pathway. This is the first demonstration of a Y1 receptor-mediated effect on synaptic function in CA1. Interestingly, chronic cell-type specific overexpression of NPY impairs the sensitivity of the TA pathway to NPY and the Y1 receptor agonist. However, the effect of NPY in the Schaffer collateral (SC) pathway, which is mediate by NPY Y2 receptors, is unaffected by NPY overexpression. There are pathway-specific differences in NPY receptors that modulate NPY’s effects in CA1 and respond differently to NPY overexpression. Our results demonstrating that NPY acts at Y1 receptors in the TA pathway are consistent with the idea that the TA pathway underlies the anxiolytic effects of NPY in CA1.
Daily rhythms in metabolic and locomotor behaviour of prematurely ageing PolgA mice
Authors: Singh Amit , Yilmaz Dilara , Wehrle Esther , Kuhn Gisela A. , Müller Ralph
Published: March 2024

Ageing is an inherent and intricate biological process that takes place in living organisms as time progresses. It involves the decline of multiple physiological functions, leading to body structure and overall performance modifications. The ageing process differs among individuals and is influenced by various factors, including lifestyle, environment, and genetic makeup. Metabolic changes and reduced locomotor activity are common hallmarks of ageing. Our study focuses on exploring these phenomena in prematurely ageing PolgA(D257A/D257A)mice (also known as PolgA) aged 41-42 weeks, as they closely mimic human ageing. We assess parameters such as oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), and locomotor activity using a metabolic cage for four days and comparing them with age-matched wild-type littermates (WT). Our findings revealed that VO2, VCO2, RER, locomotor activities, water intake, and feeding behaviour show a daily rhythm, aligning with roughly a 24-hour cycle. We observed that the RER was significantly increased in PolgA mice compared to WT mice during the night-time of the light-dark cycle, suggesting a shift towards a higher reliance on carbohydrate metabolism due to more food intake during the active phase. Additionally, female PolgA mice displayed a distinct phenotype with reduced walking speed, walking distance, body weight, and grip strength in comparison to male PolgA and WT mice, indicating an early sign of ageing. Taken together, our research highlights the impact of sex-specific patterns on ageing traits in PolgA mice aged 41-42 weeks, which may be attributable to human ageing phenotypes. The unique genetic composition and accelerated ageing characteristics of PolgA mice make them invaluable in ageing studies, facilitating the investigation of underlying biological mechanisms and the identification of potential therapeutic targets for age-related diseases.
Electroencephalographic Biomarkers of Relaxation: A Systematic Review and Meta-analysis
Authors: Sugimoto Kairi , Kurashiki Hideaki , Xu Yuting , Takemi Mitsuaki , Amano Kaoru
Published: March 2024

The human electroencephalogram (EEG) is composed of synchronous oscillations within characteristic frequency bands, including 8–13 Hz alpha oscillations that often appear during relaxation. Relaxation is critical for physical and mental health, but the extent to which various EEG components reflect relaxation remains uncertain. This systematic review and meta-analysis investigated associations between EEG components and concurrently measured reference indices of relaxation in healthy adults. A comprehensive database search and screening using preset criteria identified 38 studies involving 1,120 participants published between January 1940 and January 2022 for qualitative synthesis. These studies used various reference relaxation measures such as electrocardiographic indices related to parasympathetic nervous system activity and introspective indices obtained through questionnaires. Risks of bias were evaluated following the risk of bias assessment tool for nonrandomized studies. A meta-analysis of 23 studies using a random-effects model revealed positive correlations between relaxation index and the power of alpha oscillations at central channels (Fisher’sz-transformed correlation coefficient and [95% confidence interval]: 0.23 [0.10–0.36]) and frontal channels (0.16 [0.02–0.31]). The correlation was significantly higher for the central channel compared with other channels. No significant correlations were detected between relaxation indices and other EEG frequencies or channels. The causal relationships between relaxation and alpha power at central and frontal channels warrant further study.
Conserved jumbo phage factors required for protein import into a phage nucleus
Authors: Kokontis Claire , Klein Timothy A , Silas Sukrit , Bondy-Denomy Joseph
Published: March 2024

Bacteriophages use diverse mechanisms to evade anti-phage defenses systems. ΦKZ-like jumbo phages assemble a proteinaceous nucleus-like compartment that excludes antagonistic host nucleases, while internalizing DNA replication and transcription machinery1,2,3,4. The phage factors required for protein import and the mechanisms of selectivity remain unknown, however. Here, we uncover an import system composed of proteins highly conserved across nucleus-forming phages, together with additional cargo-specific contributors. Using a genetic selection that forces the phage to decrease or abolish import of specific proteins, we determine that the import of five different phage nuclear-localized proteins (Nlp) all require distinct interfaces of the same factor, Imp1 (gp69). Imp1 forms discrete puncta in the phage nuclear periphery likely in complex with a direct interactor Imp6 (gp67), a conserved protein encoded nearby. The import of some proteins, including a host topoisomerase (TopA), additionally require Imp3 (gp59), a factor required for proper Imp1 function. Three additional phage proteins (Imp2, Imp4, Imp5) are also required for the import of two queried nuclear cargos, perhaps acting as specific adaptors. We therefore propose a core import system including Imp1, Imp3, and Imp6 with the highly selective Imp1 protein licensing transport through a protein lattice.
Insufficiency of 40S ribosomal proteins, RPS26 and RPS25, negatively affects biosynthesis of polyglycine-containing proteins in fragile-X associated conditions
Authors: Tutak Katarzyna , Broniarek Izabela , Zielezinski Andrzej , Niewiadomska Daria , Skrzypczak Tomasz , Baud Anna , Sobczak Krzysztof
Published: March 2024

Expansion of CGG repeats (CGGexp) in the 5’ untranslated region (5’UTR) of theFMR1gene underlies the fragile X premutation-associated conditions including tremor/ataxia syndrome, a late-onset neurodegenerative disease and fragile X-associated primary ovarian insufficiency. One common pathomechanism of these conditions is the repeat-associated non-AUG-initiated (RAN) translation of CGG repeats of mutantFMR1mRNA, resulting in production of FMRpolyG, a toxic protein containing long polyglycine tract. To identify novel modifiers of RAN translation we used an RNA-tagging system and mass spectrometry-based screening. It revealed proteins enriched on CGGexp-containingFMR1RNA in cellulo, including a ribosomal protein RPS26, a component of the 40S subunit. We demonstrated that depletion of RPS26 and its chaperone TSR2, modulates FMRpolyG production and its toxicity. We also found that the RPS26 insufficiency impacted translation of limited number of proteins, and 5’UTRs of mRNAs encoding these proteins were short and guanosine and cytosine-rich. Moreover, the silencing of another component of the 40S subunit, the ribosomal protein RPS25, also induced repression of FMRpolyG biosynthesis. Results of this study suggest that the two 40S ribosomal proteins and chaperone TSR2 play an important role in noncanonical CGGexp-related RAN translation.
Proliferative cell targeting and epithelial cell turnover fuels hepatitis E virus replication in human intestinal enteroids
Authors: Santos-Ferreira Nanci , Zhang Xin , Corneillie Laura , Van Dycke Jana , Chiu Winston , Montpellier Claire , Neyts Johan , Cocquerel Laurence , Kaptein Suzanne J. F. , Rocha-Pereira Joana
Published: March 2024

Hepatitis E virus (HEV) is a leading pathogen causing acute viral hepatitis globally. While HEV is primarily spread fecal-orally, the role of the gut in HEV pathogenesis remains largely unexplored, including how HEV disseminates from gut to liver, and whether the gut is an HEV reservoir. We here aimed to illuminate HEV biology in the gut using human intestinal enteroids (HIEs).

Three strategies were explored to establish an HEV-HIE model: three-dimensional (3D) HIEs, two-dimensional (2D) HIEs in transwell, and HEV RNA-electroporated HIEs. HEV particles produced by electroporated HIEs were characterized by western blot and gradient centrifugation. The intestinal tropism of HEV was investigated through confocal fluorescent microscopy and gene expression analysis.

HEV infection in 3D-HIEs and 2D-HIEs showed limited replication, whereas HIEs electroporation led to a sustained increase in the release of non-enveloped infectious virions. These virions could re-infect new 3D-HIEs, yielding a ∼2 log10increase in HEV RNA. In electroporated HIEs, high expression of the infectious ORF2 capsid form was observed in the supernatant. Importantly, 70% of all HEV-infected cells were identified as proliferative cells. ORF2 staining was also observed in absorptive enterocytes, goblet, and enteroendocrine cells.

Overall, we established a robust HEV-HIE model that yields high titers of infectious non-enveloped virions. Proliferative cells and the fast intestinal epithelial cell turnover are important features that facilitate efficient HEV replication, and likely also its dissemination. This study suggests that the gut is an HEV reservoir, capable of producing some of the non-enveloped HEV shed in the feces.

Significance

Hepatitis E virus (HEV) causes ∼20 million enterically transmitted cases of viral hepatitis globally. To better understand the largely unexplored role of the gut during an HEV infection, we used human intestinal enteroids (HIEs). We show that HEV-electroporated HIEs produce highly infectious non-envelopedHEV particles, resulting in a more efficient re-infection compared with traditional gold-standard methods. Importantly, we detected HEV in multiple human intestinal epithelial cell types within the human intestinal epithelium, with the majority of proliferative cells infected. This model offers valuable insights into the intestinal tropism of HEV and can serve to further investigate chronic HEV infection in the gut. Moreover, this underscores the importance of using physiologically relevant models to unravel details of HEV infection in the gut.
Astrocytic metabolic control of orexinergic activity in the lateral hypothalamus regulates sleep and wake architecture
Authors: Braga Alice , Chiacchiaretta Martina , Pellerin Luc , Kong Dong , Haydon Philip G.
Published: March 2024

Neuronal activity undergoes significant changes during vigilance states, accompanied by an accommodation of energy demands. While the astrocyte-neuron lactate shuttle has shown that lactate is the primary energy substrate for sustaining neuronal activity in multiple brain regions, its role in regulating sleep/wake architecture is not fully understood. We manipulated the cell-specific expression of monocarboxylate transporters (MCTs), the major lactate transporters, to examine the involvement of astrocytic lactate supply in maintaining consolidated wakefulness. Our results demonstrate that reduced expression of MCT4 in astrocytes disrupts lactate supply to orexin neurons in the lateral hypothalamus (LH), impairing wakefulness stability. We also show that MCT2-mediated lactate uptake is necessary for maintaining tonic firing of orexinergic neurons and stabilizing wakefulness. Our findings provide bothin vivoandin vitroevidence supporting the critical role of astrocyte-to-orexinergic neuron lactate shuttle in regulating proper sleep/wake stability— a crucial step for maintaining physiological functions and overall well-being.
Characterization of West Nile virus Koutango lineage from Phlebotomine Sandflies in Kenya 2021
Authors: Thiiru Jane Wambui , Langat Solomon , Mulwa Francis , Cinkovich Stephanie , Koka Hellen , Yalwala Santos , Khamadi Samoel , Onguso Justus , Odemba Nicholas , Ngere Francis , Johnson Jaree , Egbo Timothy , Garges Eric , Ojwang Elly , Eyase Fredrick
Published: March 2024

The West Nile virus (WNV), primarily transmitted by mosquitoes, is one of the most widespread flaviviruses globally, with past outbreaks occurring in the USA and Europe. Recent studies in parts of Africa, including Kenya, have identified the West Nile virus Koutango lineage (WN-KOUTV) among phlebotomine sandfly populations, however, our understanding of this virus remains limited. Hence, this study aimed to characterize WN-KOUTV from phlebotomine sandflies. Sandflies were sampled between 12-16thMarch 2021 from six villages in Baringo South, Kenya, using CDC light traps. Female sandflies were taxonomically identified and pooled based on genus. Virus isolation was performed in Vero cells. Viral genome was determined using next-generation sequencing. Phylogenetic and molecular clock analyses were done to decipher the virus’s evolutionary relationships. Comparative analyses of amino acid sequences were performed to determine variations. Protein modeling in Pymol was conducted to elucidate variations in key protein regions. Evolutionary pressure analysis investigated the selection pressures on the virus.In vitroexperiments were done to investigate the virus growth kinetics in mammalian (Vero-E6) and mosquito (C636) cells. We report the isolation of WN-KOUTV from Salabani Baringo South, Kenya. The isolated WN-KOUTV clustered with previously identified WN-KOUTV strains. Comparative analysis revealed unique amino acid at NS5 653. Diversifying pressure was acting NS3 267 of the WN-KOUTV lineage. WN-KOUTV replicates efficiently in Vero-E6 and C636 cells comparable to West Nile virus Lineage 1a, isolated from mosquitoes. The isolation of WN-KOUTV in sandflies points to them as potential vectors, however, vector competence studies would confirm this. The efficient replication in mammalian and mosquito cell lines elucidated its adaptability to host and vector. We speculate the close genetic relationship of WN-KOUTV strains is enabled by the bird migratory route between East and West Africa. If proven, this may point to a potential future pandemic pathway for this virus.
Zika Virus Infection Knowledge and Communication Preferences Among Women of Reproductive Age in Central Brooklyn, New York: A Thematic Analysis
Authors: Dowling Russell , Kolokotronis Sergios-Orestis , Thompson Azure B.
Published: March 2024

The 2016 outbreak of Zika virus (ZIKV) infected millions and resulted in thousands of infants born with malformations. Though the clusters of severe birth defects resulting from this outbreak have subsided, ZIKV continues to be a concern throughout much of Latin America and the Caribbean. Travel and sexual intercourse remain the dominant transmission risk factors for women of reproductive age and their partners. This is particularly true for communities in Brooklyn, New York, that comprise large immigrant and foreign-born populations. Practitioners of public health understand little about how women at risk for ZIKV are most likely to receive information about the virus or who they trust most to provide that information. In the context of five focus group discussions, this study explored the knowledge and communication preferences of 20 women of reproductive age in Central Brooklyn. Results derived from a thematic analysis suggest that while most women are familiar with mosquitos as ZIKV vectors, knowledge of sexual transmission is considerably lower. Many respondents believe that only women who are pregnant or trying to become pregnant are at risk, and public health agencies, such as the U.S. Centers for Disease Control and Prevention, remain the most trusted sources of information. These findings can support more effective communication about the risks of ZIKV infection and other vector-borne diseases to women in New York City and similar urban communities.
Adolescent Dating and HIV Perceptions: A Phenomenological Study in N’Djamena, Chad
Authors: Bedingar Esias , Bedingar Ngarossorang , Seli Djimet , Sudfeld Christopher
Published: March 2024

Introduction

The study focuses on understanding the complex interplay between dating behaviors and HIV perceptions among adolescents and young people (ages 15-24 years) in Chad. As adolescents and young people are disproportionately affected by the HIV epidemic, this research aims to uncover how cultural and social influences shape young people’s attitudes towards dating and HIV prevention. The significance of this study lies in its potential to inform targeted, culturally sensitive HIV prevention strategies for the youth in Chad.

Methods

A qualitative phenomenological approach was adopted, using 4 focus group discussions (n=12 each) with high school students in N’Djamena, Chad. Participants were divided into beneficiary and non-beneficiary groups based on their exposure to a peer education program about HIV. Data analysis was conducted using ATLAS.ti software and the descriptive Colaizzi method, ensuring a comprehensive understanding of participants’ perspectives.

Results

Findings revealed significant gender differences in dating motivations and partner selection criteria. While males primarily viewed dating as a means to fulfill sexual desires, females often sought emotional connection and companionship. There was a general lack of awareness about PrEP, with more emphasis on condom use for pregnancy prevention rather than HIV or STI protection. Gender roles played a substantial part in decisions regarding safe sex practices, with a notable discrepancy in shared versus individual responsibility. Additionally, risk behaviors like alcohol use and multiple partnerships were identified as prevalent among youth.

Conclusions

The study highlights the need for gender-sensitive educational interventions focusing on the realities of adolescent sexual behavior in Chad. It underscores the disparity in HIV knowledge and prevention awareness among adolescents, pointing out the absence of awareness about PrEP. Future research should emphasize developing HIV prevention strategies that resonate with the unique cultural and social dynamics of Chadian youth, considering their specific dating behaviors and perceptions towards HIV.
Endothelial calcium firing mediates extravasation of metastatic tumor cells
Authors: Peralta Marina , Dupas Amandine , Larnicol Annabel , Lefebvre Olivier , Goswami Ruchi , Stemmelen Tristan , Molitor Anne , Carapito Raphael , Girardo Salvatore , Osmani Naël , Goetz Jacky G.
Published: March 2024

Metastatic dissemination is driven by genetical, biochemical and biophysical cues that favor the distant colonization of organs and the formation of life-threatening secondary tumors. We have previously demonstrated that endothelial cells (ECs) actively remodel during extravasation by enwrapping arrested tumor cells (TCs) and extrude them from the vascular lumen while maintaining perfusion. In this work, we dissect the cellular and molecular mechanisms driving endothelial remodeling. Using high-resolution intravital imaging in zebrafish embryos, we demonstrate that the actomyosin network of ECs controls tissue remodeling and subsequent TC extravasation. Furthermore, we uncovered that this cytoskeletal remodeling is driven by altered endothelial- calcium (Ca2+) signaling caused by arrested TCs. Accordingly, we demonstrated that inhibition of voltage-dependent calcium L-type channels impairs extravasation. Lastly, we identified P2X4, TRP, and Piezo1 mechano-gated Ca2+channels as key mediators of the process. These results further highlight the central role of endothelial remodeling during extravasation of TCs and open avenues for successful therapeutic targeting.

Graphical Abstract
An evolutionary cell biology perspective into the diverging mechanisms of clathrin-mediated endocytosis in dikarya fungi
Authors: Picco Andrea , Toret Christopher P. , Rivier-Cordey Anne-Sophie , Kaksonen Marko
Published: March 2024

Clathrin-mediated endocytosis is an ancient eukaryotic trafficking pathway, which transports plasma membrane and associated cargo into the cell and is involved in numerous cell- and tissue-level processes. Cargo selection and clathrin-coated vesicle formation is mediated by over 60 proteins that assemble in a regular and sequential manner at the plasma membrane. Decades of endocytosis studies have followed the tenet that uncovering the conserved core molecular mechanisms is sufficient to understand a cellular process. However, this approach also revealed a number of cell type or species-related variations that challenge a universal conserved, core mechanism. In this paper, we refocus on the endocytic diversity to understand how evolution shapes endocytic mechanisms. We define a comparative evolutionary cell biology approach that uses dikarya fungi as a model clade and live-cell fluorescence microscopy to study endocytosis dynamics in three species:Saccharomyces cerevisiae,Schizosaccharomyces pombeandUstilago maydis. Our results quantitatively define several phenotypic differences between the species. We uncover several differences that impact the endocytic early phase, the protein assembly order, actin regulation, membrane invagination and scission. These findings demonstrate a mosaic evolution of endocytic traits, suggest ancestral states and direction of changes. We also investigate the phenotypic plasticity and robustness against environmental conditions. Lastly, we demonstrate that relatively minor evolutionary changes can majorly impact endocytic phenotypes. These studies force an appreciation of endocytic variation as not auxiliary, but vital to mechanistic understanding of this conserved cellular pathway.
Plasma Proteomics of Genetic Brain Arteriosclerosis and Dementia Syndrome Identifies Signatures of Fibrosis, Angiogenesis, and Metabolic Alterations
Authors: Keller Jonah N. , Radabaugh Hannah , Karvelas Nikolaos , Fitzsimons Stephen , Treiman Scott , Palafox Maria F. , McDonnell Lisa , Quiroz Yakeel T. , Lopera Francisco J. , Banerjee Debarag , Wang Michael M. , Arboleda-Velasquez Joseph F. , Meschia James F. , Ferguson Adam R. , Elahi Fanny M.
Published: March 2024

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of vascular cognitive impairment and dementia. A genetic arteriolosclerotic disease, the molecular mechanisms driving vascular brain degeneration and decline remain unclear. With the goal of driving discovery of disease-relevant biological perturbations in CADASIL, we used machine learning approaches to extract proteomic disease signatures from large-scale proteomics generated from plasma collected from three distinct cohorts in US and Colombia: CADASIL-Early (N= 53), CADASIL-Late (N= 45), and CADASIL-Colombia (N= 71). We extracted molecular signatures with high predictive value for early and late-stage CADASIL and performed robust cross- and external-validation. We examined the biological and clinical relevance of our findings through pathway enrichment analysis and testing of associations with clinical outcomes. Our study represents a model for unbiased discovery of molecular signatures and disease biomarkers, combining non-invasive plasma proteomics with clinical data. We report on novel disease-associated molecular signatures for CADASIL, derived from the accessible plasma proteome, with relevance to vascular cognitive impairment and dementia.
Exhaustion profile on classical monocytes after LPS stimulation in patients with Crohn’s disease
Authors: Oliveira Lucas Pires Garcia , Xavier Rafaela Gomes , Nora Claudia Concer Viero , Mangueira Cristóvão Luis Pitangueira , Rosseto Eliane Aparecida , Aloia Thiago , Gil Jaime Zaladek , Neto Arceu Scanavini , Lopes Filipa Blasco Tavares Pereira , Carvalho Karina Inacio
Published: March 2024

Crohn’s disease is an inflammatory bowel disease that induces diarrhea, abdominal pain, weight loss, and even susceptibility to developing tumors. The immune system is pivotal in the gastrointestinal tract, promoting tolerance against commensal antigens and food. However, Crohn’s disease manifests by a breakdown in the mechanism of immune tolerance and the consequent development of exacerbated chronic inflammatory responses. The involvement of the immune system is pivotal in Crohn’s disease, with a wide range of immune cells being altered, which may include monocytes. Taking the lack of knowledge regarding monocytes in Crohn’s disease, we ought to elucidate the cytokine production and activation profile of monocyte subsets in the pathophysiology. We used multiparametric flow cytometry, quantified gene expression using qPCR, and made a correlation matrix regarding flow cytometry data and qPCR using a bioinformatic approach to examine monocyte status. The Corhn’s patients show a decrease in all subsets of monocytes.

In contrast, classical monocytes show an exhaustion profile with increased expression of CD38 and decreased production of IL-1β after LPS stimulation in the patients’ group. These results indicate that monocyte subsets are differentially involved in the pathophysiology. These findings may suggest that monocytes favor disease chronicity and lack immune response resolution.
Proteome dynamics reveal Leiomodin 1 as a key regulator of myogenic differentiation
Authors: Späth Ellen , Schüler Svenja C. , Heinze Ivonne , Dau Therese , Minetti Alberto , Hofmann Maleen , Maltzahn Julia von , Ori Alessandro
Published: March 2024

During myogenic differentiation the cellular architecture and proteome of muscle stem cells and myoblasts undergo extensive remodeling. These molecular processes are only partially understood and display alterations in disease conditions as well as during aging resulting in impaired regeneration. Here, we used mass spectrometry to quantify the temporal dynamics of more than 6000 proteins during myogenic differentiation. We identified the actin nucleator leiomodin 1 (LMOD1) among a restricted subset of cytoskeletal proteins increasing in abundance in early phases of myogenic differentiation. We show that LMOD1 is already expressed by muscle stem cellsin vivoand displays increased abundance during skeletal muscle regeneration, especially during early regeneration suggesting that LMOD1 is important for induction of myotube formation. Of note, knockdown of LMOD1 in primary myoblasts and during skeletal muscle regeneration severely affects myogenic differentiation, while overexpression accelerates and improves the formation of myotubes suggesting that LMOD1 is a critical component regulating myogenic differentiation. Mechanistically, we show that LMOD1 physically and functionally interacts with the deacetylase sirtuin1 (SIRT1), a regulator of myogenic differentiation, especially at the onset of myogenic differentiation. We demonstrate that LMOD1 influences SIRT1 localization and the expression of a subset of its target genes. Consistently, depletion or pharmacological inhibition of SIRT1 partially rescues the impairment of myogenic differentiation observed after knockdown of LMOD1. Our work identifies a new regulator of myogenic differentiation that might be targeted to improve muscle regeneration in aging and disease.
Comparison of the tolerability of161Tb- and177Lu-labeled somatostatin analogues in the preclinical setting
Authors: Busslinger Sarah D. , Mapanao Ana Katrina , Kegler Kristel , Bernhardt Peter , Flühmann Fabienne , Fricke Julia , Zeevaart Jan Rijn , Köster Ulli , van der Meulen Nicholas P. , Schibli Roger , Müller Cristina
Published: March 2024

Purpose

[177Lu]Lu-DOTATATE is an established somatostatin receptor (SSTR) agonist for the treatment of metastasized neuroendocrine neoplasms, while the SSTR antagonist [177Lu]Lu-DOTA-LM3 has only scarcely been employed in clinics. Impressive preclinical data obtained with [161Tb]Tb-DOTA-LM3 in tumor-bearing mice indicated the potential of terbium-161 as an alternative to lutetium-177. The aim of the present study was to compare the tolerability of161Tb- and177Lu-based DOTA-LM3 and DOTATATE in immunocompetent mice.

Methods

Dosimetry calculations were performed based on biodistribution data of the radiopeptides in immunocompetent mice. Treatment-related effects on blood cell counts were assessed on Days 10, 28 and 56 after application of [161Tb]Tb-DOTA-LM3 or [161Tb]Tb-DOTATATE at 20 MBq per mouse. These radiopeptides were also applied at 100 MBq per mouse and the effects compared to those observed after application of the177Lu-labeled counterparts. Bone marrow smears, blood plasma parameters and organ histology were assessed at the end of the study.

Results

The absorbed organ dose was commonly higher for the SSTR antagonist than for the SSTR agonist and for terbium-161 over lutetium-177. Application of a therapeutic activity level of 20 MBq [161Tb]Tb-DOTA-LM3 or [161Tb]Tb-DOTATATE was well tolerated without major hematological changes. The injection of 100 MBq of the161Tb- and177Lu-based somatostatin analogues affected the blood cell counts, however. The lymphocytes were 40-50% lower in treated mice compared to the untreated controls on Day 10 irrespective of the radionuclide employed. At the same timepoint, thrombocyte and erythrocyte counts were 30–50% and 6–12% lower, respectively, after administration of the SSTR antagonist (p<0.05) while changes were less pronounced in mice injected with the SSTR agonist. All blood cell counts were in the normal range on Day 56. Histological analyses revealed minimal abnormalities in the kidneys, liver and spleen of treated mice. No correlation was observed between the organ dose and frequency of the occurrence of abnormalities.

Conclusion

Hematologic changes were more pronounced in mice treated with the SSTR antagonist than in those treated with the SSTR agonist. Despite the increased absorbed dose delivered by terbium-161 over lutetium-177, [161Tb]Tb-DOTA-LM3 and [161Tb]Tb-DOTATATE should be safe at activity levels that are recommended for their respective177Lu-based analogues.
Temperature dependence of the Ge(111) surface electronic structure probed by inelastic H atom scattering
Authors: Krüger Kerstin , Hertl Nils , Wodtke Alec M. , Bünermann Oliver
Published: March 2024

Experimental methods capable of determining the electronic properties of the surfaces of materials suffer from severe limitations, including interference from bulk electronic states, insensitivity to unoccupied states, and the requirement that the material be conducting. In this work, we introduce inelastic H atom scattering as a tool to probe the electronic structures of surfaces, which can be applied to both conducting and nonconducting samples while exhibiting exceptional surface sensitivity. We illustrate the method for the example of Ge(111). The measurements show a semiconducting surface at low temperature that continuously becomes increasingly metallic at high temperature.

©2024 American Physical Society
2024
American Physical Society
Changing person-environment fit among underrepresented undergraduate physics students: Successes from a small department
Authors: Kim Ann Y. , Ton Vina , Vega Daniel
Published: March 2024

Female students, Latinx students, first-generation students, and transfer students often feel uncomfortable in science, technology, engineering, and mathematics (STEM) environments. However, some departments have been making progress in changing that. Guided by double consciousness and person-environment fit theory, we investigated the lived experiences of historically marginalized undergraduate and masters-level physics students at a large state university to understand how this particular department provides an environment encouraging all students they fit in physics. Graduated students and faculty were interviewed from California State University, Long Beach. Through the interviews, we gained an understanding of significant student experiences and their perceptions of fit in this physics environment. Department community members perceived the department environment to be open, which contributed to broadening fit and supporting diverse students to thrive. The importance of faculty agency in creating a welcoming and supportive physics environment is highlighted. Finally, we found students in this department take with them an approach to physics that they see applicable to other areas of study and their lives. We called this a physics state of mind. We include suggestions for other STEM departments based on the findings and previous research.

Published by the American Physical Society
2024
Universal determination of comagnetometer response to spin couplings
Authors: Padniuk Mikhail , Klinger Emmanuel , Łukasiewicz Grzegorz , Gavilan-Martin Daniel , Liu Tianhao , Pustelny Szymon , Jackson Kimball Derek F. , Budker Dmitry , Wickenbrock Arne
Published: March 2024

We propose and demonstrate a general method to calibrate the frequency-dependent response of self-compensating noble-gas–alkali-metal comagnetometers to arbitrary spin perturbations. This includes magnetic and nonmagnetic perturbations such as rotations and exotic spin interactions. The method is based on a fit of the magnetic field response to an analytical model. The frequency-dependent response of the comagnetometer to arbitrary spin perturbations can be inferred using the fit parameters. We demonstrate the effectiveness of this method by comparing the inferred rotation response to an experimental measurement of the rotation response. Our results show that experiments relying on zero-frequency calibration of the comagnetometer response can over- or underestimate the comagnetometer sensitivity by orders of magnitude over a wide frequency range. Moreover, this discrepancy accumulates over time as operational parameters tend to drift during comagnetometer operation. The demonstrated calibration protocol enables accurate prediction and control of comagnetometer sensitivity to, for example, ultralight bosonic dark-matter fields coupling to electron or nuclear spins, as well as accurate monitoring and control of the relevant system parameters.

Published by the American Physical Society
2024
Measurements of the geometrical characteristics and refractive index of specimens made with X-ray interferometers
Authors: Mkrtchyan Vahram , Aivazyan Ashot , Petrosyan Sargis , Balyan Minas
Published: March 2024

The theoretical background to the formation of interference fringes in a triple Laue X-ray interferometer by a specimen having plano-concave form is presented. The interference fringes in the general case have an elliptical form. The relation between the radius of the specimen, the refractive index and the radii of the interference fringes is established. For two epoxy lenses having different radii, the interference fringes are registered. The refractive index and the radii are determined by measuring the radii of the obtained interference fringes.
An improved protection of alanine for atmospheric corrosion of mild steel using carbon dots-montmorillonite hybrid materials
Authors: Ma Liang , Wang Qiang , Yang Haini , Zhang Da Quan , Wu Wei
Published: March 2024

Purpose

The aim of this paper is to solve the toxic and harmful problems caused by traditional volatile corrosion inhibitor (VCI) and to analyze the effect of the layered structure on the enhancement of the volatile corrosion inhibition prevention performance of amino acids.

Design/methodology/approach

The carbon dots-montmorillonite (DMT) hybrid material is prepared via hydrothermal process. The effect of the DMT-modified alanine as VCI for mild steel is investigated by volatile inhibition sieve test, volatile corrosion inhibition ability test, electrochemical measurement and surface analysis technology. It demonstrates that the DMT hybrid materials can improve the ability of alanine to protect mild steel against atmospheric corrosion effectively. The presence of carbon dots enlarges the interlamellar spacing of montmorillonite and allows better dispersion of alanine. The DMT-modified alanine has higher volatilization ability and an excellent corrosion inhibition of 85.3% for mild steel.

Findings

The DMT hybrid material provides a good template for the distribution of VCI, which can effectively improve the vapor-phase antirust property of VCI.

Research limitations/implications

The increased volatilization rate also means increased VCI consumption and higher costs.

Practical implications

Provides a new way of thinking to replace the traditional toxic and harmful VCI.

Originality/value

For the first time, amino acids are combined with nano laminar structures, which are used to solve the problem of difficult volatilization of amino acids.
The role of green innovation in the relationship between green HRM practices and sustainable business performance; evidence from the mining industry
Authors: Suleman Abdul-Razak , Kyei-Frimpong Michael , Akwetey-Siaw Bridget
Published: March 2024

Purpose

Drawing on the natural resource-based view (NRBV) theory, the study aimed to examine the mediating role of green innovation (GI) in the nexus between green human resource management practices (Green HRMPs) and sustainable business performance (SBP).

Design/methodology/approach

This study adopted the descriptive time-lagged research design. Data were collected from 278 managerial staff of five mining companies in Ghana at different waves within a 3-month interval. Descriptive and inferential statistics were used to analyse the data received using the statistical package for the social sciences (SPSS) statistics (V. 26.0) and Smart PLS (V.4.0).

Findings

The study found that Green HRMPs significantly related more to economic performance (EP) than social performance (SP) but did not significantly relate to environmental performance (EnP). Moreover, the results revealed that GI partially mediated the nexus between Green HRMPs and both SP and EP but fully mediated the link between Green HRMPs and EnP.

Originality/value

The relevance of Green HRMPs in ensuring corporate sustainability has been largely established in the extant literature. However, there is an evidential dearth of studies in the literature concerning the mediating role of GI in the nexus between Green HRMPs and SBP, especially in developing economies context. Hence, this study serves as a significant contributing card from Ghana by advancing the NRBV theory.
Consumer visual attention to food allergen information on restaurant menus: an eye-tracking study
Authors: Lee Yee Ming , Wei Chunhao (Victor)
Published: March 2024

Purpose

This study sought to understand which food allergen labeling systems (non-directive, semi-directive, and directive) were attended to and preferred by 34 participants with food hypersensitivity and their perceived corporate social responsibility (CSR) and behavioral intention towards a restaurant that identifies food allergens on menus.

Design/methodology/approach

This study used an online survey with open-ended and ranking questions, combined with eye-tracking technology, to explore participants' visual attention and design preferences regarding four menus. This study utilized one-way repeated measures analysis of variance (RM-ANOVA) and heat maps to analyze participants' menu-reading behaviors. A content analysis of survey responses and a ranking analysis of menus were conducted to understand the reasons behind consumers' preferred menu designs.

Findings

The advisory statement was not much attended to. Participants identified food allergen information significantly quicker with the directive labeling system (icons) than the other two systems, implying they were eye-catching. Semi-directive labeling system (red text) has lower visit count and was more preferred than two other systems; each labeling system has its strengths and limitations. Participants viewed restaurants that disclosed food allergen information on menus as socially responsible, and they would revisit those restaurants in the future.

Originality/value

This study was one of the first to explore, through use of eye-tracking technology, which food allergen labeling systems were attended to by consumers with food hypersensitivity. The use of triangulation methods strengthened the credibility of the results. The study provided empirical data to restauranteurs in the US on the values of food allergen identification on restaurant menus, although it is voluntary.