bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivomarker of brainstem myelin is associated to quantitative sleep parameters in healthy young men
Authors: Talwar Puneet , Deantoni Michele , Van Egroo Maxime , Muto Vincenzo , Chylinski Daphne , Koshmanova Ekaterina , Jaspar Mathieu , Meyer Christelle , Degueldre Christian , Berthomier Christian , Luxen André , Salmon Eric , Collette Fabienne , Dijk D.-J. , Schmidt Christina , Phillips Christophe , Maquet Pierre , Sherif Siya , Vandewalle Gilles 
Published: July 2023

AbstractBrain structural integrity has been suggested to contribute to the variability in human sleep quality and composition. The associations between sleep parameters and the regional integrity of subcortical structures implicated in sleep-wake regulation remain, however, largely unexplored. The present study aimed at assessing association between quantitative Magnetic Resonance Imaging (qMRI)-derived marker of the myelin content of the brainstem with the variability in the sleep electrophysiology in a large sample of healthy young men (N=321;∼22y). Generalized Additive Model for Location, Scale and Shape (GAMLSS) was used to seek associations between sleep metrics and Magnetisation Transfer saturation (MTsat) qMRI values, proxy for myelin content. Separate GAMLSS revealed that sleep onset latency and slow wave sleep intensity were significantly associated with MTsat-derived myelin estimates in the brainstem (pcorrected≤.03), with overall higher MTsat value associated with values reflecting better sleep quality. The association changed with age, however (MTsat-by-age interaction - pcorrected≤.03), with higher MTsat value linked to better values in the two sleep metrics in the individuals of our sample aged ∼18 to 20y. Similar associations were detected across different parts of the brainstem (pcorrected≤.03), suggesting that the overall maturation and integrity of the brainstem was associated with both sleep metrics. Our results suggest that myelination of the many reticular nuclei of the brainstem essential to regulation of sleep is associated with inter-individual differences in sleep characteristics during early adulthood. They may have implications for sleep disorders or neurological diseases related to myelin.
Phase separation of ecDNA aggregates establishesin-transcontact domains boosting selectiveMYCregulatory interactions
Authors: Conte Mattia , Matteuzzi Tommaso , Esposito Andrea , Chiariello Andrea M. , Bianco Simona , Vercellone Francesca , Nicodemi Mario 
Published: July 2023

AbstractExtrachromosomal DNAs (ecDNAs) are found in the nucleus of an array of human cancer cells where they can form clusters that were associated to oncogene overexpression, as they carry genes andcis-regulatory elements. Yet, the mechanisms of aggregation and gene amplification beyond copy-number effects remain mostly unclear. Here, we investigate, at the single molecule level,MYC-harboring ecDNAs of COLO320-DM colorectal cancer cells by use of a minimal polymer model of the interactions of ecDNA BRD4 binding sites and BRD4 molecules. We find that BRD4 induces ecDNAs phase separation, resulting in the self-assembly of clusters whose predicted structure is validated against HiChIP data (Hung et al., 2021). Clusters establishin-transassociated contact domains (I-TADs) enriched, beyond copy number, in regulatory contacts among specific ecDNA regions, encompassing itsPVT1-MYCfusions but not its other canonicalMYCcopy. That explains why the fusions originate most of ecDNAMYCtranscripts (Hung et al., 2021), and shows that ecDNA clusteringper seis important but not sufficient to amplify oncogene expression beyond copy-number, reconciling opposite views on the role of clusters (Hung et al., 2021; Zhu et al., 2021; Purshouse et al. 2022). Regulatory contacts become strongly enriched as soon as half a dozen ecDNAs aggregate, then saturate because of steric hindrance, highlighting that even cells with few ecDNAs can experience pathogenicMYCupregulations. To help drug design and therapeutic applications, with the model we dissect the effects of JQ1, a BET inhibitor. We find that JQ1 reverses ecDNA phase separation hence abolishing I-TADs and extra regulatory contacts, explaining how in COLO320-DM cells it reducesMYCtranscription (Hung et al., 2021).
Three-step docking by WIPI2, ATG16L1 and ATG3 delivers LC3 to the phagophore
Authors: Rao Shanlin , Strong Lisa M. , Ren Xuefeng , Skulsuppaisarn Marvin , Lazarou Michael , Hurley James H. , Hummer Gerhard 
Published: July 2023

AbstractThe covalent attachment of ubiquitin-like LC3 proteins prepares the autophagic membrane for cargo recruitment. We resolve key steps in LC3 lipidation by combining molecular dynamics simulations and experimentsin vitroandin cellulo. We show how the E3-like ligase ATG12– ATG5-ATG16L1 in complex with the E2-like conjugase ATG3 docks LC3 onto the membrane in three steps by (1) the PI(3)P effector protein WIPI2, (2) helix α2 of ATG16L1, and (3) a membrane-interacting surface of ATG3. Phosphatidylethanolamine (PE) lipids concentrate in a region around the thioester bond between ATG3 and LC3, highlighting residues with a possible role in the catalytic transfer of LC3 to PE, including two conserved histidines. In a near-complete pathway from the initial membrane recruitment to the LC3 lipidation reaction, the three-step targeting of the ATG12–ATG5-ATG16L1 machinery establishes a high level of regulatory control.
Non-cell autonomous cardiomyocyte regulation complicates gene supplementation therapy forLMNAcardiomyopathy
Authors: Sun Yueshen , Guo Congting , Chen Zhan , Lin Junsen , Yang Luzi , Zhang Yueyang , Wu Chenyang , Zhao Dongyu , Jardin Blake , Pu William T. , Zhao Mingming , Dong Erdan , Hu Xiaomin , Zhang Shuyang , Guo Yuxuan 
Published: July 2023

AbstractAimsRecombinant adeno-associated viruses (rAAVs) are federally approved gene delivery vectors for in vivo gene supplementation therapy. Loss-of-function truncating variants ofLMNA, the coding gene for Lamin-A/C, are one of the primary causes of inherited dilate cardiomyopathy (DCM). Here we aim to study whether AAV-basedLMNAsupplementation could treatLMNAdeficiency-triggered cardiac defects.Methods and ResultsWe compared whole-body, cardiomyocyte-specific and genetic-mosaic mouse models that carryLmnatruncating variants at the same genetic loci and uncovered primarily a non-cell autonomous impact ofLmnaon cardiomyocyte maturation. Whole-body lamin-A supplementation by rAAVs moderately rescued the cardiac defects inLmnagermline mutants. By contrast, cardiomyocyte-specific lamin-A addback failed to restore the cardiomyocyte growth defects. A Cre-loxP-based AAV vector that expresses lamin-A throughout the body but excluding the heart was able to restore cardiomyocyte growth inLmnagermline mutants.ConclusionsLmnaregulates cardiomyocyte growth non-cell autonomously. Non-myocytes are the key cell targets for a successful gene therapy forLMNA-associated cardiac defects.Translational perspectiveLMNAtruncating mutations are among the major causes of inherited DCM. AAV gene supplementation therapy is emerging as a promising strategy to treat genetic cardiomyopathy, but whether this strategy is suitable forLMNAcardiomyopathy remained unclear. Our study counterintuitively showed that the cardiomyocytes are not necessarily the correct therapeutic cell targets for AAV-based treatment ofLMNAcardiomyopathy. By contrast, careful elucidation of cell-autonomous versus non-cell-autonomous gene functions is essential for the proper design of a gene supplementation therapy for cardiomyopathy.Graphical Abstract
Stress analysis of aluminium die-cast parts including the STL-data of pores
Authors: Gabbert Ulrich , Ringwelski Stefan , Würkner Mathias , Kittsteiner Mario 
Published: July 2023

PurposePores and shrink holes are unavoidable defects in the die-casting mass production process which may significantly influence the strength, fatigue and fracture behaviour as well as the life span of structures, especially if they are subjected to high static and dynamic loads. Such defects should be considered during the design process or after production, where the defects could be detected with the help of computed tomography (CT) measurements. However, this is usually not done in today's mass production environments. This paper deals with the stress analysis of die-cast structural parts with pores found from CT measurements or that are artificially placed within a structure.Design/methodology/approachIn this paper the authors illustrate two general methodologies to take into account the porosity of die-cast components in the stress analysis. The detailed geometry of a die-cast part including all discontinuities such as pores and shrink holes can be included via STL data provided by CT measurements. The first approach is a combination of the finite element method (FEM) and the finite cell method (FCM), which extends the FEM if the real geometry cuts finite elements. The FCM is only applied in regions with pores. This procedure has the advantage that all simulations with different pore distributions, real or artificial, can be calculated without changing the base finite element mesh. The second approach includes the pore information as STL data into the original CAD model and creates a new adapted finite element mesh for the simulation. Both methods are compared and evaluated for an industrial problem.FindingsThe STL data of defects which the authors received from CT measurements could not be directly applied without repairing them. Therefore, for FEM applications an appropriate repair procedure is proposed. The first approach, which combines the FEM with the FCM, the authors have realized within the commercial software tool Abaqus. This combination performs well, which is demonstrated for test examples, and is also applied for a complex industrial project. The developed in-house code still has some limitations which restrict broader application in industry. The second pure FEM-based approach works well without limitations but requires increasing computational effort if many different pore distributions are to be investigated.Originality/valueA new simulation approach which combines the FEM with the FCM has been developed and implemented into the commercial Abaqus FEM software. This approach the authors have applied to simulate a real engineering die-cast structure with pores. This approach could become a preferred way to consider pores in practical applications, where the porosity can be derived either from CT measurements or are artificially adopted for design purposes. The authors have also shown how pores can be considered in the standard FEM analysis as well.
Dynamic association between phonemic awareness and disordered speech recognition moderated by transcription training
Authors: Chen Yu‐Ju , Yeh Lili 
Published: July 2023

AbstractBackgroundPhonetic transcription of disordered speech samples is especially crucial for the assessment and treatment of functional or organic speech‐sound disorders. Previous studies show that students who struggle with the identification and segmentation of speech sounds are more likely to encounter difficulties with clinical phonetic transcription.AimsTo clarify the connection between phonemic awareness and phonetic transcription in Mandarin‐speaking undergraduate students, as well as the improvement of these skills after phonetic transcription training.Methods & ProceduresA pretest–post‐test design was adopted for this study. The experimental group (n = 38) consisted of students majoring in audiology and speech–language pathology who were given 12 weeks of transcription training. The control group (n = 33) consisted of audiology and speech–language pathology majors who completed the same module a year earlier without undergoing the transcription training. Two instruments were used to assess their skills: (1) the Phonemic Awareness Skill Test (PA test) and (2) the Phonetic Transcription Skill Test (PT test) designed for the purposes of the present study.Outcomes & ResultsPerformance on most subtests of the PT and PA tests improved significantly at post‐test for the experiment group, although only PT training was provided. After phonetic transcription training, the relationship between phonemic addition abilities and phonetic transcription strengthened. Phonemic identification was found to be a predictor of undergraduate students’ PT skills of disordered speech samples.Conclusions & ImplicationsResults from this study provide insights into the role of phonetic transcription training in improving phonemic awareness and phonetic transcription skills.What This Paper AddsWhat is already known on the subjectPhonetic transcription of disordered speech samples is especially crucial for the assessment and treatment of functional or organic speech‐sound disorders. Phonemic awareness is not only an essential ability for reading alphabetic language but also associated with acquiring phonetic transcription skills.What this paper adds to existing knowledgeA dynamically changing association between phonemic transcription and phonetic transcription during transcription training was reported. Phonetic transcription training of disordered speech samples acted as a driving force for deeper relationships between the two skills.What are the potential or actual clinical implications of this work?Training phonetic recognition and transcription equips future and practising speech–language pathologists with better skills in managing speech‐sound disorders. Implications for phonemic awareness training also have the potential to extend to the literacy skills of alphabetic language speakers.
Intravenous immunoglobulin and rituximab in a treatment‐refractory COVID‐19‐associated central nervous system vasculitis: A case report and literature review
Authors: Mutlu Onur Anil , İriş Merve , Erener Nursena , Kizilkiliç Osman , Işlak Civan , Seyahi Emire , Saip Sabahattin , Uygunoğlu Uğur 
Published: July 2023

AbstractCentral nervous system (CNS) vasculitis is an uncommon inflammatory disease that affects the brain and spinal cord. It might present with headache, focal neurological deficits, seizures and encephalopathy. CNS vasculitis might be triggered by systemic vasculitides, connective tissue diseases, malignancies and infectious agents, including severe acute respiratory syndrome coronavirus 2. Diagnosis requires a combination of clinical presentation, serological and cerebral spinal fluid analysis, radiological findings (magnetic resonance imaging and conventional angiography), and brain biopsy. In the lack of randomized prospective studies, the treatment approach is based on retrospective cohort studies, anecdotal reports and therapeutic approaches derived from other vasculitides. In this report, we present a case of a 55‐year‐old man who presented with hemiparesthesia 39 days after coronavirus disease 2019 (COVID‐19) infection. During the disease course, the patient developed right‐sided hemiparesis and was referred to our center. Conventional angiogram suggested CNS vasculitis. After an extensive work‐up, systemic vasculitis was excluded. Despite having been treated with pulse steroid and cyclophosphamide, the patient experienced relapses. As we administered intravenous immunoglobulin and rituximab, remission was achieved both in clinical and radiological aspects. In this study, we present the first case of treatment‐refractory CNS vasculitis associated with COVID‐19, which was treated successfully with intravenous immunoglobulin and rituximab. Second, we report a review of COVID‐19‐related CNS vasculitis articles and applied treatment strategies published in English. To elucidate the mechanism of COVID‐19‐related CNS vasculitis, further research is needed.
Ephemeral promises of happiness: Coming out in the Australian accounting profession into the late 2010s
Authors: Egan Matthew , Voss Barbara de Lima 
Published: July 2023

AbstractThis interview‐based study explores how shifting promises of happiness impact on LGBTIQ+ individuals within the workplace. Our study situates within the “Big 4” Australian professional service firms at a time of significant political change, centered around the legislating of marriage equality in 2017. Together with statements of support issued by each of these firms, these moves offered an increasing sense that secure promises of happiness were now offered to “out” LGBTIQ+ staff. A shifting of hetero‐cis normativities was suggested, offering some sense of greater safety, visibility, connection, and acceptance within these workplaces. However, these promises of happiness remained precarious and did little for issues that mattered most (including promotion), particularly individuals of intersectionality, including ethnically diverse and female individuals.
Polynomial ergodicity of an SIRS epidemic model with density‐dependent demographics
Authors: Lan Guijie , Yuan Sanling 
Published: July 2023

AbstractIn this paper, a stochastic susceptible‐infective‐recovered‐susceptible (SIRS) model with density‐dependent demographics is proposed to study the dynamics of transmission of infectious diseases under stochastic environmental fluctuations. We demonstrate that the position of the basic reproduction number with respect to 1 is the threshold between extinction and persistence of the disease under mild extra conditions. That is, under mild extra conditions, when , the disease is eradicated with probability 1; when , the disease is persistent almost surely and the Markov process has a unique stationary distribution and is polynomial ergodic. As an application, we use the 2017 influenza A data from Western Asia to estimate the parameter values of the model and based on that investigate the effect of random noises on the dynamics of the model. Our study reveals that the basic reproduction number is negatively correlated with the noise intensity for the infected but positively correlated with that for the susceptible population, which are different from the findings obtained in the existing literature.
The COPII subunit CsSEC23 mediates fruit glossiness in cucumber
Authors: Gao Luyao , Cao Jiajian , Gong Siyu , Hao Ning , Du Yalin , Wang Chunhua , Wu Tao 
Published: July 2023

SUMMARYTo improve our understanding of the mechanism underlying cucumber glossiness regulation, a novel cucumber mutant with a glossy peel (Csgp) was identified. MutMap, genotyping, and gene editing results demonstrated that CsSEC23, which is the core component of COPII vesicles, mediates the glossiness of cucumber fruit peel. CsSEC23 is functionally conserved and located in the Golgi and endoplasmic reticulum. CsSEC23 could interact with CsSEC31, but this interaction was absent in the Csgp mutant, which decreased the efficiency of COPII vesicle transportation. Genes related to wax and cutin transport were upregulated in the Csgp mutant, and the cuticle structure of the Csgp‐mutant peel became thinner. Moreover, the wax and cutin contents were also changed due to CsSEC23 mutation. Taken together, the results obtained from this study revealed that CsSEC23 mediates cucumber glossiness, and this mediating might be affected by COPII vesicle transportation.
Cross‐talk between zinc and calcium regulates ion transport: A role for the zinc receptor, ZnR/GPR39
Authors: Hershfinkel Michal 
Published: July 2023

AbstractZinc is essential for many physiological functions, with a major role in digestive system, skin health, and learning and memory. On the cellular level, zinc is involved in cell proliferation and cell death. A selective zinc sensing receptor, ZnR/GPR39 is a Gq‐coupled receptor that acts via the inositol trisphosphate pathway to release intracellular Ca2+. The ZnR/GPR39 serves as a mediator between extracellular changes in Zn2+ concentration and cellular Ca2+ signalling. This signalling pathway regulates ion transporters activity and thereby controls the formation of transepithelial gradients or neuronal membrane potential, which play a fundamental role in the physiological function of these tissues. This review focuses on the role of Ca2+ signalling, and specifically ZnR/GPR39, with respect to the regulation of the Na+/H+ exchanger, NHE1, and of the K+/Cl− cotransporters, KCC1‐3, and also describes the physiological implications of this regulation.
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Intestinal microRNAs and bacterial taxa in juvenile mice are associated, modifiable by allochthonous lactobacilli, and affect postnatal maturation
Authors: Taibi Amel , Tokar Tomas , Tremblay Julien , Gargari Giorgio , Streutker Catherine J. , Li Bo , Pierro Agostino , Guglielmetti Simone , Tompkins Thomas A. , Jurisica Igor , Comelli Elena M. 
Published: July 2023

ABSTRACT
The interplay between the intestinal microbiota and host is critical to intestinal ontogeny and homeostasis. MicroRNAs (miRNAs) may be an underlying link. Intestinal miRNAs are microbiota-dependent and, when shed in the lumen, affect resident microorganisms. Yet, longitudinal relationships between intestinal tissue miRNAs, luminal miRNAs, and luminal microorganisms have not been elucidated, especially in early life. Here, we investigated the postnatal cecal miRNA and microbiota populations, their relationship, and their impact on intestinal maturation in specific pathogen-free mice; we also assessed if they can be modified by intervention with allochthonous probiotic lactobacilli. We report that cecal and cecal content miRNA and microbiota signatures are temporally regulated, correlated, and modifiable by probiotics with implications for intestinal maturation. These findings help understand causal relationships within the gut ecosystem and provide a basis for preventing and managing their alterations in diseases throughout life.

IMPORTANCE
The gut microbiota affects intestinal microRNA (miRNA) signatures and is modified by host-derived luminal miRNA. This suggests the existence of close miRNA-microbiota relationships that are critical to intestinal homeostasis. However, an integrative analysis of these relationships and their evolution during intestinal postnatal maturation is lacking. We provide a system-level longitudinal analysis of miRNA-microbiota networks in the intestine of mice at the weaning transition, including tissue and luminal miRNA and luminal microbiota. To address causality and move toward translational applications, we used allochthonous probiotic lactobacilli to modify these longitudinal relationships and showed that they are critical for intestinal maturation in early life. These findings contribute to understand mechanisms that underlie the maturation of the intestinal ecosystem and suggest that interventions aiming at maintaining, or restoring, homeostasis cannot prescind from considering relationships among its components.