bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gender differences in the distribution of children’s physical activity: evidence from nine countries
Authors: Kretschmer Luke , Salali Gul Deniz , Andersen Lars Bo , Hallal Pedro C , Northstone Kate , Sardinha Luís B. , Dyble Mark , Bann David ,   International Children’s Accelerometry Database (ICAD) Collaborators
Published: April 2023

BackgroundPhysical activity in childhood is thought to influences health and development. Previous studies have found that boys are typically more active than girls, yet the focus has largely been on differences in average levels or proportions above a threshold rather than the full distribution of activity across all intensities. We thus examined differences in the distribution of physical activity between girls and boys in a multi-national sample of children.MethodsWe used the harmonised International Children Accelerometery Database (ICAD), including waist-worn accelerometery data from 15,461 individuals (Boys: 48.3%) from 9 countries. Employing Generalised Additive Models of Location, Shape, and Scale (GAMLSS) we investigated gender differences in the distribution of individuals, including comparisons of variability (SD) and average physical activity levels (mean and median) and skewness. We conducted this analysis for each activity intensity (Sedentary, Light, and Moderate-to-Vigorous (MVPA)) and a summary measure (counts per minute (CPM)).ResultsSizable gender differences in the distribution of activity were found for moderate to vigorous activity and counts per minute, with boys having higher average levels (38% higher mean volumes of MVPA, 20% higher CPM), yet substantially more between-person variability (30% higher standard deviation (SD) for MVPA, 17% higher SD for CPM); boys’ distributions were less positively skewed than girls. Conversely, there was little to no difference between girls and boys in the distribution of sedentary or light-intensity activity.ConclusionsInequality in activity between girls and boys was driven by MVPA. The higher mean volumes of MVPA in boys occurred alongside greater variability. This suggests a need to consider the underlying distribution of activity in future research; for example, interventions which target gender inequality in MVPA may inadvertently lead to increased inequality within girls.
Disrupted-in-schizophrenia 1 (DISC1) protein aggregates in cerebrospinal fluid are elevated in first-episode psychosis patients
Authors: Pils Marlene , Rutsch Julia , Eren Feride , Engberg Göran , Piehl Fredrik , Cervenka Simon , Sellgren Carl , Troßbach Svenja , Willbold Dieter , Erhardt Sophie , Bannach Oliver , Korth Carsten 
Published: April 2023

AbstractThe Disrupted-in-schizophrenia 1 (DISC1) protein is a key regulator at the intersection of signaling pathways relevant for adaptive behavior. It is prone to posttranslational changes such as misassembly and aggregation but the significance of such transformations for human mental illness has remained unclear.Here we demonstrate that DISC1 protein aggregates are increased in CSF samples of patients with first episode psychosis (n=50) compared to healthy controls (n=47), as measured by the highly sensitive surface-based fluorescence intensity distribution analysis technology that enables single aggregate detection. The concentration was in the low femtomolar range. No correlations were found to symptom levels, but the difference was particularly significant in the subset of patients receiving the diagnoses “schizophrenia, unspecified” (DSM IV 295.9) or schizoaffective disorder (DSM IV 295.70) at 18-month follow-up.The occurrence of protein aggregatesin vivoin patients with psychotic disorders has not been previously reported. It underscores the significance of posttranslational modifications of proteins both as pathogenetic mechanisms and as potential diagnostic markers in these disorders.
Sentence superiority in the reading brain
Authors: Dufau Stéphane , Yeaton Jeremy , Badier Jean-Michel , Chen Sophie , Holcomb Phillip J. , Grainger Jonathan 
Published: April 2023

ABSTRACTWhen a sequence of written words is briefly presented and participants are asked to identify just one word at a post-cued location, then word identification accuracy is higher when the word is presented in a grammatically correct sequence compared with an ungrammatical sequence. This sentence superiority effect has been reported in several behavioral studies and two EEG investigations. Taken together, the results of these studies support the hypothesis that the sentence superiority effect is primarily driven by rapid access to a sentence-level representation via partial word identification processes that operate in parallel over several words. Here we used MEG to examine the neural structures involved in this early stage of written sentence processing, and to further specify the timing of the different processes involved. Source activities over time showed grammatical vs. ungrammatical differences first in the left inferior frontal gyrus (IFG: 325-400 ms), then the left anterior temporal lobe (ATL: 475-525 ms), and finally in both left IFG and left posterior superior temporal gyrus (pSTG: 550-600 ms). We interpret the early IFG activity as reflecting the rapid bottom-up activation of sentence-level representations, including syntax, enabled by partly parallel word processing. Subsequent activity in ATL and pSTG is thought to reflect the constraints imposed by such sentence-level representations on on-going word-based semantic activation (ATL), and the subsequent development of a more detailed sentence-level representation (pSTG). These results provide further support for a cascaded interactive-activation account of sentence reading.
Ca2+/Calmodulin Dependent Protein Kinase Kinase-2 (CaMKK2) promotes Protein Kinase G (PKG)-dependent actin cytoskeletal assembly to increase tumor metastasis
Authors: Mukherjee Debarati , Previs Rebecca A , Haines Corinne N , Abo Muthana Al , Juras Patrick K , Strickland Kyle C , Chakraborty Binita , Artham Sandeep , Whitaker Regina , Hebert Katherine L , Fontenot Jake , Patierno Steven R , Freedman Jennifer A , Lau Frank H , Burow Matthew , Chang Ching-Yi , McDonnell Donald P. 
Published: April 2023

AbstractTriple-negative breast cancers (TNBCs) tend to become highly invasive early during cancer development. Despite some successes in the initial treatment of patients diagnosed with early-stage localized TNBC, the rate of metastatic recurrence remains high with poor long-term survival outcomes. Here we show that elevated expression of the serine/threonine-kinase, Calcium/Calmodulin (CaM)-dependent protein kinase kinase-2 (CaMKK2), is highly correlated with tumor invasiveness. We determined that genetic disruption of CaMKK2 expression, or inhibition of its activity, disrupted spontaneous metastatic outgrowth from primary tumors in murine xenograft models of TNBC. High-grade serous ovarian cancer (HGSOC), a high-risk, poor-prognosis ovarian cancer subtype, shares many genetic features with TNBC, and importantly, CaMKK2 inhibition effectively blocked metastatic progression in a validated xenograft model of this disease. Probing the mechanistic links between CaMKK2 and metastasis we defined the elements of a new signaling pathway that impacts actin cytoskeletal dynamics in a manner which increases cell migration/invasion and metastasis. Notably, CaMKK2 increases the expression of the phosphodiesterase PDE1A which decreases the cGMP-dependent activity of protein kinase G1 (PKG1). This inhibition of PKG1 results in decreased phosphorylation of Vasodilator-Stimulated Phosphoprotein (VASP), which in its hypophosphorylated state binds to and regulates F-actin assembly to facilitate contraction/cell movement. Together, these data establish a targetable CaMKK2-PDE1A-PKG1-VASP signaling pathway that controls cancer cell motility and metastasis. Further, it credentials CaMKK2 as a therapeutic target that can be exploited in the discovery of agents for use in the neoadjuvant/adjuvant setting to restrict tumor invasiveness in patients diagnosed with early-stage TNBC or localized HGSOC.
Poor biosafety and biosecurity practices and haphazard antibiotics usage in poultry farms in Nepal hindering antimicrobial stewardship
Authors: Poudel Ajit , Sharma Shreeya , Dhital Kavya , Bhandari Shova , Napit Rajindra , Puri Dhiraj , Karmacharya Dibesh B. 
Published: April 2023

AbstractPoultry industry in Nepal has experienced remarkable growth in the last decade, but farm biosafety and biosecurity measures are often overlooked by farmers due to lack of knowledge or to save cost. As a result, farms often suffer from sporadic and regular outbreaks of many zoonotic diseases such as highly pathogenic avian influenza (HPAI), impacting production and creating public health challenges. Poor farm management practices, including overuse of antibiotics for prophylaxis and therapeutics, can complicate the spread of poultry diseases by creating and enhancing antimicrobial resistance (AMR) that is threating to both, poultry, and human health.We assessed biosafety, biosecurity risks and AMR stewardship in sixteen poultry farms located in four districts (Ramechhap, Nuwakot, Sindhupalchowk, and Kavre) surrounding densely populated Kathmandu valley. Risk assessment and AMR stewardship evaluation questionnaire were administered to formulate biosafety and biosecurity compliance matrix (BBCM). Risk assessment checklist assessed facility operations, personnel and standard operating procedures, water supply, cleaning and maintenance, rodent/pest control and farm record keeping. Oral and cloacal samples from the poultry were collected, pooled, and screened for eight poultry pathogens using Polymerase Chain Reaction (PCR) tests.Based on BBCM, we identified one of the farms in Sindhupalchowk (Farm 4) having the most (BBCM score= 67%) and a farm in Kavre (Farm 3) to having the least (BBCM score= 12%) biosafety and biosecurity compliance. Although most of the farms (61.6%) followed general poultry farming practices, only half had clean and well-maintained farms. Personal safety standard procedure compliance (BBCM score = 42.4%) and rodent control (BBCM score = 3.1%) were the biggest gaps. At least one of either bacterial or viral pathogen was detected in all farms.Mycoplasma gallisepticumwas the most common disease detected in all but one farm, followed byMycoplasma synoviae. Although more than half of the farmers considered AMR a threat, over 26% of them used antibiotics as a preventive measure and 81% did not consider withdrawal period for antibiotics prior to processing of their meat products. Additionally, antibiotics classified as Watch and Restrict by the WHO were frequently used by the farmers to treat bacterial infections in their farms. Lack of awareness and inadequate enforcement of regulations have exacerbated the risk of disease transmission in farms and compromised antimicrobial stewardship.
Stray cats and dogs carrying zoonoticEnterocytozoon bieneusigenotype D in China: a public health concern
Authors: Zhang Yidan , Zhang Yan , Mi Rongsheng , Xia Luming , Han Hongxiao , Ma Tao , Gong Haiyan , Huang Yan , Han Xiangan , Chen Zhaoguo 
Published: April 2023

AbstractEnterocytozoon bieneusiis reported to be a common microsporidian of humans and animals in various countries. However, scarce information onE. bieneusihas been recorded in cats (Felis catus) and dogs (Canis familiaris) in China. As such, we undertook molecular epidemiological investigation ofE. bieneusiin cats and dogs in Shanghai, China. A total of 359 genomic DNAs were extracted from individual faecal samples from cats (n= 59) and dogs (n= 300), and then tested using a nested PCR-based sequencing approach employing internal transcribed spacer (ITS) of nuclear ribosomal DNA as the genetic marker.Enterocytozoon bieneusiwas detected in 34 of all 359 (9.5%) faecal samples from cats (32.2%; 19/59) and dogs (5.0%; 15/300), including 24 stray cats and dogs (22.6%; 24/106), as well as ten household/raised cats and dogs (4.0%; 10/253). Correlation analyses revealed thatE. bieneusipositive rates were significantly associated with stray cats and dogs (P< 0.05). The analysis of ITS sequence data revealed the presentation of five known genotypes CD7, CHN-HD2, D, PtEb IX and Type IV and two novel genotypes D-like1 and PtEb IX-like1. Zoonotic genotype D was the predominant type with percentage of 61.8 (21/34). Phylogenetic analysis of ITS sequence data sets showed that genotypes D, D-like1 and Type IV clustered within Group 1, showing zoonotic potential. The others were assigned into Group 10 with host specificity. These findings suggested that cats and dogs in Shanghai harbor zoonotic genotype D ofE. bieneusiand may have a significant risk for zoonotic transmission. Further insight into the epidemiology ofE. bieneusiin animals, water and the environment from other areas in China will be important to have an informed position on the public health significance of microsporidiosis caused by this microbe.
Proteomic Investigation of Neural Stem Cell to Oligodendrocyte Precursor Cell Differentiation Reveals Phosphorylation-Dependent Dclk1 Processing
Authors: Hardt Robert , Dehghani Alireza , Schoor Carmen , Gödderz Markus , Cengiz Winter Nur , Ahmadi Shiva , Sharma Ramesh , Schork Karin , Eisenacher Martin , Gieselmann Volkmar , Winter Dominic 
Published: April 2023

SummaryOligodendrocytes are generated via a two-step mechanism from pluripotent neural stem cells (NSCs): after differentiation of NSCs to oligodendrocyte precursor/NG2 cells (OPCs), they further develop into mature oligodendrocytes. The first step of this differentiation process is only incompletely understood. In this study, we utilized the neurosphere assay to investigate NSC to OPC differentiation in a time course-dependent manner by mass spectrometry-based (phospho-) proteomics. We identify double cortin like kinase 1 (Dclk1) as one of the most prominently regulated proteins in both datasets, and show that it undergoes a gradual transition between its short/long isoform during NSC to OPC differentiation. This is regulated by phosphorylation of its SP-rich region, resulting in inhibition of proteolytic Dclk1 long cleavage, and therefore Dclk1 short generation. Through interactome analyses of different Dclk1 isoforms by proximity biotinylation, we characterize their individual putative interaction partners and substrates.
Structure-function Analyses Reveal Key Molecular Determinants of HIV-1 CRF01_AE Resistance to the Entry Inhibitor Temsavir
Authors: Prévost Jérémie , Chen Yaozong , Zhou Fei , Tolbert William D. , Gasser Romain , Medjahed Halima , Gottumukkala Suneetha , Hessell Ann J. , Rao Venigalla B. , Pozharski Edwin , Huang Rick K. , Matthies Doreen , Finzi Andrés , Pazgier Marzena 
Published: April 2023

SummaryThe HIV-1 entry inhibitor temsavir prevents CD4 from interacting with the envelope glycoprotein (Env) and blocks its conformational changes. To do this temsavir relies on the presence of a residue with small side chain at position 375 in Env and is unable to neutralize viral strains like CRF01_AE carrying His375. Here we investigate the mechanism of temsavir-resistance and show that residue 375 is not the sole determinant of resistance. At least six additional residues within the gp120 inner domain layers, including five distant from the drug-binding pocket, contribute to resistance. A detailed structure-function analysis using engineered viruses and soluble trimer variants reveal that the molecular basis of resistance is mediated by crosstalk between His375 and the inner domain layers. Furthermore, our data confirm that temsavir can adjust its binding mode to accommodate changes in Env conformation, a property that likely contributes to its broad-antiviral activity.
VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis
Authors: Rizvi Fatima , Lee Yu-Ri , Diaz-Aragon Ricardo , So Juhoon , Florentino Rodrigo M. , Smith Anna R. , Everton Elissa , Ostrowska Alina , Jung Kyounghwa , Tam Ying , Muramatsu Hiromi , Pardi Norbert , Weissman Drew , Soto-Gutierrez Alejandro , Shin Donghun , Gouon-Evans Valerie 
Published: April 2023

SummaryThe liver is known for its remarkable regenerative ability through proliferation of hepatocytes. Yet, during chronic injury or severe hepatocyte death, proliferation of hepatocytes is exhausted. To overcome this hurdle, we propose vascular-endothelial-growth-factor A (VEGFA) as a therapeutic means to accelerate biliary epithelial cell (BEC)-to-hepatocyte conversion. Investigation in zebrafish establishes that blocking VEGF receptors abrogates BEC-driven liver repair, while VEGFA overexpression promotes it. Delivery of VEGFA via non-integrative and safe nucleoside-modified mRNA encapsulated into lipid-nanoparticles (mRNA-LNP) in acutely or chronically injured mouse livers induces robust BEC-to-hepatocyte conversion and reversion of steatosis and fibrosis. In human and murine diseased livers, we further identified VEGFA-receptor KDR-expressing BECs associated with KDR-expressing cell-derived hepatocytes. This defines KDR-expressing cells, most likely being BECs, as facultative progenitors. This study reveals novel therapeutic benefits of VEGFA delivered via nucleoside-modified mRNA-LNP, whose safety is widely validated with COVID-19 vaccines, for harnessing BEC-driven repair to potentially treat liver diseases.Graphical AbstractHighlightsComplementary mouse and zebrafish models of liver injury demonstrate the therapeutic impact of VEGFA-KDR axis activation to harness BEC-driven liver regeneration.VEGFA mRNA LNPs restore two key features of the chronic liver disease in humans such as steatosis and fibrosis.Identification in human cirrhotic ESLD livers of KDR-expressing BECs adjacent to clusters of KDR+ hepatocytes suggesting their BEC origin.KDR-expressing BECs may represent facultative adult progenitor cells, a unique BEC population that has yet been uncovered.
Bitesize bundles F-actin and influences actin remodeling in syncytialDrosophilaembryo development
Authors: Yeh Anna R. , Hoeprich Gregory J. , Goode Bruce L. , Martin Adam C. 
Published: April 2023

AbstractActin networks undergo rearrangements that influence cell and tissue shape. Actin network assembly and organization is regulated in space and time by a host of actin binding proteins. TheDrosophilaSynaptotagmin-like protein, Bitesize (Btsz), is known to organize actin at epithelial cell apical junctions in a manner that depends on its interaction with the actin-binding protein, Moesin. Here, we showed that Btsz functions in actin reorganization at earlier, syncytial stages ofDrosophilaembryo development. Btsz was required for the formation of stable metaphase pseudocleavage furrows that prevented spindle collisions and nuclear fallout prior to cellularization. While previous studies focused on Btsz isoforms containing the Moesin Binding Domain (MBD), we found that isoforms lacking the MBD also function in actin remodeling. Consistent with this, we found that the C-terminal half of BtszB cooperatively binds to and bundles F-actin, suggesting a direct mechanism for Synaptotagmin-like proteins regulating actin organization during animal development.
Serum from pregnant donors induces human beta cell proliferation and insulin secretion
Authors: Sylvester-Armstrong Kendra R. , Reeder Callie F. , Powell Andrece , Becker Matthew W. , Hagan D. Walker , Chen Jing , Mathews Clayton E. , Wasserfall Clive H. , Atkinson Mark A. , Egerman Robert , Phelps Edward A. 
Published: April 2023

ABSTRACTPancreatic beta cells are among the slowest replicating cells in the human body. Human beta cells usually do not increase in number with exceptions being during the neonatal period, in cases of obesity, and during pregnancy. This project explored maternal serum for stimulatory potential on human beta cell proliferation and insulin output. Gravid, full-term women who were scheduled to undergo cesarean delivery were recruited for this study. A human beta cell line was cultured in media supplemented with serum from pregnant and non-pregnant donors and assessed for differences in proliferation and insulin secretion. A subset of pregnant donor sera induced significant increases in beta cell proliferation and insulin secretion. Pooled serum from pregnant donors also increased proliferation in primary human beta cells but not primary human hepatocytes indicating a cell-type specific effect. This study suggests stimulatory factors in human serum during pregnancy could provide a novel approach for human beta cell expansion.
Political hegemony and accounting discourse: valuing nationalization
Authors: Pujiningsih Sri , Suryani Ani Wilujeng , Larasati Ika Putri , Yusuf Sharifah Norzehan Syed 
Published: April 2023

PurposeThis study aims to discover the role of accounting and media in hegemonic discourse for divestment valuation of PT Freeport Indonesia shares.Design/methodology/approachThis study employs data from 608 news articles from 5 national media. This study uses Gramsci's concept of hegemony and Laclau and Mouffe's hegemonic discourse to explore the ideological role of accounting in the formation of historical blocs and investigate the contestants' discursive strategies through the chains of equivalence and difference.FindingsThe incumbent presidential candidate, by involving political and intellectual actors, has succeeded in taking over and shifting PT Freeport Indonesia's hegemony to maintain its power, through the ideology of divestment and accounting. The media played a role in the victory of the pro-divestment bloc in the hegemonic divestment discourse contest. The pro-divestment bloc's discursive strategy uses more formal and technical language styles than the anti-divestment bloc, which uses informal language styles. The pro-divestment bloc uses the key signifiers of low price, improved financial performance, nationalization and welfare, as opposed to the anti-divestment bloc, with the key signifiers of high price, declining financial performance and neoliberalist colonization.Practical implicationsThe implications of this research may encourage accounting academics to contribute to emancipatory social movements in the struggle for hegemony. The implication for policy makers is the importance of involving the public, intellectual actors, political actors and the media in supporting diverse state strategic policies in the national interest.Originality/valueThis paper contributes to Gramsci's theory of hegemony and Laclau and Mouffe's hegemonic discourse to understand the role of accounting and media in a nationalization project as an emancipatory social movement, as well as a hegemonic shifting political movement.