bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct activation of PI3K in osteoblasts and osteocytes strengthens murine bone through sex-specific actions on cortical surfaces
Authors: Wee Natalie K Y , McGregor Narelle E , Walker Emma C , Poulton Ingrid J , Dang Michelle Kieu Mi , Gooi Jonathan H , Phillips Wayne A , Sims Natalie A 
Published: July 2024

Abstract
Intracellular phosphoinositide 3-kinase (PI3K) signaling is activated by multiple bone-active receptors. Genetic mutations activating PI3K signaling are associated with clinical syndromes of tissue overgrowth in multiple organs, often including the skeleton. While one formation is increased by removing the PI3K inhibitor (phosphatase and TENsin homolog deleted on chromosome 10 (PTEN)), the effect of direct PI3K activation in the osteoblast lineage has not been reported. We introduced a known gain-of-function mutation in Pik3ca, the gene encoding the p110α catalytic subunit of PI3K, in osteocytes and late osteoblasts using the dentin matrix protein-1 Cre (Dmp1Cre) mouse and assessed the skeletal phenotype. Femur shape was grossly normal, but cortical thickness was significantly greater in both male and female Dmp1Cre.Pik3caH1047R mice, leading to almost doubled bone strength at 12 wk of age. Both sexes had smaller marrow areas from 6 wk of age. Female mice also exhibited greater cross-sectional area, which continued to increase until 24 wk of age, resulting in a further increase in bone strength. Although both male and female mice had increased endocortical mineralizing surface, only female mice had increased periosteal mineralizing surface.
The bone formed in the Dmp1Cre.Pik3caH1047R mice showed no increase in intracortical remodeling nor any defect in cortical bone consolidation. In contrast, on both endocortical and periosteal surfaces, there was more lamellar bone formation, including highly organized osteocyte networks extending along the entire surface at a greater thickness than in control mice. In conclusion, direct activation of PI3Kα in cells targeted by Dmp1Cre leads to high cortical bone mass and strength with abundant lamellar cortical bone in female and male mice with no increase in intracortical remodeling. This differs from the effect of PTEN deletion in the same cells, suggesting that activating PI3Kα in osteoblasts and osteocytes may be a more suitable target to promote formation of lamellar bone.
Deubiquitination of aryl hydrocarbon receptor by USP21 negatively regulates T helper 17 cell differentiation
Authors: Wang Lingbiao , Cheng Hao , Wang Xiaoxia , Zhu Fangming , Tian Na , Xu Zhan , Yin Hanlin , Liang Minrui , Yang Xue , Liu Xinnan , Shan Hongying , Fu Rong , Cao Boran , Li Dan , Xiao Lianbo , Lu Liangjing , Dai Sheng-Ming , Wang Qingwen , Lv Ling , Zou Hejian , Li Bin 
Published: July 2024

Abstract
Aryl hydrocarbon receptor (AhR) is a key transcription factor that modulates the differentiation of T helper 17 (Th17) cells. How AhR is regulated at the post-translational level in Th17 cells remains largely unclear. Here, we identify USP21 as a newly defined deubiquitinase of AhR. We demonstrate that USP21 interacts with and stabilizes AhR by removing the K48-linked polyubiquitin chains from AhR. Interestingly, USP21 inhibits the transcriptional activity of AhR in a deubiquitinating-dependent manner. USP21 deubiquitinates AhR at the K432 residue, and the maintenance of ubiquitination on this site is required for the intact transcriptional activity of AhR. Moreover, the deficiency of USP21 promotes the differentiation of Th17 cells both in vitro and in vivo. Consistently, adoptive transfer of USP21-deficient naïve CD4+ T cells elicits more severe colitis in Rag1−/− recipients. Therefore, our study reveals a novel mechanism in which USP21 deubiquitinates AhR and negatively regulates the differentiation of Th17 cells.
Sporadic neurofibroma of facial nerve presenting as parotid gland tumor: a rare case report
Authors: Hassan Shko H , Salih Karzan M , Salih Abdulwahid M , Qaradakhy Aras J , Abdullah Ari M , Saeed Yadgar A , Muhialdeen Aso S , Habibullah Imad J , Dhahir Hardi M , Kakamad Fahmi H , Ahmed Masty K 
Published: July 2024

Abstract
Intraparotid gland neurofibroma is a rare benign tumor that arises from Schwann cells of the facial nerve within the parotid gland. This case report discusses a 41-year-old woman who experienced a painless preauricular swelling on her right side for over 5 years. Clinical examination and ultrasound revealed a well-defined mass in the parotid gland. The patient underwent total mass excision, resulting in transient facial nerve dysfunction but complete recovery. These tumors often manifest as solitary masses in the parotid region and may compress nearby structures, causing facial paralysis or numbness. Their diagnosis can be challenging due to similarities with other parotid gland tumors and possible associations with neurofibromatosis. Managing intraparotid tumors, including neurofibromas, involves a multidisciplinary approach with input from cytopathologists, radiologists, and surgeons.
The benefits of permutation-based genome-wide association studies
Authors: John Maura , Korte Arthur , Grimm Dominik G 
Published: July 2024

Abstract
Linear mixed models (LMMs) are a commonly used method for genome-wide association studies (GWAS) that aim to detect associations between genetic markers and phenotypic measurements in a population of individuals while accounting for population structure and cryptic relatedness. In a standard GWAS, hundreds of thousands to millions of statistical tests are performed, requiring control for multiple hypothesis testing. Typically, static corrections that penalize the number of tests performed are used to control for the family-wise error rate, which is the probability of making at least one false positive. However, it has been shown that in practice this threshold is too conservative for normally distributed phenotypes and not stringent enough for non-normally distributed phenotypes. Therefore, permutation-based LMM approaches have recently been proposed to provide a more realistic threshold that takes phenotypic distributions into account. In this work, we discuss the advantages of permutation-based GWAS approaches, including new simulations and results from a re-analysis of all publicly available Arabidopsis phenotypes from the AraPheno database.
Survey of extended main-sequence turn-offs in galactic open clusters: stellar rotations from Gaia RVS spectra
Authors: Cordoni G , Casagrande L , Yu J , Milone A P , Marino A F , D’Antona F , Dell’Agli F , Buder S , Tailo M 
Published: July 2024

ABSTRACT
The origin of extended main-sequence turn-offs (eMSTO) in star clusters younger than 2 Gyr still challenges our current understanding of stellar evolution. Exploiting data from Gaia Data Release 3 (DR3), we investigate eMSTOs in a large sample of 32 Galactic open clusters younger than 2.4 Gyr. We first validate Gaia rotational velocities from radial velocity spectrometer spectra by comparing them with literature values and assessing their correlation with magnetic activity measurements from LAMOST spectra. We detect a general positive correlation between turn-off colour and projected stellar rotation, with slow-rotating stars predominantly found on the bluer side of the turn-off. Comparing our observations with theoretical models, we find that the eMSTO morphology is well reproduced by a single population formed with a high rotation rate, and observed with rotation axis inclination ranging between 0° (pole-on) and 90° (edge-on). This contrasts with observations of Magellanic Cloud clusters, where a population of non-rotating stars appears to be ubiquitous in clusters younger than 700 Myr. However, we note that our interpretation, while successfully explaining the overall eMSTO morphology, cannot fully explain the observed projected rotational velocities. Additionally, two young clusters, NGC 3532 and NGC 2287, exhibit moderate evidence of a split-main sequence in colour and rotation, suggesting a possible small spread in the initial rotation rate. Finally, we advise caution in determining the ages of young clusters from non-rotating isochrones, as neglecting the effects of stellar rotation can impact the isochrone dating by up to factors of 5–20 per cent.
Structure and RNA-binding of the helically extended Roquin CCCH-type zinc finger
Authors: Tants Jan-Niklas , Oberstrass Lasse , Weigand Julia E , Schlundt Andreas 
Published: July 2024

Abstract
Zinc finger (ZnF) domains appear in a pool of structural contexts and despite their small size achieve varying target specificities, covering single-stranded and double-stranded DNA and RNA as well as proteins. Combined with other RNA-binding domains, ZnFs enhance affinity and specificity of RNA-binding proteins (RBPs). The ZnF-containing immunoregulatory RBP Roquin initiates mRNA decay, thereby controlling the adaptive immune system. Its unique ROQ domain shape-specifically recognizes stem-looped cis-elements in mRNA 3′-untranslated regions (UTR). The N-terminus of Roquin contains a RING domain for protein-protein interactions and a ZnF, which was suggested to play an essential role in RNA decay by Roquin. The ZnF domain boundaries, its RNA motif preference and its interplay with the ROQ domain have remained elusive, also driven by the lack of high-resolution data of the challenging protein. We provide the solution structure of the Roquin-1 ZnF and use an RBNS-NMR pipeline to show that the ZnF recognizes AU-rich RNAs. We systematically refine the contributions of adenines in a poly(U)-background to specific complex formation. With the simultaneous binding of ROQ and ZnF to a natural target transcript of Roquin, our study for the first time suggests how Roquin integrates RNA shape and sequence features through the ROQ-ZnF tandem.
Distinct mobility patterns of BRCA2 molecules at DNA damage sites
Authors: Paul Maarten W , Aaron Jesse , Wait Eric , Van Genderen Romano M , Tyagi Arti , Kabbech Hélène , Smal Ihor , Chew Teng-Leong , Kanaar Roland , Wyman Claire 
Published: July 2024

Abstract
BRCA2 is an essential tumor suppressor protein involved in promoting faithful repair of DNA lesions. The activity of BRCA2 needs to be tuned precisely to be active when and where it is needed. Here, we quantified the spatio-temporal dynamics of BRCA2 in living cells using aberration-corrected multifocal microscopy (acMFM). Using multicolor imaging to identify DNA damage sites, we were able to quantify its dynamic motion patterns in the nucleus and at DNA damage sites. While a large fraction of BRCA2 molecules localized near DNA damage sites appear immobile, an additional fraction of molecules exhibits subdiffusive motion, providing a potential mechanism to retain an increased number of molecules at DNA lesions. Super-resolution microscopy revealed inhomogeneous localization of BRCA2 relative to other DNA repair factors at sites of DNA damage. This suggests the presence of multiple nanoscale compartments in the chromatin surrounding the DNA lesion, which could play an important role in the contribution of BRCA2 to the regulation of the repair process.
Sequence diversity of apidaecin-like peptides arresting the terminating ribosome
Authors: Huang Weiping , Baliga Chetana , Vázquez-Laslop Nora , Mankin Alexander S 
Published: July 2024

Abstract
The Proline-rich Antimicrobial Peptide (PrAMP) apidaecin (Api) inhibits translation by binding in the ribosomal nascent peptide exit tunnel, trapping release factors RF1 or RF2, and arresting ribosomes at stop codons. To explore the extent of sequence variations of the native 18-amino acid Api that allows it to preserve its activity, we screened a library of synthetic mutant Api genes expressed in bacterial cells, resulting in nearly 350000 peptide variants with multiple substitutions. By applying orthogonal negative and positive selection strategies, we identified a number of multi-substituted Api variants capable of arresting ribosomes at stop codons. Our findings underscore the critical contribution of specific amino acid residues of the peptide for its on-target function while significantly expanding the variety of PrAMPs acting on the terminating ribosome. Additionally, some of the tested synthesized multi-substituted Api variants exhibit improved antibacterial activity compared to that of the wild type PrAMP and may constitute the starting point to develop clinically useful antimicrobials.
End resection and telomere healing of DNA double-strand breaks during nematode programmed DNA elimination
Authors: Estrem Brandon , Davis Richard E , Wang Jianbin 
Published: July 2024

Abstract
Most DNA double-strand breaks (DSBs) are harmful to genome integrity. However, some forms of DSBs are essential to biological processes, such as meiotic recombination and V(D)J recombination. DSBs are also required for programmed DNA elimination (PDE) in ciliates and nematodes. In nematodes, the DSBs are healed with telomere addition. While telomere addition sites have been well characterized, little is known regarding the DSBs that fragment nematode chromosomes. Here, we used embryos from the human and pig parasitic nematode Ascaris to characterize the DSBs. Using END-seq, we demonstrate that DSBs are introduced before mitosis, followed by extensive end resection. The resection profile is unique for each break site, and the resection generates 3′-overhangs before the addition of neotelomeres. Interestingly, telomere healing occurs much more frequently on retained DSB ends than on eliminated ends. This biased repair of the DSB ends may be due to the sequestration of the eliminated DNA into micronuclei, preventing neotelomere formation at their ends. Additional DNA breaks occur within the eliminated DNA in both Ascaris and Parascaris, ensuring chromosomal breakage and providing a fail-safe mechanism for PDE. Overall, our data indicate that telomere healing of DSBs is specific to the break sites responsible for nematode PDE.
Two pyridoxal phosphate homeostasis proteins are essential for management of the coenzyme pyridoxal 5′-phosphate in Arabidopsis
Authors: Farkas Peter , Fitzpatrick Teresa B 
Published: July 2024

Abstract
Coenzyme management is important for homeostasis of the pool of active metabolic enzymes. The coenzyme pyridoxal 5′-phosphate (PLP) is involved in diverse enzyme reactions including amino acid and hormone metabolism. Regulatory proteins that contribute to PLP homeostasis remain to be explored in plants. Here, we demonstrate the importance of proteins annotated as PLP homeostasis proteins (PLPHPs) for controlling PLP in Arabidopsis (Arabidopsis thaliana). A systematic analysis indicates that while most organisms across kingdoms have a single PLPHP homolog, Angiosperms have two. PLPHPs from Arabidopsis bind PLP and exist as monomers, in contrast to reported PLP-dependent enzymes, which exist as multimers. Disrupting the function of both PLPHP homologs perturbs vitamin B6 (pyridoxine) content, inducing a PLP deficit accompanied by light hypersensitive root growth, unlike PLP biosynthesis mutants. Micrografting studies show that the PLP deficit can be relieved distally between shoots and roots. Chemical treatments probing PLP-dependent reactions, notably those for auxin and ethylene, provide evidence that PLPHPs function in the dynamic management of PLP. Assays in vitro show that Arabidopsis PLPHP can coordinate PLP transfer and withdrawal from other enzymes. This study thus expands our knowledge of vitamin B6 biology and highlights the importance of PLP coenzyme homeostasis in plants.
Development of Movement and Postural Patterns in Full-Term Infants Who Are at Low Risk in Belgium, India, Norway, and the United States
Authors: Boswell Lynn , Adde Lars , Fjørtoft Toril , Pascal Aurelie , Russow Annemarie , Støen Ragnhild , Thomas Niranjan , Van den Broeck Christine , de Regnier Raye-Ann 
Published: July 2024

Abstract

Objective
The objective of this study was to investigate the influences on motor development in infants who are at low risk from Belgium, India, Norway, and the United States using the General Movement Assessment at 10–16 weeks postterm age.

Methods
This was a cross-sectional study of prospectively enrolled full-term infants at low risk (n = 186). Certified General Movement Assessment observers rated the fidgety movements, quality of the movement patterns, age-adequacy of the movement repertoire, postural patterns, movement character, and overall Motor Optimality Score–Revised (MOS-R). Scores were evaluated for associations with sex, birth weight category, gestational age, postterm age at video, and country.

Results
The majority of infants had normal fidgety movements (179/186, 96.2%). This did not vary by sex, birth weight, gestational age, postterm age at video, or country. All infants showed normal&gt;atypical movement patterns. Variability was seen for age adequacy (optimal: 137/183, 74.9%), postural patterns (normal&gt;atypical: 164/183, 89.6%), and smooth/ fluent movement character (138/183, 75.4%). Gestational age and postterm age at video were associated with atypical postural patterns, but in multivariable regression, only younger postterm age retained significance (OR = 2.94, 95% CI = 1.05–8.24). Lack of age adequacy was associated with postterm age (OR = 13.15, 95% CI = 4.36–39.72) and country (compared with Norway; Belgium OR = 3.38 95% CI = 12.4–9.22; India OR = 3.16, 95% CI = 1.01–9.87; United States not significant). Infants from India also showed lower rates of an optimal MOS-R (25–28) than infants from Norway.

Conclusion
The normality and temporal organization of fidgety movements did not differ by sex, birth weight, postterm age, or country, suggesting that the fidgety movements are free of cultural and environmental influences. The majority of full-term infants who were healthy in this cohort showed normal scores for all aspects of motor development tested using the MOS-R. Differences in age adequacy and MOS-R by country warrant investigation with larger cohorts and longitudinal follow-up.

Impact
Understanding variations in typical motor development is essential to interpreting patterns of movement and posture in infants at risk for atypical development. Using the framework of Prechtl’s General Movement Assessment, this study showed that the development of movement and posture in healthy infants was affected by age and country of birth, but the development of the fidgety movements appeared to be free of these influences. Local norms may be needed to interpret the Motor Optimality Score-Revised in all populations, but further research on this topic is needed.
Homotopy Theoretic Properties Of Open Books
Authors: Huang Ruizhi , Theriault Stephen 
Published: July 2024

ABSTRACT
We study the homotopy groups of open books in terms of those of their pages and bindings. Under homotopy theoretic conditions on the monodromy we prove an integral decomposition result for the based loop space on an open book, and under more relaxed conditions we prove a rational loop space decomposition. The latter case allows for a rational dichotomy theorem for open books, as an extension of the classical dichotomy in rational homotopy theory. As a direct application, we show that for Milnor’s open book decomposition of an odd sphere with monodromy of finite order the induced action of the monodromy on the homology groups of its page cannot be nilpotent.
Behavioral Engagement and Activation Model Study (BEAMS): A latent class analysis of adopters and non-adopters of digital health technologies among people with Type 2 diabetes
Authors: Piette John D , Lee Keni C S , Bosworth Hayden B , Isaacs Diana , Cerrada Christian J , Kainkaryam Raghu , Liska Jan , Lee Felix , Kennedy Adee , Kerr David 
Published: July 2024

Abstract
Many people with Type 2 diabetes (T2D) who could benefit from digital health technologies (DHTs) are either not using DHTs or do use them, but not for long enough to reach their behavioral or metabolic goals. We aimed to identify subgroups within DHT adopters and non-adopters and describe their unique profiles to better understand the type of tailored support needed to promote effective and sustained DHT use across a diverse T2D population. We conducted latent class analysis of a sample of adults with T2D who responded to an internet survey between December 2021 and March 2022. We describe the clinical and psychological characteristics of DHT adopters and non-adopters, and their attitudes toward DHTs. A total of 633 individuals were characterized as either DHT “Adopters” (n = 376 reporting any use of DHT) or “Non-Adopters” (n = 257 reporting never using any DHT). Within Adopters, three subgroups were identified: 21% (79/376) were “Self-managing Adopters,” who reported high health activation and self-efficacy for diabetes management, 42% (158/376) were “Activated Adopters with dropout risk,” and 37% (139/376) were “Non-Activated Adopters with dropout risk.” The latter two subgroups reported barriers to using DHTs and lower rates of intended future use. Within Non-Adopters, two subgroups were identified: 31% (79/257) were “Activated Non-Adopters,” and 69% (178/257) were “Non-Adopters with barriers,” and were similarly distinguished by health activation and barriers to using DHTs. Beyond demographic characteristics, psychological, and clinical factors may help identify different subgroups of Adopters and Non-Adopters.
Benefits of using both the Hunger Vital Sign and brief nutrition security screener in health-related social needs screening
Authors: Calloway Eric E , Coakley Kathryn E , Carpenter Leah R , Gargano Tony , Yaroch Amy L 
Published: July 2024

Abstract
Food security is a commonly screened for health-related social need at hospitals and community settings, and until recently, there were no tools to additionally screen for nutrition security. The purpose of this study was to assess the potential advantage of including a one-item brief nutrition security screener (BNSS) alongside the commonly used two-item Hunger Vital Sign (HVS) food security screener for identifying individuals with diet-related health risks. Cross-sectional survey data were collected from April to June 2021. Generalized linear mixed models were used to assess associations between screening status and dietary and health variables. Recruitment was done across five states (California, Florida, Maryland, North Carolina, and Washington) from community-based organizations. Participants (n = 435) were, on average, 44.7 years old (SD = 14.5), predominantly women (77%), and racially/ethnically diverse. In adjusted analyses, being in the food insecure and nutrition insecure group (but not the food insecure and nutrition secure or food secure and nutrition insecure groups) was associated with significantly increased odds for self-reported “fair” or “poor” general health [OR = 2.914 (95% CI = 1.521–5.581)], reporting at least one chronic condition [2.028 (1.024–4.018)], and “low” fruit and vegetable intake [2.421 (1.258–4.660)], compared with the food secure and nutrition secure group. These findings support using both the HVS and BNSS simultaneously in health-related social needs screening to identify participants at the highest risk for poor dietary and health outcomes and warrant further investigation into applying these screeners to clinical and community settings.