bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nutritional vitamin B12 regulates RAS/MAPK-mediated cell fate decisions through the one-carbon metabolism
Authors: Laranjeira Ana Cristina , Berger Simon , Kohlbrenner Tea , Greter Nadja R. , Hajnal Alex 
Published: October 2023

AbstractVitamin B12 is an essential nutritional co-factor for the folate and methionine cycles, which together constitute the one-carbon metabolism. Here, we show that dietary uptake of vitamin B12 modulates cell fate decisions controlled by the conserved RAS/MAPK signaling pathway inC. elegans. A bacterial diet rich in vitamin B12 increases vulval induction, germ cell apoptosis and oocyte differentiation. These effects are mediated by different one-carbon metabolites in a tissue-specific manner. Vitamin B12 enhances via the choline/phosphatidylcholine metabolism vulval induction by down-regulating fat biosynthesis genes and increasing H3K4 tri-methylation, which results in increased expression of RAS/MAPK target genes. Furthermore, the nucleotide metabolism and H3K4 tri-methylation positively regulate germ cell apoptosis and oocyte production. Using mammalian cells carrying different activated KRAS and BRAF alleles, we show that the effects of methionine on RAS/MAPK-regulated phenotype are conserved in mammals. Our findings suggest that the vitamin B12-dependent one-carbon metabolism is a limiting factor for diverse RAS/MAPK-induced cellular responses.
Autism candidate generbm-26(RBM26/27) regulates MALS-1 to protect against mitochondrial dysfunction and axon degeneration during neurodevelopment
Authors: Chowdhury Tamjid A , Luy David A , Scapellato Garrett , Farache Dorian , Lee Amy SY , Quinn Christopher C 
Published: October 2023

AbstractMitochondrial dysfunction is thought to be a key component of neurodevelopmental disorders such as autism, intellectual disability, and ADHD. However, little is known about the molecular mechanisms that protect against mitochondrial dysfunction during neurodevelopment. Here, we address this question through the investigation ofrbm-26, theC. elegansortholog of theRBM27autism candidate gene, which encodes an RNA-binding protein whose role in neurons is unknown. We report that RBM-26 (RBM26/27) protects against axonal defects by negatively regulating expression of the MALS-1 (MALSU1) mitoribosomal assembly factor. Autism-associated missense variants in RBM-26 cause a sharp decrease in RBM-26 protein expression along with defects in in axon overlap and axon degeneration that occurs during larval development. Using a biochemical screen, we identified the mRNA for the MALS-1 mitoribosomal assembly factor as a binding partner for RBM-26. Loss of RBM-26 function causes a dramatic overexpression ofmals-1mRNA and MALS-1 protein. Moreover, genetic analysis indicates that this overexpression of MALS-1 is responsible for the mitochondrial and axon degeneration defects inrbm-26mutants. These observations reveal a mechanism that regulates expression of a mitoribosomal assembly factor to protect against axon degeneration during neurodevelopment.
Effects of isochoric freezing on quality characteristics of raw bovine milk
Authors: Maida Alan , Bilbao-Sainz Cristina , Karman Andrew , Takeoka Gary , Powell-Palm Matthew J. , Rubinsky Boris 
Published: October 2023

AbstractThis study investigated the effects of isochoric freezing (IF) on the shelf-life and quality of raw bovine milk over a 5-week period. The results were compared with conventional refrigeration (RF) and refrigeration after pasteurization (HTST). The IF treatment process entailed storing liquid raw milk in isochoric chambers in thermodynamic equilibrium at -5°C /77MPa and -10°C /96MPa. Several parameters were analyzed, including microbiology count, physicochemical properties, indigenous enzyme activity, protein content, volatile organic compounds profile, and lipid degradation. Both raw and pasteurized milk experienced microbial level increases past the acceptable threshold (≥5.5 log CFU/mL) after 2 weeks and 5 weeks, respectively, leading to the deterioration of other parameters during storage. In comparison, microbiology count decreased significantly during storage for both IF treatment conditions but was more pronounced for the higher pressure (96MPa) treatment, leading to undetectable levels of microorganism after 5 weeks. IF treatment maintained stable pH, titratable acidity, viscosity, lipid oxidation, volatile profiles, total protein content, and lactoperoxidase activity throughout the storage period. Color was preserved during IF treatment at -5°C/77MPa; however, color was impacted during IF treatment at -10°C/96MPa. Protein structures were also modified during pressurized storage in both IF treatments. Overall, the study demonstrated that isochoric freezing could significantly increase the shelf-life of milk by reducing microbiology activity, whilst maintaining its nutritional content. These results underscore the potential role of isochoric freezing as a valuable tool in eliminating pathogens while maintaining quality characteristics similar to raw milk over long storage periods.
Emx2Lineage Tracing Reveals Antecedent Patterns of Planar Polarity in the Mouse Inner Ear
Authors: Goodrich Ellison J. , Deans Michael R. 
Published: October 2023

AbstractThe planar polarized organization of vestibular hair cells in the utricle and saccule is unique because these inner ear sensory organs contain two groups of hair cells with oppositely oriented stereociliary bundles that meet at a Line of Polarity Reversal (LPR). This organization allows the utricle or the saccule to detect motions directed in opposite directions, and is coordinated with patterns of neural innervation. EMX2 is a transcription factor that is only expressed by hair cells located on one side of the utricle or saccule where it reverses the orientation of their bundles and thereby establishes the position of the LPR. We generatedEmx2-CreERt2 transgenic mice for genetic lineage tracing and demonstrate robustEmx2expression at embryonic day 11.5 (E11.5), before hair cell specification, and when the nascent utricle and saccule have not yet segregated from a common prosensory domain. All hair cells derived fromEmx2-CreERt2 lineage tracing at E11.5 are restricted to one side of the LPR in the mature utricle or saccule indicating that an antecedent LPR may be established by EMX2 at that stage. Consistent with this,Emx2-CreERt2 lineage tracing at E11.5 inDrehermutant mice, where the utricle and saccule fail to segregate, labels a continuous field of cells distributed along one side of a fused utricular-saccular-cochlear organ. Altogether these observations reveal that the origin of the LPR is established in the developing prosensory domain, and that the presence or absence ofEmx2expression defines progenitor cells with distinct lineages that include hair cells with oppositely oriented stereociliary bundles.
Phytochemical Characterization of Bio-active Compounds in Hydroethanolic Extract ofElaeocarpus ganitrusleaves using HPLC, LC-MS, and HPTLC Analyses
Authors: Khushwaha Jyotsana , Joshi Alpana , Sharma Shiva , Das Subrata K. 
Published: October 2023

AbstractBioactive compounds have various applications in different industries, including food, pharmaceutical, and cosmetic industries, demonstrating the need to identify the best-standardized technique to screen the phytochemical profile of medicinal plants. This study aimed to characterize the bioactive compounds in the hydroethanolic extracts ofElaeocarpus ganitrusleaves using various analytical techniques: HPLC, LC-MS, and HPTLC. Air-dried leaves ofE. ganitruswere extracted with 70% ethanol. The phytochemical composition of crude extracts was analyzed by the High performance liquid chromatography (HPLC) method, and a total of 93 compounds, including 46 flavonoids, 17 phenols, 14 polyphenols, 3 phenolic acid, 3 phenolic glycosides, 2 flavonoid glycosides, 2 glycosides, 2 phenylpropanoid glycoside, 1 hydroxycinnamic acid, 1 lignan, 1 tannin, and 1 terpene glycoside were detected and quantified. The Liquid chromatography mass spectrometry (LC-MS) analyses identified 11 major eleven compounds: quercetin (803.0215 µg/L), gallic acid (726.13 µg/L), ferulic acid (652.34 µg/L), chlorogenic acid (651.021µg/L), pinocembrin (264.11 µg/L), p-aminobenzoic acid (251.021 µg/L), epicatechin (246.02 µg/L), catechin (161.51 µg/L), caffeic acid (123.31 µg/L), syringaldehyde (116.31 µg/L), and naringenin (106.31 µg/L). The chemical fingerprinting was carried out by high performance thin layer chromatography (HPTLC), and HPTLC fingerprint qualitatively revealed a predominant amount of gallic acid (48.64 %), curcumin (15.21 %), caffeic acid (12.19 %) and cinnamic acid (6.50 %). A significant amount of bioactive constituents in a hydroethanolic extract ofE. ganitrusleaves indicates the plant’s therapeutic potential, including antioxidant, anti-inflammatory, antidiabetic, anticancer, neuroprotective, and cardio-protective activities.
Safety of Monovalent BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and NVX-CoV2373 (Novavax) COVID-19 Vaccines in US Children Aged 6 months to 17 years
Authors: Hu Mao , Shoaibi Azadeh , Feng Yuhui , Lloyd Patricia C. , Wong Hui Lee , Smith Elizabeth R. , Amend Kandace L. , Kline Annemarie , Beachler Daniel C. , Gruber Joann F. , Mitra Mahasweta , Seeger John D. , Harris Charlalynn , Secora Alex , Obidi Joyce , Wang Jing , Song Jennifer , McMahill-Walraven Cheryl N. , Reich Christian , McEvoy Rowan , Do Rose , Chillarige Yoganand , Clifford Robin , Cooper Danielle D , Forshee Richard , Anderson Steven A. 
Published: October 2023

AbstractImportanceActive monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes that may not be identified in prelicensure trials.ObjectiveTo conduct near real-time monitoring of health outcomes following COVID-19 vaccination in the United States (US) pediatric population aged 6 months to 17 years.DesignWe evaluated 21 pre-specified health outcomes; 15 were sequentially tested through near real-time surveillance, and 6 were monitored descriptively within a cohort of vaccinated children. We tested for increased rate of each outcome following vaccination compared to a historical comparator cohort.SettingThis population-based study was conducted under the US Food and Drug Administration public health surveillance mandate using three commercial claims databases.ParticipantsChildren aged 6 months to 17 years were included if they received a monovalent COVID-19 vaccine dose before early 2023 and had continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window to the COVID-19 vaccination dose.ExposureExposure was defined as receipt of a monovalent BNT162b2, mRNA-1273, or NVX-CoV2373 COVID-19 vaccine dose. The primary analysis evaluated dose 1 and dose 2 combined, and secondary analyses evaluated each dose separately. Follow-up time was censored at death, disenrollment, end of risk window, end of study period, or a subsequent dose administration.Main OutcomesTwenty-one prespecified health outcomes.ResultsThe study included 4,102,016 enrollees aged 6 months to17 years. Thirteen of 15 outcomes sequentially tested did not meet the threshold for a statistical signal. In the primary analysis, myocarditis or pericarditis signals were detected following BNT162b2 vaccine in children aged 12-17 years old and seizures/convulsions signals were detected following vaccination with BNT162b2 and mRNA-1273 in children aged 2-4/5 years. However, in a post-hoc sensitivity analysis, the seizures/convulsions signal was sensitive to background rates selection and was not observed when 2022 background rates were selected instead of 2020 rates.Conclusions and RelevanceOf the two signaled outcomes, the myocarditis or pericarditis signals are consistent with previously published reports. The new signal detected for seizures/convulsions among younger children should be further investigated in a robust epidemiological study with better confounding adjustment.
Gender differences in PTSD severity and pain outcomes: baseline results from the LAMP trial
Authors: Friedman JK , Taylor BC , Campbell E Hagel , Allen K , Bangerter A , Branson M , Bronfort G , Calvert C , Cross LJS , Driscoll M , Evans R , Ferguson JE , Haley A , Hennessy S , Meis LA , Burgess DJ 
Published: October 2023

AbstractBackgroundPost-traumatic stress disorder (PTSD) and chronic pain are highly prevalent comorbid conditions. Veterans dually burdened by PTSD and chronic pain experience more severe outcomes compared to either disorder alone. Few studies have enrolled enough women Veterans to test gender differences in pain outcomes [catastrophizing, intensity, interference] by the severity of PTSD.AimExamine gender differences in the association between PTSD symptoms and pain outcomes among Veterans enrolled in a chronic pain clinical trial.MethodsParticipants were 421 men and 386 women Veterans with chronic pain who provided complete data on PTSD symptoms and pain outcomes. We used hierarchical linear regression models to examine gender differences in pain outcomes by PTSD symptoms.ResultsAdjusted multivariable models indicated that PTSD symptoms were associated with higher levels of pain catastrophizing (0.57, 95% CI [0.51, 0.63]), pain intensity (0.30, 95% CI [0.24, 0.37]), and pain interference (0.46, 95% CI [0.39, 0.52]). No evidence suggesting differences in this association were found in either the crude or adjusted models (all interaction p-values<0.05).ConclusionThese findings may reflect the underlying mutual maintenance of these conditions whereby the sensation of pain could trigger PTSD symptoms, particularly if the trauma and pain are associated with the same event. Clinical implications and opportunities testing relevant treatments that may benefit both chronic pain and PTSD are discussed.
Rationale, design, analysis plan and baseline characteristics of a cluster randomized controlled trial for management of salt intake and salt procurement in hypertensive individuals and households in rural Central India through a Community Health Worker delivered Behavior Change Communication Intervention
Authors: Nagi Raunaq Singh , Kumar Sanjeev , Prasad Pankaj 
Published: October 2023

AbstractBackgroundCardiovascular diseases (CVD) contribute to highest number of non-communicable diseases associated morbidity and mortality. Uncontrolled hypertension has been linked to development and progression of CVDs. The global age-standardized prevalence of hypertension in 30-79 years age group is 32% for women and 34% for men. Hypertension is a metabolic risk factor that is drastically affected by dietary salt. Excessive dietary salt consumption is a behavioral risk factor and has been a WHO global target for hypertension and CVD management. The per capita global and national dietary salt consumption estimates exceed the recommended cut-off of 5g/day. Apart from policy changes, dietary salt consumption reduction through health promotion activities has been mandated by WHO and initiated in many countries. Community health workers (CHWs) have been identified as a target cadre for successful implementation of health promotion interventions.We aim to ascertain the effectiveness of various counseling modes on relative reduction of per capita dietary salt intake and household salt procurement.MethodsAn open label, factorial, cluster-RCT was executed in rural central India. Intervention arms were individual, group and mixed (group followed by individual) counseling and one standard care arm.ResultsA total of 127 adult hypertensive individuals were recruited in the study. One CHW was considered as one cluster and a total of eight (8) clusters were randomized for the study. The baseline characteristics of the participants have been presented.ConclusionThe results of this trial will inform up on effectiveness of different modes of behavior change communication intervention on reducing dietary salt-intake and procurement.
Ex vivostructures from spinach leaves
Authors: Wang Jie , Johansen Nicolai Tidemand , Gamon Luke Francis , Zhao Ziyuan , Guo Zongxin , Wang Yong , Fuglsang Anja Thoe , Gourdon Pontus , Wang Kaituo 
Published: October 2023

AbstractEx vivostructure determination of macromolecules from native source is gaining increasing attention from the scientific community, as the method can be employed to dissect the function of important, multi-component molecular machines. However, the existingex vivoprocedures often require genome manipulation or availability high-affinity binders, limiting the general applicability. Here, we report simple yet robust principles for isolation of protein complexes from enriched native biological material, enabling cryoEM-facilitated high-resolution structure determination. We report the structures of ten separate membrane and soluble protein complexes determined from spinach leaves. Moreover, the developed pipeline is likely adaptable to essentially any biological system. As such, the approach may represent an attractive avenue for future structural proteomics efforts.
Actin-based deformations of the nucleus control multiciliated ependymal cell differentiation
Authors: Basso Marianne , Mahuzier Alexia , Ali Syed Kaabir , Marty Anaïs , Faucourt Marion , Lennon-Duménil Ana-Maria , Srivastava Ayush , Damaa Michella Khoury , Bankole Alexia , Meunier Alice , Yamada Ayako , Plastino Julie , Spassky Nathalie , Delgehyr Nathalie 
Published: October 2023

SUMMARYEpendymal cells (ECs) are multi-ciliated cells in the brain that contribute to cerebrospinal fluid flow. ECs are specified at embryonic stages but differentiate later in development. Differentiation depends on genes such as GEMC1 and MCIDAS with E2F4/5, but also on cell cycle related factors. In the mouse brain, we observe that nuclear deformation accompanies EC differentiation. Tampering with these deformations either by decreasing F-actin levels or by severing the link between the nucleus and the actin cytoskeleton blocks differentiation. Conversely, increasing F-actin by knocking out the Arp2/3 complex inhibitor Arpin or artificially deforming the nucleus activates differentiation. These data are consistent with actin polymerization triggering nuclear deformation and jump-starting the signaling that produces ECs. A player in this process is the retinoblastoma1 (RB1) protein whose phosphorylation prompts MCIDAS activation. Overall, this study reveals an important role for actin-based mechanical inputs to the nucleus as controlling factors in cell differentiation.
Antiviral capacity of the early CD8 T-cell response is predictive of natural control of SIV infection
Authors: Vemparala Bharadwaj , Madelain Vincent , Passaes Caroline , Millet Antoine , Avettand-Fenoel Véronique , Djidjou-Demasse Ramsès , Dereuddre-Bosquet Nathalie , Le Grand Roger , Rouzioux Christine , Vaslin Bruno , Sáez-Cirión Asier , Guedj Jérémie , Dixit Narendra M. 
Published: October 2023

ABSTRACTWhile most individuals suffer progressive disease following HIV infection, a small fraction spontaneously controls the infection. Although CD8 T-cells have been implicated in this natural control, their mechanistic roles are yet to be established. Here, we combined mathematical modeling and analysis of data from 16 SIV-infected macaques, of which 12 were natural controllers, to elucidate the role of CD8 T-cells in natural control. For each macaque, we considered, in addition to the canonicalin vivoplasma viral load and SIV DNA data, longitudinalex vivomeasurements of the virus suppressive capacity of CD8 T-cells. Available mathematical models do not allow analysis of such combinedin vivo-ex vivodatasets. By explicitly modeling theex vivoassay and integrating it within vivodynamics, we developed a new framework that enabled the analysis. Our model fit the data well and estimated that the recruitment rate and/or maximal killing rate of CD8 T-cells was up to 2-fold higher in controllers than non-controllers (p=0.013). Importantly, the cumulative suppressive capacity of CD8 T-cells over the first 4-6 weeks of infection was associated with virus control (Spearman’s ρ=- 0.51; p=0.05). Thus, our analysis identified the early cumulative suppressive capacity of CD8 T-cells as a predictor of natural control. Furthermore, simulating a large virtual population, our model quantified the minimum capacity of this early CD8 T-cell response necessary for long-term control. Our study presents new, quantitative insights into the role of CD8 T-cells in the natural control of HIV infection and has implications for remission strategies.
NanoRanger enables rapid single base-pair resolution of genomic disorders
Authors: Zhang Yingzi , Bi Chongwei , Nadeef Seba Saleh , Maddirevula Sateesh , Alqahtani Mashael , Alkuraya Fowzan S. , Li Mo 
Published: October 2023

ABSTRACTRare diseases affect around 350 million individuals globally, yet at least half of those with suspected Mendelian disorders remain without a precise molecular diagnosis despite advanced genetic testing using short read sequencing (SRS). Long-read sequencing (LRS) holds a promise in addressing this diagnostic gap although its clinical application is hampered by its complicated workflow, demanding sample requirements, and exorbitant cost. Genomic disorders represent an opportunity to demonstrate the unique capability of LRS. This study addresses the challenges of identifying missing disease-causing breakpoints in complex genomic disorders by employing multiple LRS strategies, including a novel strategy namednanopore-based rapidacquisition ofneighboringgenomic regions (NanoRanger). NanoRanger requires neither detailed prior genetic mapping nor large amounts of ultrahigh-molecular-weight DNA, and it stands out for its ease of use and ultra-rapid acquisition of large genomic regions of interest with deep coverage. We describe a cohort of 13 families, each harboring a different homozygous disease-causing genomic rearrangement that defied breakpoint determination by SRS and Optical Genome Mapping (OGM). In each case, NanoRanger identified the breakpoints with a single base-pair resolution. This has enabled the accurate determination of the carrier status of unaffected family members as well as the founder nature of these genomic lesions and their frequency in the local population. It has also enabled an unprecedented analysis of the DNA motifs to discern the mechanism that predisposed to these recessive rearrangements. Our data suggest that NanoRanger can greatly accelerate the clinical adoption of LRS and expand its access for the benefit of patients with rare diseases.