bluuebunny/crossref_metadata_2025_split huggingface dataset:
TASOR expression in naive embryonic stem cells safeguards their developmental potential
Authors: Pinzon-Arteaga Carlos A. , O’Hara Ryan , Mazzagati Alice , Ballard Emily , Hu Yingying , Pan Alex , Schmitz Daniel A. , Wei Yulei , Sakurai Masahiro , Ly Peter , Banaszynski Laura , Wu Jun 
Published: March 2024

AbstractThe seamless transition through stages of pluripotency relies on a delicate balance between transcription factor networks and epigenetic silencing mechanisms that ensure proper regulation of the developmental program, critical for normal development. Here, we uncover the pivotal role of the transgene activation suppressor (TASOR), a component of the human silencing hub (HUSH) complex, in sustaining cell viability during the transition from naive to primed pluripotency, despite its rapid downregulation during this transition. Loss of TASOR in naive cells triggers replication stress, disrupts H3K9me3 heterochromatin formation, and compromise the transcriptional and post-transcriptional silencing of LINE-1 (L1) transposable elements (TEs), with these effects become more pronounced in primed cells. Remarkably, the survival ofTasor-knockout cells during naive to primed transition can be restored through the inhibition of cysteine-aspartic acid protease (Caspase) or deletion of mitochondrial antiviral signaling protein (MAVS). This suggests that unscheduled L1 expression activates an innate immune response, leading to programmed cell death, specifically in cells exiting naïve pluripotency. Additionally, we propose that HUSH-promoted H3K9me3 in naïve PSCs sets the stage for ensuing DNA methylation in primed cells, establishing long-term silencing during differentiation. Our findings shed insights on the crucial impact of epigenetic programs established in early developmental stages on subsequent phases, underscoring their significance in the developmental process.
Changes of urinary proteome in rats after intragastric administration of calcium gluconate
Authors: Shen Ziyun , Yang Minhui , Wang Haitong , Gao Youhe 
Published: March 2024

AbtractCalcium is an essential element for maintaining the normal physiological function of organisms. In this study, 3225 mg/kg/d calcium gluconate (equivalent to 300 mg/kg/d calcium) was intragastrically administered to rats for 4 days, and the urine proteome of rats was analyzed. Many differential proteins have been reported to be calcium related, such as Regucalcin (2.6 times higher after gavage than before gavage, p = 0.022), transmembrane protein 132A (8.2 times higher after gavage than before gavage, p = 0.009), creatine kinase (17.5 times higher before gavage than after gavage, p = 0.006), and claudin-3 (13.3 times higher before gavage than after gavage, p = 0.037). Differential protein enriched KEGG pathways included calcium signaling pathways, and biological processes and molecular functions also showed correlation with calcium. In this study, from the perspective of urine proteomics to explore the overall impact of calcium on the body, it is helpful to deeply understand the biological function of calcium and broaden the application potential of urine proteomics.
SUN2 mediates calcium-triggered nuclear actin polymerization to cluster active RNA polymerase II
Authors: Ulferts Svenja , Grosse Robert 
Published: March 2024

AbstractThe nucleoskeleton is essential for nuclear architecture as well as genome integrity and gene expression. In addition to lamins, titin or spectrins, dynamic actin filament polymerization has emerged as a potential intranuclear structural element but its functions are less well explored. Here we found that calcium elevations trigger rapid nuclear actin assembly requiring the nuclear membrane protein SUN2 independently of its function as a component of the LINC complex. Instead, SUN2 colocalized and associated with the formin and actin nucleator INF2 in the nuclear envelope in a calcium-regulated manner. Moreover, SUN2 is required for active RNA polymerase II (RNA Pol II) clustering in response to calcium elevations. Thus, our data uncover a SUN2-formin module linking the nuclear envelope to intranuclear actin assembly to promote signal-dependent spatial reorganization of active RNA Pol II.
Eukaryotic initiation factor 3F (eIF3F) regulates the IRES-mediated translation of Bcl-xL via its interaction with programmed cell death 4 (PDCD4) protein
Authors: Hegde Veda , Sharma Divya K. , Patel Harshil , Narasimha Pavan , Luddu Jason , Holcik Martin , Thakor Nehal 
Published: March 2024

AbstractProgrammed cell death 4 (PDCD4) protein is a well-characterized tumor suppressor protein. PDCD4 inhibits mRNA translation by inhibiting the activity of an RNA helicase, eukaryotic initiation factor 4A (eIF4A). We have previously reported that PDCD4 interacts with the internal ribosome entry site (IRES) element that is found within the 5’ untranslated region (UTR) of mRNA encoding B-cell lymphoma extra-large (Bcl-xL) protein. PDCD4’s interaction with the Bcl-xL IRES element inhibits the IRES-mediated translation initiation on Bcl-xL mRNA. However, S6 kinase (S6K)-mediated phosphorylation of PDCD4 activates its degradation by proteasomal degradation pathway and derepress IRES-mediated translation initiation of Bcl-xL mRNA. Interestingly, eIF3F (one of the 13 subunits of eIF3) was reported to recruit S6K to phosphorylate eIF3. Therefore, we were intrigued by the possibility of co-regulation of PDCD4 and eIF3F by S6K and the regulation of IRES-mediated translation initiation by PDCD4-eIF3F. To this end, using co-immunoprecipitation (co-IP), we demonstrated that PDCD4 interacts with several subunits of eIF3. Reciprocal co-IP, endogenous IP, andin vitropull-down assays demonstrated that eIF3F directly interacts with PDCD4 in an RNA-independent manner. In order to functionally characterize the PDCD4-eIF3F complex, we depleted PDCD4 from the glioblastoma (GBM) cells, which resulted in decreased levels of eIF3F. Also, depletion of eIF3F from GBM cells reduced the levels of PDCD4 protein. However, this was not observed in non-cancer cells. Overexpression of PDCD4 resulted in enhanced levels of eIF3F, andvice versa. We further confirmed that the interaction of eIF3F and PDCD4 proteins prevents each other’s proteasomal degradation. By performing RNA-IP, we showed that PDCD4 and eIF3F interact with Bcl-xL RNA independently. Moreover, our IRES-bi-cistronic reporter assay and polysome profiling experiments demonstrated that eIF3F regulates IRES-mediated translation of Bcl-xL mRNA, likely via its interaction with PDCD4.SignificanceThis study uncovers the fundamental mechanism of the internal ribosome entry site (IRES)- mediated translation regulation of B-cell lymphoma extra-large (Bcl-xL) mRNA by programmed cell death 4 (PDCD4) protein, and the eukaryotic initiation factor 3F (eIF3F). Our results show that PDCD4 and eIF3F interact with each other directly and they also interact with Bcl-xL mRNA independently. We show that PDCD4 works via eIF3F to regulate Bcl-xL levels. We also show that the PDCD4-eIF3F-dependent mechanism of Bcl-xL mRNA translation is implicated in glioblastoma (GBM) cells, including the primary brain tumor stem cells (BTSCs), and would likely affect the GBM pathophysiology.
Flame-forged divergence? Ancient human fires and the evolution of diurnal and nocturnal lineages in Mediterranean geckos
Authors: Fulgione Domenico , Russo Danilo , Rivieccio Eleonora , Maselli Valeria , Avallone Bice , Mondanaro Alessandro , Giurato Giorgio , Buglione Maria 
Published: March 2024

AbstractHuman influence has historically exerted a major driving in creating novel ecological niches. Although the controlled use of fire by ancient humans probably played a significant role by attracting positive phototactic prey and favour foraging by insectivorous vertebrates, no study has ever explored this possibility. Using a multidisciplinary approach, we explore whether human-controlled fire has historically affected the temporal niche partitioning in two lineages of Moorish geckosTarentola mauritanica, a diurnal- dark form and a nocturnal-pale form. We showed that the nocturnal-pale variant possesses lower skin melanin for fewer and smaller melanosomes and experiences lower α-MSH plasmatic levels than its diurnal-dark counterpart. Additionally, the analysis of the full mitochondrial genome established that our pale-nocturnal lineage emerged around 40,000 years ago, i.e., 20,000 years before the dark-diurnal lineage. Both variants arose when modern humans expanded into Europe, coinciding with the widespread use of fire, which likely facilitated the availability of arthropod prey for pale geckos, opening a previously untapped niche. Our modelling exercises corroborated a highly probable human-geckos coexistence during the emergence of these lineages. Furthermore, we experimentally demonstrated that fire near a rock surface significantly increases the abundance of arthropod prey, attracting preferred prey for the pale variant during nocturnal foraging. We suggest that ancient fires likely provided a novel foraging niche for pale geckos, yet it remains unclear whether the two lineages originated from diurnal or nocturnal ancestors. We present two alternative interpretations: the “out of the dark” scenario proposes a nocturnal ancestor leading to a diurnal descendant, while the “into the dark” scenario suggests a dark-diurnal ancestor evolving into a pale-nocturnal lineage. Phenotypic plasticity emerges as a critical factor in both scenarios, facilitating adaptation to new environments. We underscore the ongoing impact of artificial lighting on nocturnal behaviour, offering parallels to the potential origins of the gecko’s nocturnal lineage.
Comparative efficacy and acceptability of treatment strategies for antipsychotic-induced akathisia: a systematic review and network meta-analysis
Authors: Furukawa Yuki , Imai Kota , Takahashi Yusuke , Efthimiou Orestis , Leucht Stefan 
Published: March 2024

ABSTRACTBackgroundAntipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia remains unclear.DesignWe performed a systematic review and network meta-analyses (PROSPERO CRD42023450720). We searched multiple databases on 24th July 2023. We included randomized clinical trials comparing one or more treatment strategies for antipsychotic-induced akathisia against each other or control conditions. We included adults with schizophrenia or other psychiatric disorders treated with antipsychotics. The primary outcome was akathisia severity at posttreatment. Secondary outcomes included akathisia response, all-cause dropout, psychotic symptoms, and long-term akathisia severity. We synthesized data in random effects frequentist network meta-analyses and assessed confidence in the evidence using CINeMA.ResultsWe identified 19 trials with 661 randomized participants (mean age 35.9 [standard deviation 12.0]; 36.7 % [195 of 532] women). No trials examined dose-reduction or switching of antipsychotics. Findings suggested 5-HT2A antagonists (k=6, n=108; standardized mean difference [SMD] -1.07 [95% confidence interval, -1.42; -0.71]) and beta-blockers (k=8, n=105; SMD -0.46 [-0.85; -0.07]) may improve akathisia severity, but confidence in the evidence was deemed low. We also found that benzodiazepines (k=2, n=13; SMD -1.62 [-2.64; -0.59]) and vitamin B6 (k=3, n=67; SMD -0.99 [-1.49; -0.50]) might also be beneficial, but confidence in the evidence was very low. Analyses of secondary outcomes did not provide additional insights.ConclusionsOur findings suggest that 5-HT2A antagonists, beta blockers, and with a lesser certainty, benzodiazepines and vitamin B6 might improve akathisia. These conclusions are extremely preliminary and further trials are needed.
The concurrent development of psychological distress, heavy episodic drinking, and daily smoking from adolescence to midlife in two cohorts
Authors: Berg Noora , Piirtola Maarit , Marttunen Mauri , Latvala Antti , Kiviruusu Olli 
Published: March 2024

AbstractBackgroundHeavy substance use, such as alcohol and tobacco use, is more prevalent among people with poor mental health. Despite the well-established correlation between substance use and mental health, the development of this association over time is unclear. The aim of this study was to examine the development and co-occurrence of psychological distress (mainly depressive and anxiety symptoms), heavy episodic drinking (HED) and daily smoking from adolescence to adulthood.MethodsTwo prospective longitudinal studies, the Stress, Development and Mental Health Study (TAM, N=2194) and the FinnTwin16 Study (N=5563), have followed participants from adolescence to adulthood (TAM ages 16-52, FinnTwin16 ages 16-35) using survey questionnaires. Latent class analysis was used to obtain joint trajectories of distress, HED and daily smoking.ResultsThis study identified several different patterns of how HED, daily smoking and psychological distress cluster across time from adolescence to adulthood. In both examined cohorts, distinct groups of i) low levels of all three examined health concerns, ii) high levels of all three concerns, and iii) high distress and low-to-moderate substance use were found. In the older TAM cohort with longer follow-up time, a group indicating iv) increasing HED and a group indicating v) all on average level, with a peak in smoking, were also found.ConclusionsFound variations set requirements for substance use and mental health services to target interventions for different groups to address all three major public health problems.
The impact of different antimicrobial exposures on the gut microbiome in the ARMORD observational study
Authors: Peto Leon , Fawcett Nicola , Kamfose Musaiwale M , Scarborough Claire , Peniket Andy , Danby Robert , Peto Tim EA , Crook Derrick W , Llewelyn Martin J , Sarah Walker A 
Published: March 2024

AbstractBackgroundBetter metrics to compare the impact of different antimicrobials on the gut microbiome would aid efforts to control antimicrobial resistance (AMR).MethodsThe Antibiotic Resistance in the Microbiome – Oxford (ARMORD) study recruited inpatients, outpatients and healthy volunteers in Oxfordshire, UK, who provided stool samples for metagenomic sequencing. Data on previous antimicrobial use and potential confounders were recorded. Exposures to each antimicrobial were considered as factors in a multivariable linear regression, also adjusted for demographics, with separate analyses for those contributing samples cross-sectionally or longitudinally. Outcomes were Shannon diversity and relative abundance of specific bacterial taxa (Enterobacteriaceae,Enterococcus, and major anaerobic groups) and antimicrobial resistance genes (targeting beta-lactams, tetracyclines, aminoglycosides, macrolides, and glycopeptides).Results225 adults were included in the cross-sectional analysis, and a subset of 79 patients undergoing haematopoietic stem cell transplant provided serial samples for longitudinal analysis. Results were largely consistent between the two sampling frames. Recent use of piperacillin-tazobactam, meropenem, intravenous co-amoxiclav and clindamycin were associated with large reductions in microbiome diversity and reduced abundance of anaerobes. Exposure to piperacillin-tazobactam and meropenem were associated with a decreased abundance ofEnterobacteriaceae, and an increased abundance ofEnterococcusand major AMR genes, but there was no evidence that these antibiotics had a greater impact on microbiome diversity than iv co-amoxiclav or oral clindamycin. In contrast, co-trimoxazole, doxycycline, antifungals and antivirals had less impact on microbiome diversity and selection of AMR genes.ConclusionSimultaneous estimation of the impact of over 20 antimicrobials on the gut microbiome and AMR gene abundance highlighted important differences between individual drugs. Some drugs in the WHO Access group (co-amoxiclav, clindamycin) had similar magnitude impact on microbiome diversity to those in the Watch group (meropenem, piperacillin-tazobactam) with potential implications for acquisition of resistant organisms. Metagenomic sequencing can be used to compare the impact of different antimicrobial agents and treatment strategies on the commensal flora.
Comprehensive knowledge and positive attitudes regarding HIV/AIDS among reproductive-aged women in Bangladesh and their associated factors: a cross-sectional study using the Multiple Indicator Cluster Survey 2019
Authors: Billah Md Arif , Yusof Raba’Aton Adawiah Mohd , Khan Md. Nuruzzaman , Min Ruhani Mat 
Published: March 2024

AbstractBackgroundHIV/AIDS remains a global health concern and understanding the knowledge and attitudes of at-risk populations is crucial for effective prevention and management. This study examines the knowledge and attitudes related to HIV/AIDS among reproductive-aged women in Bangladesh and explores associated factors.MethodsThe study analyzed data from a total of 39,066 reproductive women, obtained from the nationally representative 2019 Multiple Indicator Cluster Survey. The outcome variables assessed were the level of HIV/AIDS-related knowledge (highvslow) and attitudes regarding HIV/AIDS (goodvspoor). These variables were derived by calculating the median values of scores obtained from nine and six questions in the survey that assessed knowledge and attitudes toward HIV/AIDS, respectively. The explanatory variables included sociodemographic factors and variables related to media exposure. A multivariate logistic regression model was employed to investigate the associations between the outcome and explanatory variables.ResultsOver half of the total respondents (51.6%) reported a lower level of knowledge, and a significant majority (54.2%) exhibited poor attitudes regarding HIV/AIDS, with notable variations observed across districts. Women in comparatively higher age groups, those with higher levels of education, hailing from more affluent families, residing in urban areas, and having exposure to newspapers, the internet, computers, and mobile phones displayed higher levels of knowledge regarding HIV/AIDS. Conversely, women with higher education levels, residing in rural areas, and having exposure to mobile phones and the internet exhibited good attitudes regarding HIV/AIDS. Unmarried respondents reported lower likelihoods of good attitude towards HIV/AIDS.ConclusionThe findings underscores the urgent need for policies and programs designed to improve HIV/AIDS-related knowledge and attitudes, with a focus on district-level requirements. Effective strategies may include mass media campaigns and the incorporation of HIV/AIDS- related topics into the national curriculum.
TheEIF4EBP1gene encoding 4EBP1 is transcriptionally upregulated by MYC and linked to shorter survival in medulloblastoma
Authors: Hruby Laura , Scharov Katerina , Delaidelli Alberto , Picard Daniel , Dunham Christopher , Lewandowska Oksana , Reiff Tobias , Larcher Magalie , Pouponnot Celio , Sorensen Poul HB , Rotblat Barak , Reifenberger Guido , Remke Marc , Leprivier Gabriel 
Published: March 2024

ABSTRACTMedulloblastoma (MB) is the most common malignant brain tumor in childhood and is stratified into four molecular groups ‒ WNT, SHH, Group 3 and Group 4. Group 3 MB patients exhibit the poorest prognosis, with a 5-year overall survival of <60%, followed by Group 4 MB patients. Apart fromMYCamplification in a subset of Group 3 MBs, the molecular pathomechanisms driving aggressiveness of these tumors remain incompletely characterized. The gene encoding the mTOR substrate and mRNA translation inhibitor eukaryotic translation initiation factor 4E-binding protein 1 (EIF4EBP1) represents a possible MYC target gene whose corresponding protein, 4EBP1, was shown to be more active in Group 3 versus Group 4 MBs. However, the prognostic role of 4EBP1 in MB and the mechanisms supporting 4EBP1 overexpression in Group 3 MB are still elusive. We analyzedEIF4EBP1mRNA expression in publicly available data sets and found an upregulation in MB as compared to non-neoblastic brain.EIF4EBP1mRNA expression levels were higher in Group 3 compared to Group 4 MBs.EIF4EBP1mRNA expression was correlated withMYCexpression, most prominently in Group 3 MBs. Survival analyses highlighted that highEIF4EBP1mRNA expression was associated with reduced overall and event-free survival across all MB patients and in Group 3/Group 4 MB patients. Immunohistochemical evaluation of 4EBP1 protein expression in MB tissues confirmed that high levels of 4EBP1 are associated with poor outcome. Functional analyses revealed that MYC directly regulatesEIF4EBP1promoter activity, providing a mechanism for increasedEIF4EBP1mRNA levels in Group 3 MBs. Finally, we observed that 4EBP1 may support colony formation ofin vitrocultured MB cells. Our data highlight that transcriptional upregulation ofEIF4EBP1by MYC promotesin vitrotumorigenicity of MB cells and associates with shorter survival of MB patients.
Growing up in poverty, growing old in frailty: The life course shaping of health in America, Britain, and Europe – a prospective and retrospective study
Authors: Tampubolon Gindo 
Published: March 2024

AbstractBackgroundChildhood poverty is directly associated with many health outcomes in late life irrespective of youth health and of variation in health systems. The childhood poor in America, Britain and Europe have reported worse cognitive, muscle and mental functions in their fifties to nineties. But it is not known whether they have higher probabilities of experiencing frailty as their childhood recollections are likely to be erroneous.Materials and methodsSome 79428 adults aged 50 and older retrospectively recalled their childhood conditions at ten and underwent prospective examinations to construct their Fried’s frailty phenotype. Childhood conditions in ELSA and SHARE include number of books, number of rooms, number of people, presence of running hot or cold water, fixed bath, indoor lavatory and central heating. Across in America, these are mostly replaced with financial hardship indicators including having to move because of family debt. Childhood poverty is a latent construct of error-laced recollection and its distal fully adjusted association with frailty phenotype is estimated with fixed effects probit model.ResultsChildhood poverty associates with higher probabilities of being frail (0.1097 ± 0.0169, p < 0.001) in 29 countries of America, Britain and Europe. Furthermore, women have higher probabilities of being frail (0.3051 ± 0.0152, p < 0.001). Age, education, wealth, marital status and youth illness exert influences on the probabilities of being frail. Sensitivity analyses were conducted using random effects model and by stratifying on sex.DiscussionEvidence is mounting that childhood can last a life time, affecting cognitive and muscle function, mental health and now frailty. This evidence calls for urgent actions to eliminate child poverty on account of its lifelong rewards. (271 + 4476 words)