bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of the Serotonin Receptor 7 Restores Brain Histone H3 Acetylation and MeCP2 Corepressor Protein Levels in a Female Mouse Model of Rett Syndrome
Authors: Napoletani Giorgia , Vigli Daniele , Cosentino Livia , Grieco Maddalena , Talamo Maria Cristina , Lacivita Enza , Leopoldo Marcello , Laviola Giovanni , Fuso Andrea , d’Erme Maria , De Filippis Bianca 
Published: February 2021

Abstract
Rett syndrome (RTT) is a rare neurological disorder caused by mutations in the X-linked MECP2 gene, characterized by severe behavioral and physiological impairments for which no cure is available. The stimulation of serotonin receptor 7 (5-HT7R) with its selective agonist LP-211 (0.25 mg/kg/day for 7 days) was proved to rescue neurobehavioral alterations in a mouse model of RTT. In the present study, we aimed at gaining insight into the mechanisms underpinning the efficacy of 5-HT7R pharmacological stimulation by investigating its epigenetic outcomes in the brain of RTT female mice bearing a truncating MeCP2 mutation. Treatment with LP-211 normalized the reduced histone H3 acetylation and HDAC3/NCoR levels, and increased HDAC1/Sin3a expression in RTT mouse cortex. Repeated 5-HT7R stimulation also appeared to strengthen the association between NCoR and MeCP2 in the same brain region. A different profile was found in RTT hippocampus, where LP-211 rescued H3 hyperacetylation and increased HDAC3 levels. Overall, the present data highlight a new scenario on the relationship between histone acetylation and serotoninergic pathways. 5-HT7R is confirmed as a pivotal therapeutic target for the recovery of neuronal function supporting the translational value of this promising pharmacological approach for RTT.
Down-regulation of long non-coding RNA antisense non-coding RNA in the INK4 locus suppresses OVCAR-3 cells proliferation and induction of apoptosis by Wnt/β-catenin
Authors: Sun Lingna , Cui Yuping , Jiang Kongdi , Li Juan 
Published: February 2021

Abstract

Objectives
Ovarian cancer is a lethal gynecological malignancy. Long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) was reported to have a critical role in cancer advancement. The ANRIL-mediated oncogenic underlying molecular mechanisms are not fully understood in ovarian cancer. We aimed to study ANRIL silencing effects on the proliferation and apoptosis of OVCAR-3 cells.

Methods
The ANRIL was Knockdown by transfection of OVCAR-3 cells with si-RNA against ANRIL. MTT assay and cell death ELISA kit were used to evaluate cellular proliferation and apoptosis. The expression levels of ANRIL, pro-and anti-apoptotic genes were assessed using q-RT-PCR. Western blotting was used to assess Wnt/β-catenin signalling pathway.

Key findings
ANRIL down-regulating in OVCAR-3 cell lines resulted in significant inhibition of cellular proliferation, apoptosis induction, as well as suppression of cellular invasion. Besides, knockdown of ANRIL led to pro-apoptotic genes up-regulation, Bad and Bax and anti-apoptotic genes down-regulation, Bid and Bcl-2. More importantly, we observed that ANRIL inhibition suppressed the vital components expression of the Wnt/β-catenin cascade.

Conclusion
Our findings showed that down-regulation of lncRNA ANRIL resulted in the effective suppression of OVCAR-3 cell proliferation and invasion and induction of apoptosis by preventing Wnt/β-catenin signal transduction.
Association of SLC22A1,SLCO1B3 Drug Transporter Polymorphisms and Smoking with Disease Risk and Cytogenetic Response to Imatinib in Patients with Chronic Myeloid Leukemia
Authors: Mohammadi Fatemeh , Rostami Golale , Assad Dlnya , Shafiei Mohammad , Hamid Mohammad , Jalaeikhoo Hasan 
Published: February 2021

Abstract

Objective
To determine whether polymorphisms of SLC22A1 and SLCO1B3 genes could predict imatinib (IM) response and chronic myeloid leukemia (CML) risk.

Methods
We genotyped SLC22A1 (c.480G &gt; C, c.1222A &gt; G) and SLCO1B3 (c.334T &gt; G, c.699G &gt; A) polymorphisms in 132 patients with CML and 109 sex- and age-matched healthy subjects. The patients were evaluated for cytogenetic response by standard chromosome banding analysis (CBA).

Results
Polymorphism analysis showed significant increased risk of IM resistance for SLC22A1c.1222AG (P = .03; OR = 2.2), SLCO1B3c.334TT/TG genotypes (P = .007; OR = 4.37) and 334T allele (P = .03; OR = 2.86). The double combinations of SLC22A1c.480CC and c.1222AG polymorphisms with SLCO1B3c.334TT/TG were significantly associated with complete cytogenetic response (CCyR) (P &lt;.05; OR&gt; 7). The interaction between all polymorphisms and smoking were associated with CML development and IM resistance (P ≤.04; OR&gt; 3).

Conclusions
Our study results suggest the influence of SLC22A1 and SLCO1B3 polymorphisms and the interaction of smoking on CML development and IM response.
Downregulation of aromatase plays a dual role in preeclampsia
Authors: Zhu Dawei , Huang Jie , Gu Xing , Li Li , Han Jian 
Published: February 2021

AbstractPreeclampsia (PE) is a gestational disease, which seriously impairs maternal and infant health. However, the pathogenesis of PE remains unclear. The aromatase (CYP19A1) in placenta converts androgens from maternal and fetal adrenal glands to estrogen. Therefore, this change in the aromatase expression or function and the subsequent change of steroids in the placenta could be related to the pathophysiology of PE. In this study, we first analyzed the expression of CYP19A1 in clinical placental tissues as well as the level of sex hormones in corresponding serum samples. The results showed that the expression of aromatase in the placenta of PE patients was relatively low and accompanied by a sex hormone imbalance. Subsequently, animal experiments showed that ischemia and hypoxia lead to a low expression of CYP19A1, and that PE-like symptoms appear in pregnant mice following decreased or inhibited CYP19A1 expression. It was also found that, with the downregulation of CYP19A1 expression, the invasion and migration abilities of trophoblast cells were enhanced, which benefited placental implantation. However, alongside this, apoptosis and the inflammatory response were also increased, which was detrimental to placental development. Phosphoproteomic analyses revealed that the activation of the PI3K/AKT signaling pathway may play a key role in these processes. In conclusion, the downregulation of aromatase has a dual role in PE, among which the induction of the disease is the main role. Our study provides a potential novel method for the early prediction and treatment of PE.
Xenogeneic silencing relies on temperature-dependent phosphorylation of the host H-NS protein in Shewanella
Authors: Liu Xiaoxiao , Lin Shituan , Liu Tianlang , Zhou Yiqing , Wang Weiquan , Yao Jianyun , Guo Yunxue , Tang Kaihao , Chen Ran , Benedik Michael J , Wang Xiaoxue 
Published: February 2021

Abstract
Lateral gene transfer (LGT) plays a key role in shaping the genome evolution and environmental adaptation of bacteria. Xenogeneic silencing is crucial to ensure the safe acquisition of LGT genes into host pre-existing regulatory networks. We previously found that the host nucleoid structuring protein (H-NS) silences prophage CP4So at warm temperatures yet enables this prophage to excise at cold temperatures in Shewanella oneidensis. However, whether H-NS silences other genes and how bacteria modulate H-NS to regulate the expression of genes have not been fully elucidated. In this study, we discovered that the H-NS silences many LGT genes and the xenogeneic silencing of H-NS relies on a temperature-dependent phosphorylation at warm temperatures in S. oneidensis. Specifically, phosphorylation of H-NS at Ser42 is critical for silencing the cold-inducible genes including the excisionase of CP4So prophage, a cold shock protein, and a stress-related chemosensory system. By contrast, nonphosphorylated H-NS derepresses the promoter activity of these genes/operons to enable their expression at cold temperatures. Taken together, our results reveal that the posttranslational modification of H-NS can function as a regulatory switch to control LGT gene expression in host genomes to enable the host bacterium to react and thrive when environmental temperature changes.
MR1 overexpression correlates with poor clinical prognosis in glioma patients
Authors: Kubica Phillip , Lara-Velazquez Montserrat , Bam Marpe , Siraj Seema , Ong Irene , Liu Peng , Priya Raj , Salamat Shahriar , Brutkiewicz Randy R , Dey Mahua 
Published: February 2021

Abstract

Background
Glioblastoma is the most common adult primary brain tumor with near-universal fatality. Major histocompatibility complex (MHC) class I molecules are important mediators of CD8 activation and can be downregulated by cancer cells to escape immune surveillance. MR1 is a nonclassical MHC-I-like molecule responsible for the activation of a subset of T cells. Although high levels of MR1 expression should enhance cancer cell recognition, various tumors demonstrate MR1 overexpression with unknown implications. Here, we study the role of MR1 in glioma.

Methods
Using multi-omics data from the Cancer Genome Atlas (TCGA), we studied MR1 expression patterns and its impact on survival for various solid tumors. In glioma specifically, we validated MR1 expression by histology, elucidate transcriptomic profiles of MR1 high versus low gliomas. To understand MR1 expression, we analyzed the methylation status of the MR1 gene and MR1 gene-related transcription factor (TF) expression.

Results
MR1 is overexpressed in all grades of glioma and many other solid cancers. However, only in glioma, MR1 overexpression correlated with poor overall survival and demonstrated global dysregulation of many immune-related genes in an MR1-dependent manner. MR1 overexpression correlated with decreased MR1 gene methylation and upregulation of predicted MR1 promoter binding TFs, implying MR1 gene methylation might regulate MR1 expression in glioma.

Conclusions
Our in silico analysis shows that MR1 expression is a predictor of clinical outcome in glioma patients and is potentially regulated at the epigenetic level, resulting in immune-related genes dysregulation. These findings need to be validated using independent in vitro and in vivo functional studies.
Adolescent and young adult neuro-oncology: a comprehensive review
Authors: Yeo Kee Kiat , Burgers Darcy E , Brodigan Katelynn , Fasciano Karen , Frazier A Lindsay , Warren Katherine E , Reardon David A 
Published: February 2021

Abstract
Adolescent and young adult (AYA; ages 15-39) patients represent a population that experiences significant challenges in cancer care and research, exemplified by poorer clinical outcomes as well as unmet psychosocial and reproductive health needs. Despite central nervous system (CNS) tumors being one of the most common malignancies diagnosed in the age group, there is a clear paucity of AYA CNS tumor-specific publications, especially those related to the unique psychosocial and reproductive health needs of this population of patients. In this review, we examine various aspects of AYA oncological care including tumor biology, clinical outcome, clinical trials enrollment rate, site of care, unique psychosocial needs, and oncofertility. We assess the current state of these issues, highlight areas of deficiencies, and outline the steps needed to address these concerns. We emphasize the importance of comprehensive molecular testing as part of the diagnostic work-up, expansion of clinical trial availability, access to psychosocial care and oncofertility expertise, and the development of AYA-specific clinical research to define best practices and advancing care for this population.
The Response Measures to the Coronavirus Disease 2019 Outbreak in China
Authors: Qu Junyan , Lv Xiaoju 
Published: February 2021

Abstract
For China, the coronavirus disease 2019 (COVID-19) outbreak is a major public health emergency with the fastest spread, the most extensive infection, and the hardest to contain over the past 70 years. The different organizations and institutions in China have taken unprecedented public health responses to interrupt the virus transmission in the past several months. The outbreak in China was under control, but the number of confirmed cases abroad is still rising. Coronavirus disease 2019 has presented a global pandemic. We summarized the response measures adopted by different organizations at different levels (country, province, and hospital) in China, such as setting up an effective integrated system for disease prevention and control, effective deployment of medical staff, adjusting measures according to local conditions, establishing Fangcang hospitals, strengthening scientific research on COVID-19, epidemic prevention knowledge education, mass rapid testing for severe acute respiratory syndrome coronavirus 2, and correct personal protection including high compliance of wearing masks, hoping to provide some help for disease control in some regions.
Small business training to improve management practices in developing countries: re-assessing the evidence for ‘training doesn’t work’
Authors: McKenzie David 
Published: February 2021

Abstract Despite the popularity of business training among policy-makers, its use has faced increasing scepticism. Most of the first randomized experiments could not detect statistically significant impacts of training on firm profits or sales. I reassess the evidence for whether small business training works, incorporating more recent results. A meta-analysis of these estimates shows that training increases profits and sales on average by 5–10 per cent. This is in line with what is optimistic to expect, but impacts of this magnitude are too small for most experiments to detect. I then discuss five approaches for improving the effectiveness of traditional training by incorporating gender, kaizen methods, localization and mentoring, heuristics, and psychology. The challenge is then how to deliver a quality programme on a cost-effective basis at a much larger scale. Three possible approaches to scaling up training are discussed: using the market, using technology, or targeting and funnelling firms.
Stomatal morphology and physiology explain varied sensitivity to abscisic acid across vascular plant lineages
Authors: Gong Lei , Liu Xu-Dong , Zeng Yuan-Yuan , Tian Xue-Qian , Li Yan-Lu , Turner Neil C , Fang Xiang-Wen 
Published: February 2021

Abstract
Abscisic acid (ABA) can induce rapid stomatal closure in seed plants, but the action of this hormone on the stomata of fern and lycophyte species remains equivocal. Here, ABA-induced stomatal closure, signaling components, guard cell K+ and Ca2+ fluxes, vacuolar and actin cytoskeleton dynamics, and the permeability coefficient of guard cell protoplasts (Pf) were analyzed in species spanning the diversity of vascular land plants including 11 seed plants, 6 ferns, and 1 lycophyte. We found that all 11 seed plants exhibited ABA-induced stomatal closure, but the fern and lycophyte species did not. ABA-induced hydrogen peroxide elevation was observed in all species, but the signaling pathway downstream of nitric oxide production, including ion channel activation, was only observed in seed plants. In the angiosperm faba bean (Vicia faba), ABA application caused large vacuolar compartments to disaggregate, actin filaments to disintegrate into short fragments and Pf to increase. None of these changes was observed in the guard cells of the fern Matteuccia struthiopteris and lycophyte Selaginella moellendorffii treated with ABA, but a hypertonic osmotic solution did induce stomatal closure in fern and the lycophyte. Our results suggest that there is a major difference in the regulation of stomata between the fern and lycophyte plants and the seed plants. Importantly, these findings have uncovered the physiological and biophysical mechanisms that may have been responsible for the evolution of a stomatal response to ABA in the earliest seed plants.
Pitch and Duration Mismatch Negativity are Associated With Distinct Auditory Cortex and Inferior Frontal Cortex Volumes in the First-Episode Schizophrenia Spectrum
Authors: Curtis Mark T , Coffman Brian A , Salisbury Dean F 
Published: February 2021

Abstract

Background
Pitch and duration mismatch negativity (pMMN/dMMN) are related to left Heschl’s gyrus gray matter volumes in first-episode schizophrenia (FESz). Previous methods were unable to delineate functional subregions within and outside Heschl’s gyrus. The Human Connectome Project multimodal parcellation (HCP-MMP) atlas overcomes this limitation by parcellating these functional subregions. Further, MMN has generators in inferior frontal cortex, and therefore, may be associated with inferior frontal cortex pathology. With the novel use of the HCP-MMP to precisely parcellate auditory and inferior frontal cortex, we investigated relationships between gray matter and pMMN and dMMN in FESz.

Methods
pMMN and dMMN were measured at Fz from 27 FESz and 27 matched healthy controls. T1-weighted MRI scans were acquired. The HCP-MMP atlas was applied to individuals, and gray matter volumes were calculated for bilateral auditory and inferior frontal cortex parcels and correlated with MMN. FDR correction was used for multiple comparisons.

Results
In FESz only, pMMN was negatively correlated with left medial belt in auditory cortex and area 47L in inferior frontal cortex. Duration MMN negatively correlated with the following auditory parcels: left medial belt, lateral belt, parabelt, TA2, and right A5. Further, dMMN was associated with left area 47L, right area 44, and right area 47L in inferior frontal cortex.

Conclusions
The novel approach revealed overlapping and distinct gray matter associations for pMMN and dMMN in auditory and inferior frontal cortex in FESz. Thus, pMMN and dMMN may serve as biomarkers of underlying pathological deficits in both similar and slightly different cortical areas.
Banning Because of Science or In Spite of it? Scientific Authority, Religious Conservatism, and Support for Outlawing Pornography, 1984–2018
Authors: Perry Samuel L 
Published: February 2021

AbstractFor decades anti-pornography sentiment and campaigns were driven largely by religious conservatives citing pornography’s “contaminating” moral effects. More recently, however, anti-porn campaigns have sought to support their arguments by appealing to social and cognitive science. This raises the question of whether anti-pornography sentiment is undergoing an “internal secularization,” reflected in a growing connection to scientific authority and weakening connection to religious authority, or conversely, whether the use of “science” reflects a more symbolic and tactical framing used by religious conservatives who already oppose pornography. Using the General Social Surveys (1984–2018), I examine how trust in scientific authority and traditional measures of religious conservatism are associated with anti-pornography sentiment and how these associations have changed since the mid-1980s. The positive association between religious conservatism and support for anti-pornography legislation has either remained the same or, in the case of biblical literalism, grown stronger. In contrast, Americans with greater confidence in science or scientists are less likely to support outlawing pornography, and this pattern has not reversed. Indeed, in recent decades, Americans across all levels of confidence in science have declined in their support for banning porn and now differ only minimally. Together these patterns suggest anti-porn sentiment is actually desecularizing, growing more connected to religious conservatism than views about scientific authority. Findings suggest current anti-pornography sentiment does not stem from scientific authority gaining ground among Americans who oppose pornography. Rather, citing scientific research likely reflects efforts to leverage its cultural authority among those already morally inclined to restrict porn’s availability.
Mendelian randomization highlights insomnia as a risk factor for pain diagnoses
Authors: Broberg Martin , Karjalainen Juha ,   FinnGen, Ollila Hanna M 
Published: February 2021

Abstract

Study Objective
Insomnia has been linked to acute and chronic pain conditions; however, it is unclear whether such relationships are causal. Recently, a large number of genetic variants have been discovered for both insomnia and pain through genome-wide association studies (GWASs) providing a unique opportunity to examine the evidence for causal relationships through the use of the Mendelian randomization paradigm.

Methods
To elucidate the causality between insomnia and pain, we performed bidirectional Mendelian randomization analysis in FinnGen, where clinically diagnosed ICD-10 categories of pain had been evaluated. In addition, we used measures of self-reported insomnia symptoms. We used endpoints for pain in the FinnGen Release 5 (R5) (N = 218,379), and a non-overlapping sample for insomnia (UK Biobank (UKBB) and 23andMe, N = 1,331,010 or UKBB alone N = 453,379). We assessed the robustness of results through conventional Mendelian randomization sensitivity analyses.

Results
Genetic liability to insomnia symptoms increased the odds of reporting pain (odds ratio (OR) [95% confidence interval (CI)] = 1.47 [1.38–1.58], p = 4.12 × 10−28). Manifested pain had a small effect on increased risk for insomnia (OR [95% CI] = 1.04 [1.01–1.07], p &lt; 0.05). Results were consistent in sensitivity analyses.

Conclusions
Our findings support a bidirectional causal relationship between insomnia and pain. These data support a further clinical investigation into the utility of insomnia treatment as a strategy for pain management and vice versa.
Sleep quality deterioration in middle-aged and older adults living in a rural Ecuadorian village severely struck by the SARS-CoV-2 pandemic. A population-based longitudinal prospective study
Authors: Del Brutto Oscar H , Mera Robertino M , Costa Aldo F , Recalde Bettsy Y , Castillo Pablo R 
Published: February 2021

AbstractStudy ObjectivesThis study assessed changes in sleep quality before and after the peak of the SARS-CoV-2 pandemic in community dwellers enrolled in the Atahualpa Project.MethodsAtahualpa residents aged ≥40 years were eligible if they had a Pittsburgh Sleep Quality Index (PSQI) 9 months before the pandemic and a lateral flow-based test for identification of SARS-CoV-2 antibodies during the peak of the pandemic. Six months later, individuals completed a follow-up PSQI. The independent relationship between SARS-CoV-2 infection and deterioration in sleep quality was assessed by fitting logistic mixed models for longitudinal data.ResultsOf 639 participants (mean age at baseline: 59 ± 12.8 years), 325 (51%) had SARS-CoV-2 antibodies. A total of 185 (29%) individuals at baseline and 311 (49%) at follow-up were poor sleepers (p &lt; 0.001). Mixed logistic regression models demonstrated a significant increase in poor sleepers at follow-up (odds ratio [OR]: 2.85; 95% CI: 2.16 to 3.75), which was more marked among SARS-CoV-2 seropositive subjects (OR: 3.8; 95% CI: 2.48 to 5.81). The adjusted proportion of poor sleepers increased from 29% to 56.2% (95% CI: 50.9% to 61.6%) among SARS-CoV-2 seropositive individuals, but only to 40.7% (95% CI: 35.3% to 46.1%) in their seronegative counterparts (p &lt; 0.001). Likewise, progression from a good to a poor sleeper status was higher among seropositive individuals than in their seronegative counterparts (38.1% vs 22.3%; p &lt; 0.001), after adjusting for relevant covariates.ConclusionsThis study shows a deleterious effect of SARS-CoV-2 in sleep quality. An effect of SARS-CoV-2 in disrupting sleep-related pathways cannot be ruled out.Trial registrationThe Atahualpa Project has been registered at ClinicalTrials.gov; the identifier number is NCT01627600, and the date was: 10/02/2012 (https://clinicaltrials.gov/ct2/show/NCT01627600?cond=Atahualpa&draw=2&rank=1). The Sleep Disorders substudy has been registered at ClinicalTrials.gov; the identifier number is NCT01877616, and the date was: 06/13/2013 (https://clinicaltrials.gov/ct2/show/NCT01877616?cond=Atahualpa&draw=2&rank=4).