bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer cells escape p53’s tumor suppression through ablation of ZDHHC1-mediated p53 palmitoylation
Authors: Tang Jun , Peng Weiyan , Feng Yixiao , Le Xin , Wang Kang , Xiang Qin , Li Lili , Wang Yan , Xu Can , Mu Junhao , Xu Ke , Ji Ping , Tao Qian , Huang Ailong , Deng Chu-Xia , Lin Yong , Xiang Tingxiu 
Published: July 2021

AbstractThe inactivation of tumor-suppressor genes contributes heavily to oncogenesis. The mutation of TP53 has been well-studied and recognized as a major factor in the development of tumors. Yet other means of p53 inactivation has not been well-elucidated. We previously identified a hypermethylated gene ZDHHC1 that suppresses tumor growth when the expression was restored, but the specific mechanism was yet to be found. The protein product of ZDHHC1 is an S-palmitoyltransferase and we have identified p53 as a substrate for ZDHHC1-mediated palmitoylation, specifically at the C135, C176, and C275 residues. The novel form of post-translational modification of p53 is required for the nuclear translocation of the tumor suppressor. p53 recruited DNMT3A to ZDHHC1 promoter and is responsible for the hypermethylation of ZDHHC1. The epigenetic feedback loop formed by ZDHHC1 and p53 sheds light on the inactivation of p53 without the presence of genetic mutations.
Adversity in early life and pregnancy are immunologically distinct from total life adversity: macrophage-associated phenotypes in women exposed to interpersonal violence
Authors: Aschbacher Kirstin , Hagan Melissa , Steine Iris M. , Rivera Luisa , Cole Steve , Baccarella Alyssa , Epel Elissa S. , Lieberman Alicia , Bush Nicole R. 
Published: July 2021

AbstractEarly childhood and pregnancy are two sensitive periods of heightened immune plasticity, when exposure to adversity may disproportionately increase health risks. However, we need deeper phenotyping to disentangle the impact of adversity during sensitive periods from that across the total lifespan. This study examined whether retrospective reports of adversity during childhood or pregnancy were associated with inflammatory imbalance, in an ethnically diverse cohort of 53 low-income women seeking family-based trauma treatment following exposure to interpersonal violence. Structured interviews assessed early life adversity (trauma exposure ≤ age 5), pregnancy adversity, and total lifetime adversity. Blood serum was assayed for pro-inflammatory (TNF-a, IL-1ß, IL-6, and CRP) and anti-inflammatory (IL-1RA, IL-4, and IL-10) cytokines. CD14+ monocytes were isolated in a subsample (n = 42) and gene expression assayed by RNA sequencing (Illumina HiSeq 4000; TruSeq cDNA library). The primary outcome was a macrophage-associated M1/M2 gene expression phenotype. To evaluate sensitivity and specificity, we contrasted M1/M2 gene expression with a second, clinically-validated macrophage-associated immunosuppressive phenotype (endotoxin tolerance) and with pro-inflammatory and anti-inflammatory cytokine levels. Adjusting for demographics, socioeconomic status, and psychopathology, higher adversity in early life (ß = .337, p = 0.029) and pregnancy (ß = .332, p = 0.032) were each associated with higher M1/M2 gene expression, whereas higher lifetime adversity (ß = −.341, p = 0.031) was associated with lower immunosuppressive gene expression. Adversity during sensitive periods was uniquely associated with M1/M2 imbalance, among low-income women with interpersonal violence exposure. Given that M1/M2 imbalance is found in sepsis, severe COVID-19 and myriad chronic diseases, these findings implicate novel immune mechanisms underlying the impact of adversity on health.
Impact of COVID-19 lockdown on mental health in Germany: longitudinal observation of different mental health trajectories and protective factors
Authors: Ahrens K. F. , Neumann R. J. , Kollmann B. , Brokelmann J. , von Werthern N. M. , Malyshau A. , Weichert D. , Lutz B. , Fiebach C. J. , Wessa M. , Kalisch R. , Plichta M. M. , Lieb K. , Tüscher O. , Reif A. 
Published: July 2021

AbstractThe COVID-19 pandemic and resulting measures can be regarded as a global stressor. Cross-sectional studies showed rather negative impacts on people’s mental health, while longitudinal studies considering pre-lockdown data are still scarce. The present study investigated the impact of COVID-19 related lockdown measures in a longitudinal German sample, assessed since 2017. During lockdown, 523 participants completed additional weekly online questionnaires on e.g., mental health, COVID-19-related and general stressor exposure. Predictors for and distinct trajectories of mental health outcomes were determined, using multilevel models and latent growth mixture models, respectively. Positive pandemic appraisal, social support, and adaptive cognitive emotion regulation were positively, whereas perceived stress, daily hassles, and feeling lonely negatively related to mental health outcomes in the entire sample. Three subgroups (“recovered,” 9.0%; “resilient,” 82.6%; “delayed dysfunction,” 8.4%) with different mental health responses to initial lockdown measures were identified. Subgroups differed in perceived stress and COVID-19-specific positive appraisal. Although most participants remained mentally healthy, as observed in the resilient group, we also observed inter-individual differences. Participants’ psychological state deteriorated over time in the delayed dysfunction group, putting them at risk for mental disorder development. Consequently, health services should especially identify and allocate resources to vulnerable individuals.
Longitudinal genome-wide methylation study of PTSD treatment using prolonged exposure and hydrocortisone
Authors: Yang Ruoting , Xu Changxin , Bierer Linda M. , Flory Janine D. , Gautam Aarti , Bader Heather N. , Lehrner Amy , Makotkine Iouri , Desarnaud Frank , Miller Stacy A. , Jett Marti , Hammamieh Rasha , Yehuda Rachel 
Published: July 2021

AbstractEpigenetic changes are currently invoked as explanations for both the chronicity and tenacity of post-traumatic stress disorder (PTSD), a heterogeneous condition showing varying, sometimes idiosyncratic responses to treatment. This study evaluated epigenetic markers in the context of a randomized clinical trial of PTSD patients undergoing prolonged-exposure psychotherapy with and without a hydrocortisone augmentation prior to each session. The purpose of the longitudinal epigenome-wide analyses was to identify predictors of recovery (from pretreatment data) or markers associated with symptom change (based on differences between pre- and post-therapy epigenetic changes). The results of these analyses identified the CREB–BDNF signaling pathway, previously linked to startle reaction and fear learning and memory processes, as a convergent marker predicting both symptom change and severity. Several previous-reported resilience markers were also identified (FKBP5, NR3C1, SDK1, and MAD1L1) to associate with PTSD recovery in this study. Especially, the methylation levels of FKBP5 in the gene body region decreased significantly as CAPS score decreased in responders, while no changes occurred in nonresponders. These biomarkers may have future utility in understanding clinical recovery in PTSD and potential applications in predicting treatment effects.
The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study
Authors: Onwordi Ellis Chika , Whitehurst Thomas , Mansur Ayla , Statton Ben , Berry Alaine , Quinlan Marina , O’Regan Declan P. , Rogdaki Maria , Marques Tiago Reis , Rabiner Eugenii A. , Gunn Roger N. , Vernon Anthony C. , Natesan Sridhar , Howes Oliver D. 
Published: July 2021

AbstractGlutamatergic excitotoxicity is hypothesised to underlie synaptic loss in schizophrenia pathogenesis, but it is unknown whether synaptic markers are related to glutamatergic function in vivo. Additionally, it has been proposed that N-acetyl aspartate (NAA) levels reflect neuronal integrity. Here, we investigated whether synaptic vesicle glycoprotein 2 A (SV2A) levels are related to glutamatergic markers and NAA in healthy volunteers (HV) and schizophrenia patients (SCZ). Forty volunteers (SCZ n = 18, HV n = 22) underwent [11C]UCB-J positron emission tomography and proton magnetic resonance spectroscopy (1H-MRS) imaging in the left hippocampus and anterior cingulate cortex (ACC) to index [11C]UCB-J distribution volume ratio (DVR), and creatine-scaled glutamate (Glu/Cr), glutamate and glutamine (Glx/Cr) and NAA (NAA/Cr). In healthy volunteers, but not patients, [11C]UCB-J DVR was significantly positively correlated with Glu/Cr, in both the hippocampus and ACC. Furthermore, in healthy volunteers, but not patients, [11C]UCB-J DVR was significantly positively correlated with Glx/Cr, in both the hippocampus and ACC. There were no significant relationships between [11C]UCB-J DVR and NAA/Cr in the hippocampus or ACC in healthy volunteers or patients. Therefore, an appreciable proportion of the brain 1H-MRS glutamatergic signal is related to synaptic density in healthy volunteers. This relationship is not seen in schizophrenia, which, taken with lower synaptic marker levels, is consistent with lower levels of glutamatergic terminals and/or a lower proportion of glutamatergic relative to GABAergic terminals in the ACC in schizophrenia.
Reduced cortical thickness of the paracentral lobule in at-risk mental state individuals with poor 1-year functional outcomes
Authors: Sasabayashi Daiki , Takayanagi Yoichiro , Takahashi Tsutomu , Nishiyama Shimako , Mizukami Yuko , Katagiri Naoyuki , Tsujino Naohisa , Nemoto Takahiro , Sakuma Atsushi , Katsura Masahiro , Ohmuro Noriyuki , Okada Naohiro , Tada Mariko , Suga Motomu , Maikusa Norihide , Koike Shinsuke , Furuichi Atsushi , Kido Mikio , Noguchi Kyo , Yamasue Hidenori , Matsumoto Kazunori , Mizuno Masafumi , Kasai Kiyoto , Suzuki Michio 
Published: July 2021

AbstractAlthough widespread cortical thinning centered on the fronto-temporal regions in schizophrenia has been reported, the findings in at-risk mental state (ARMS) patients have been inconsistent. In addition, it remains unclear whether abnormalities of cortical thickness (CT) in ARMS individuals, if present, are related to their functional decline irrespective of future psychosis onset. In this multicenter study in Japan, T1-weighted magnetic resonance imaging was performed at baseline in 107 individuals with ARMS, who were subdivided into resilient (77, good functional outcome) and non-resilient (13, poor functional outcome) groups based on the change in Global Assessment of Functioning scores during 1-year follow-up, and 104 age- and sex-matched healthy controls recruited at four scanning sites. We measured the CT of the entire cortex and performed group comparisons using FreeSurfer software. The relationship between the CT and cognitive functioning was examined in an ARMS subsample (n = 70). ARMS individuals as a whole relative to healthy controls exhibited a significantly reduced CT, predominantly in the fronto-temporal regions, which was partly associated with cognitive impairments, and an increased CT in the left parietal and right occipital regions. Compared with resilient ARMS individuals, non-resilient ARMS individuals exhibited a significantly reduced CT of the right paracentral lobule. These findings suggest that ARMS individuals partly share CT abnormalities with patients with overt schizophrenia, potentially representing general vulnerability to psychopathology, and also support the role of cortical thinning in the paracentral lobule as a predictive biomarker for short-term functional decline in the ARMS population.
IRF-8/miR-451a regulates M-MDSC differentiation via the AMPK/mTOR signal pathway during lupus development
Authors: Shi Guoping , Li Dan , Zhang Dongya , Xu Yujun , Pan Yuchen , Lu Li , Li Jingman , Xia Xiaoyu , Dou Huan , Hou Yayi 
Published: July 2021

AbstractSystemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease. Myeloid-derived suppressor cells (MDSCs) have been found to be involved in the regulation of SLE development. However, little is known about the association between MDSC subsets and the factors that draw MDSCs into abnormal expansion. This study found that the percentage of M-MDSCs increased in mice with pristane-induced lupus. Toll-like receptor (TLR)7 signal activation and high interferon-α (IFN-α) level promoted M-MDSC differentiation in vitro. Moreover, both AMP-activated protein kinase (AMPK) agonist metformin and two mammalian targets of rapamycin (mTOR) inhibitors (INK128 and rapamycin) inhibited the percentage of M-MDSCs in lupus mice as well as in the TLR7- and IFN-α-induced bone marrow (BM) differentiation into MDSCs in vitro. In terms of mechanism, whole-genome transcriptome profiling was performed by RNA sequencing, revealing that the expression of the transcription factor IRF-8 was higher in M-MDSCs isolated from pristane-induced lupus mice, compared with control mice. IRF-8 was identified to be crucial for TLR7- and IFN-α-induced BM differentiation into MDSCs in vitro. Furthermore, interferon (IFN) regulatory factor8 (IRF-8) was targeted by miR-451a in M-MDSC differentiation. Of note, metformin-modified M-MDSCs could relieve lupus symptoms in pristane-induced lupus mice. The findings revealed a novel mechanism linking IRF-8/miR-451a to M-MDSC differentiation via the AMPK/mTOR signal pathway during lupus development. This study might provide an important reference for SLE therapy by targeting M-MDSCs.
Development of a fixed module repertoire for the analysis and interpretation of blood transcriptome data
Authors: Altman Matthew C. , Rinchai Darawan , Baldwin Nicole , Toufiq Mohammed , Whalen Elizabeth , Garand Mathieu , Syed Ahamed Kabeer Basirudeen , Alfaki Mohamed , Presnell Scott R. , Khaenam Prasong , Ayllón-Benítez Aaron , Mougin Fleur , Thébault Patricia , Chiche Laurent , Jourde-Chiche Noemie , Phillips J. Theodore , Klintmalm Goran , O’Garra Anne , Berry Matthew , Bloom Chloe , Wilkinson Robert J. , Graham Christine M. , Lipman Marc , Lertmemongkolchai Ganjana , Bedognetti Davide , Thiebaut Rodolphe , Kheradmand Farrah , Mejias Asuncion , Ramilo Octavio , Palucka Karolina , Pascual Virginia , Banchereau Jacques , Chaussabel Damien 
Published: July 2021

AbstractAs the capacity for generating large-scale molecular profiling data continues to grow, the ability to extract meaningful biological knowledge from it remains a limitation. Here, we describe the development of a new fixed repertoire of transcriptional modules, BloodGen3, that is designed to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome data. The construction of this repertoire is based on co-clustering patterns observed across sixteen immunological and physiological states encompassing 985 blood transcriptome profiles. Interpretation is supported by customized resources, including module-level analysis workflows, fingerprint grid plot visualizations, interactive web applications and an extensive annotation framework comprising functional profiling reports and reference transcriptional profiles. Taken together, this well-characterized and well-supported transcriptional module repertoire can be employed for the interpretation and benchmarking of blood transcriptome profiles within and across patient cohorts. Blood transcriptome fingerprints for the 16 reference cohorts can be accessed interactively via: https://drinchai.shinyapps.io/BloodGen3Module/.
Myofibroblast transcriptome indicates SFRP2hi fibroblast progenitors in systemic sclerosis skin
Authors: Tabib Tracy , Huang Mengqi , Morse Nina , Papazoglou Anna , Behera Rithika , Jia Minxue , Bulik Melissa , Monier Daisy E. , Benos Panayiotis V. , Chen Wei , Domsic Robyn , Lafyatis Robert 
Published: July 2021

AbstractSkin and lung fibrosis in systemic sclerosis (SSc) is driven by myofibroblasts, alpha-smooth muscle actin expressing cells. The number of myofibroblasts in SSc skin correlates with the modified Rodnan skin score, the most widely used clinical measure of skin disease severity. Murine fibrosis models indicate that myofibroblasts can arise from a variety of different cell types, but their origin in SSc skin has remained uncertain. Utilizing single cell RNA-sequencing, we define different dermal fibroblast populations and transcriptome changes, comparing SSc to healthy dermal fibroblasts. Here, we show that SSc dermal myofibroblasts arise in two steps from an SFRP2hi/DPP4-expressing progenitor fibroblast population. In the first step, SSc fibroblasts show globally upregulated expression of transcriptome markers, such as PRSS23 and THBS1. A subset of these cells shows markers indicating that they are proliferating. Only a fraction of SFRP2hi SSc fibroblasts differentiate into myofibroblasts, as shown by expression of additional markers, SFRP4 and FNDC1. Bioinformatics analysis of the SSc fibroblast transcriptomes implicated upstream transcription factors, including FOSL2, RUNX1, STAT1, FOXP1, IRF7 and CREB3L1, as well as SMAD3, driving SSc myofibroblast differentiation.
The effect of water on colloidal quantum dot solar cells
Authors: Shi Guozheng , Wang Haibin , Zhang Yaohong , Cheng Chen , Zhai Tianshu , Chen Botong , Liu Xinyi , Jono Ryota , Mao Xinnan , Liu Yang , Zhang Xuliang , Ling Xufeng , Zhang Yannan , Meng Xing , Chen Yifan , Duhm Steffen , Zhang Liang , Li Tao , Wang Lu , Xiong Shiyun , Sagawa Takashi , Kubo Takaya , Segawa Hiroshi , Shen Qing , Liu Zeke , Ma Wanli 
Published: July 2021

AbstractAlmost all surfaces sensitive to the ambient environment are covered by water, whereas the impacts of water on surface-dominated colloidal quantum dot (CQD) semiconductor electronics have rarely been explored. Here, strongly hydrogen-bonded water on hydroxylated lead sulfide (PbS) CQD is identified. The water could pilot the thermally induced evolution of surface chemical environment, which significantly influences the nanostructures, carrier dynamics, and trap behaviors in CQD solar cells. The aggravation of surface hydroxylation and water adsorption triggers epitaxial CQD fusion during device fabrication under humid ambient, giving rise to the inter-band traps and deficiency in solar cells. To address this problem, meniscus-guided-coating technique is introduced to achieve dense-packed CQD solids and extrude ambient water, improving device performance and thermal stability. Our works not only elucidate the water involved PbS CQD surface chemistry, but may also achieve a comprehensive understanding of the impact of ambient water on CQD based electronics.
SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’
Authors: Dorigatti Ilaria , Lavezzo Enrico , Manuto Laura , Ciavarella Constanze , Pacenti Monia , Boldrin Caterina , Cattai Margherita , Saluzzo Francesca , Franchin Elisa , Del Vecchio Claudia , Caldart Federico , Castelli Gioele , Nicoletti Michele , Nieddu Eleonora , Salvadoretti Elisa , Labella Beatrice , Fava Ludovico , Guglielmo Simone , Fascina Mariateresa , Grazioli Marco , Alvisi Gualtiero , Vanuzzo Maria Cristina , Zupo Tiziano , Calandrin Reginetta , Lisi Vittoria , Rossi Lucia , Castagliuolo Ignazio , Merigliano Stefano , Unwin H. Juliette T. , Plebani Mario , Padoan Andrea , Brazzale Alessandra R. , Toppo Stefano , Ferguson Neil M. , Donnelly Christl A. , Crisanti Andrea 
Published: July 2021

AbstractIn February and March 2020, two mass swab testing campaigns were conducted in Vo’, Italy. In May 2020, we tested 86% of the Vo’ population with three immuno-assays detecting antibodies against the spike and nucleocapsid antigens, a neutralisation assay and Polymerase Chain Reaction (PCR). Subjects testing positive to PCR in February/March or a serological assay in May were tested again in November. Here we report on the results of the analysis of the May and November surveys. We estimate a seroprevalence of 3.5% (95% Credible Interval (CrI): 2.8–4.3%) in May. In November, 98.8% (95% Confidence Interval (CI): 93.7–100.0%) of sera which tested positive in May still reacted against at least one antigen; 18.6% (95% CI: 11.0–28.5%) showed an increase of antibody or neutralisation reactivity from May. Analysis of the serostatus of the members of 1,118 households indicates a 26.0% (95% CrI: 17.2–36.9%) Susceptible-Infectious Transmission Probability. Contact tracing had limited impact on epidemic suppression.
Structures of ABCG2 under turnover conditions reveal a key step in the drug transport mechanism
Authors: Yu Qin , Ni Dongchun , Kowal Julia , Manolaridis Ioannis , Jackson Scott M. , Stahlberg Henning , Locher Kaspar P. 
Published: July 2021

AbstractABCG2 is a multidrug transporter that affects drug pharmacokinetics and contributes to multidrug resistance of cancer cells. In previously reported structures, the reaction cycle was halted by the absence of substrates or ATP, mutation of catalytic residues, or the presence of small-molecule inhibitors or inhibitory antibodies. Here we present cryo-EM structures of ABCG2 under turnover conditions containing either the endogenous substrate estrone-3-sulfate or the exogenous substrate topotecan. We find two distinct conformational states in which both the transport substrates and ATP are bound. Whereas the state turnover-1 features more widely separated NBDs and an accessible substrate cavity between the TMDs, turnover-2 features semi-closed NBDs and an almost fully occluded substrate cavity. Substrate size appears to control which turnover state is mainly populated. The conformational changes between turnover-1 and turnover-2 states reveal how ATP binding is linked to the closing of the cytoplasmic side of the TMDs. The transition from turnover-1 to turnover-2 is the likely bottleneck or rate-limiting step of the reaction cycle, where the discrimination of substrates and inhibitors occurs.
Elimination of noise in optically rephased photon echoes
Authors: Ma You-Zhi , Jin Ming , Chen Duo-Lun , Zhou Zong-Quan , Li Chuan-Feng , Guo Guang-Can 
Published: July 2021

AbstractPhoton echo is a fundamental tool for the manipulation of electromagnetic fields. Unavoidable spontaneous emission noise is generated in this process due to the strong rephasing pulse, which limits the achievable signal-to-noise ratio and represents a fundamental obstacle towards their applications in the quantum regime. Here we propose a noiseless photon-echo protocol based on a four-level atomic system. We implement this protocol in a Eu3+:Y2SiO5 crystal to serve as an optical quantum memory. A storage fidelity of 0.952 ± 0.018 is obtained for time-bin qubits encoded with single-photon-level coherent pulses, which is far beyond the maximal fidelity achievable using the classical measure-and-prepare strategy. In this work, the demonstrated noiseless photon-echo quantum memory features spin-wave storage, easy operation and high storage fidelity, which should be easily extended to other physical systems.