bluuebunny/crossref_metadata_2025_split huggingface dataset:
RS3PE syndrome: Autoinflammatory features of a rare disorder
Authors: Borges Tiago , Silva Sérgio 
Published: July 2022

ABSTRACT
Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome was first described by McCarty in 1985 and is characterized by pitting oedema and an acute symmetrical synovitis of small joints. Self-directed inflammation in autoimmune disorders is caused by an abnormal activation of the adaptive immune system, while in autoinflammatory disorders, it is due to aberrant activation of the innate immune system without autoantibodies or autoreactive T cells. The role of autoimmunity in the pathogenesis of RS3PE syndrome is suggested by possible associations with some autoimmune diseases and human leukocyte antigen (HLA) haplotypes. However, several other features point to a possible role of autoinflammation in RS3PE syndrome. In this review, the relative contributions of both innate and adaptive immune systems to the pathogenesis of RS3PE syndrome are discussed.
MPP6 stimulates both RRP6 and DIS3 to degrade a specified subset of MTR4-sensitive substrates in the human nucleus
Authors: Fujiwara Naoko , Shigemoto Maki , Hirayama Mizuki , Fujita Ken-ichi , Seno Shigeto , Matsuda Hideo , Nagahama Masami , Masuda Seiji 
Published: July 2022

Abstract
Recent in vitro reconstitution analyses have proven that the physical interaction between the exosome core and MTR4 helicase, which promotes the exosome activity, is maintained by either MPP6 or RRP6. However, knowledge regarding the function of MPP6 with respect to in vivo exosome activity remains scarce. Here, we demonstrate a facilitative function of MPP6 that composes a specific part of MTR4-dependent substrate decay by the human exosome. Using RNA polymerase II-transcribed poly(A)+ substrate accumulation as an indicator of a perturbed exosome, we found functional redundancy between RRP6 and MPP6 in the decay of these poly(A)+ transcripts. MTR4 binding to the exosome core via MPP6 was essential for MPP6 to exert its redundancy with RRP6. However, at least for the decay of our identified exosome substrates, MTR4 recruitment by MPP6 was not functionally equivalent to recruitment by RRP6. Genome-wide classification of substrates based on their sensitivity to each exosome component revealed that MPP6 deals with a specific range of substrates and highlights the importance of MTR4 for their decay. Considering recent findings of competitive binding to the exosome between auxiliary complexes, our results suggest that the MPP6-incorporated MTR4-exosome complex is one of the multiple alternative complexes rather than the prevailing one.
Structural assembly of the nucleic-acid-binding Thp3–Csn12–Sem1 complex functioning in mRNA splicing
Authors: Kuang Zhiling , Ke Jiyuan , Hong Jiong , Zhu Zhongliang , Niu Liwen 
Published: July 2022

Abstract
PCI domain proteins play important roles in post-transcriptional gene regulation. In the TREX-2 complex, PCI domain-containing Sac3 and Thp1 proteins and accessory Sem1 protein form a ternary complex required for mRNA nuclear export. In contrast, structurally related Thp3–Csn12–Sem1 complex mediates pre-mRNA splicing. In this study, we determined the structure of yeast Thp3186–470–Csn12–Sem1 ternary complex at 2.9 Å resolution. Both Thp3 and Csn12 structures have a typical PCI structural fold, characterized by a stack of α-helices capped by a C-terminal winged-helix (WH) domain. The overall structure of Thp3186–470–Csn12–Sem1 complex has an inverted V-shape with Thp3 and Csn12 forming the two sides. A fishhook-shaped Sem1 makes extensive contacts on Csn12 to stabilize its conformation. The overall structure of Thp3186–470–Csn12–Sem1 complex resembles the previously reported Sac3–Thp1–Sem1 complex, but also has significant structural differences. The C-terminal WH domains of Thp3 and Csn12 form a continuous surface to bind different forms of nucleic acids with micromolar affinity. Mutation of the basic residues in the WH domains of Thp3 and Csn12 affects nucleic acid binding in vitro and mRNA splicing in vivo. The Thp3–Csn12–Sem1 structure provides a foundation for further exploring the structural elements required for its specific recruitment to spliceosome for pre-mRNA splicing.
TET1 regulates gene expression and repression of endogenous retroviruses independent of DNA demethylation
Authors: Stolz Paul , Mantero Angelo Salazar , Tvardovskiy Andrey , Ugur Enes , Wange Lucas E , Mulholland Christopher B , Cheng Yuying , Wierer Michael , Enard Wolfgang , Schneider Robert , Bartke Till , Leonhardt Heinrich , Elsässer Simon J , Bultmann Sebastian 
Published: July 2022

Abstract
DNA methylation (5-methylcytosine (5mC)) is critical for genome stability and transcriptional regulation in mammals. The discovery that ten-eleven translocation (TET) proteins catalyze the oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) revolutionized our perspective on the complexity and regulation of DNA modifications. However, to what extent the regulatory functions of TET1 can be attributed to its catalytic activity remains unclear. Here, we use genome engineering and quantitative multi-omics approaches to dissect the precise catalytic vs. non-catalytic functions of TET1 in murine embryonic stem cells (mESCs). Our study identifies TET1 as an essential interaction hub for multiple chromatin modifying complexes and a global regulator of histone modifications. Strikingly, we find that the majority of transcriptional regulation depends on non-catalytic functions of TET1. In particular, we show that TET1 is critical for the establishment of H3K9me3 and H4K20me3 at endogenous retroviral elements (ERVs) and their silencing that is independent of its canonical role in DNA demethylation. Furthermore, we provide evidence that this repression of ERVs depends on the interaction between TET1 and SIN3A. In summary, we demonstrate that the non-catalytic functions of TET1 are critical for regulation of gene expression and the silencing of endogenous retroviruses in mESCs.
FACT subunit SUPT16H associates with BRD4 and contributes to silencing of interferon signaling
Authors: Zhou Dawei , Wu Zhenyu , Park Jun-Gyu , Fiches Guillaume N , Li Tai-Wei , Ma Qin , Huang Huachao , Biswas Ayan , Martinez-Sobrido Luis , Santoso Netty G , Zhu Jian 
Published: July 2022

Abstract
FACT (FAcilitates Chromatin Transcription) is a heterodimeric protein complex composed of SUPT16H and SSRP1, and a histone chaperone participating in chromatin remodeling during gene transcription. FACT complex is profoundly regulated, and contributes to both gene activation and suppression. Here we reported that SUPT16H, a subunit of FACT, is acetylated in both epithelial and natural killer (NK) cells. The histone acetyltransferase TIP60 contributes to the acetylation of SUPT16H middle domain (MD) at lysine 674 (K674). Such acetylation of SUPT16H is recognized by bromodomain protein BRD4, which promotes protein stability of SUPT16H in both epithelial and NK cells. We further demonstrated that SUPT16H-BRD4 associates with histone modification enzymes (HDAC1, EZH2), and further regulates their activation status and/or promoter association as well as affects the relevant histone marks (H3ac, H3K9me3 and H3K27me3). BRD4 is known to profoundly regulate interferon (IFN) signaling, while such function of SUPT16H has never been explored. Surprisingly, our results revealed that SUPT16H genetic knockdown via RNAi or pharmacological inhibition by using its inhibitor, curaxin 137 (CBL0137), results in the induction of IFNs and interferon-stimulated genes (ISGs). Through this mechanism, depletion or inhibition of SUPT16H is shown to efficiently inhibit infection of multiple viruses, including Zika, influenza, and SARS-CoV-2. Furthermore, we demonstrated that depletion or inhibition of SUPT16H also causes the remarkable activation of IFN signaling in NK cells, which promotes the NK-mediated killing of virus-infected cells in a co-culture system using human primary NK cells. Overall, our studies unraveled the previously un-appreciated role of FACT complex in coordinating with BRD4 and regulating IFN signaling in both epithelial and NK cells, and also proposed the novel application of the FACT inhibitor CBL0137 to treat viral infections.
sRNA-controlled iron sparing response in Staphylococci
Authors: Coronel-Tellez Rodrigo H , Pospiech Mateusz , Barrault Maxime , Liu Wenfeng , Bordeau Valérie , Vasnier Christelle , Felden Brice , Sargueil Bruno , Bouloc Philippe 
Published: July 2022

Abstract
Staphylococcus aureus, a human opportunist pathogen, adjusts its metabolism to cope with iron deprivation within the host. We investigated the potential role of small non-coding RNAs (sRNAs) in dictating this process. A single sRNA, named here IsrR, emerged from a competition assay with tagged-mutant libraries as being required during iron starvation. IsrR is iron-repressed and predicted to target mRNAs expressing iron-containing enzymes. Among them, we demonstrated that IsrR down-regulates the translation of mRNAs of enzymes that catalyze anaerobic nitrate respiration. The IsrR sequence reveals three single-stranded C-rich regions (CRRs). Mutational and structural analysis indicated a differential contribution of these CRRs according to targets. We also report that IsrR is required for full lethality of S. aureus in a mouse septicemia model, underscoring its role as a major contributor to the iron-sparing response for bacterial survival during infection. IsrR is conserved among staphylococci, but it is not ortholog to the proteobacterial sRNA RyhB, nor to other characterized sRNAs down-regulating mRNAs of iron-containing enzymes. Remarkably, these distinct sRNAs regulate common targets, illustrating that RNA-based regulation provides optimal evolutionary solutions to improve bacterial fitness when iron is scarce.
Stochastically multimerized ParB orchestrates DNA assembly as unveiled by single-molecule analysis
Authors: Guo Lijuan , Zhao Yilin , Zhang Qian , Feng Ying , Bi Lulu , Zhang Xia , Wang Teng , Liu Cong , Ma Hanhui , Sun Bo 
Published: July 2022

Abstract
The tripartite ParABS system mediates chromosome segregation in a wide range of bacteria. Dimeric ParB was proposed to nucleate on parS sites and spread to neighboring DNA. However, how properly distributed ParB dimers further compact chromosomal DNA into a higher-order nucleoprotein complex for partitioning remains poorly understood. Here, using a single-molecule approach, we show that tens of Bacillus subtilis ParB (Spo0J) proteins can stochastically multimerize on and stably bind to nonspecific DNA. The introduction of CTP promotes the formation and diffusion of the multimeric ParB along DNA, offering an opportunity for ParB proteins to further forgather and cluster. Intriguingly, ParB multimers can recognize parS motifs and are more inclined to remain immobile on them. Importantly, the ParB multimer features distinct capabilities of not only bridging two independent DNA molecules but also mediating their transportation, both of which are enhanced by the presence of either CTP or parS in the DNA. These findings shed new light on ParB dynamics in self-multimerization and DNA organization and help to better comprehend the assembly of the ParB-DNA partition complex.
Single-cell analysis reveals an Angpt4-initiated EPDC-EC-CM cellular coordination cascade during heart regeneration
Authors: Wu Zekai , Shi Yuan , Cui Yueli , Xing Xin , Zhang Liya , Liu Da , Zhang Yutian , Dong Ji , Jin Li , Pang Meijun , Xiao Rui-Ping , Zhu Zuoyan , Xiong Jing-Wei , Tong Xiangjun , Zhang Yan , Wang Shiqiang , Tang Fuchou , Zhang Bo 
Published: July 2022

Abstract
Mammals exhibit limited heart regeneration ability, which can lead to heart failure after myocardial infarction. In contrast, zebrafish exhibit remarkable cardiac regeneration capacity. Several cell types and signaling pathways have been reported to participate in this process. However, a comprehensive analysis of how different cells and signals interact and coordinate to regulate cardiac regeneration is unavailable. We collected major cardiac cell types from zebrafish and performed high-precision single-cell transcriptome analyses during both development and post-injury regeneration. We revealed the cellular heterogeneity as well as the molecular progress of cardiomyocytes during these processes, and identified a subtype of atrial cardiomyocyte exhibiting a stem-like state which may transdifferentiate into ventricular cardiomyocytes during regeneration. Furthermore, we identified a regeneration-induced cell (RIC) population in the epicardium-derived cells (EPDC), and demonstrated Angiopoietin 4 (Angpt4) as a specific regulator of heart regeneration. angpt4 expression is specifically and transiently activated in RIC, which initiates a signaling cascade from EPDC to endocardium through the Tie2-MAPK pathway, and further induces activation of cathepsin K in cardiomyocytes through RA signaling. Loss of angpt4 leads to defects in scar tissue resolution and cardiomyocyte proliferation, while overexpression of angpt4 accelerates regeneration. Furthermore, we found that ANGPT4 could enhance proliferation of neonatal rat cardiomyocytes, and promote cardiac repair in mice after myocardial infarction, indicating that the function of Angpt4 is conserved in mammals. Our study provides a mechanistic understanding of heart regeneration at single-cell precision, identifies Angpt4 as a key regulator of cardiomyocyte proliferation and regeneration, and offers a novel therapeutic target for improved recovery after human heart injuries.
Treatment for Mild Chronic Hypertension During Pregnancy
Authors: Tita Alan T. , Szychowski Jeff M. , Boggess Kim , Dugoff Lorraine , Sibai Baha , Lawrence Kirsten , Hughes Brenna L. , Bell Joseph , Aagaard Kjersti , Edwards Rodney K. , Gibson Kelly , Haas David M. , Plante Lauren , Metz Torri , Casey Brian , Esplin Sean , Longo Sherri , Hoffman Matthew , Saade George R. , Hoppe Kara K. , Foroutan Janelle , Tuuli Methodius , Owens Michelle Y. , Simhan Hyagriv N. , Frey Heather , Rosen Todd , Palatnik Anna , Baker Susan , August Phyllis , Reddy Uma M. , Kinzler Wendy , Su Emily , Krishna Iris , Nguyen Nicki , Norton Mary E. , Skupski Daniel , El-Sayed Yasser Y. , Ogunyemi Dotum , Galis Zorina S. , Harper Lorie , Ambalavanan Namasivayam , Geller Nancy L. , Oparil Suzanne , Cutter Gary R. , Andrews William W. 
Published: July 2022

(Abstracted from N Engl J Med 2022;386:1781–1792)
Chronic hypertension develops in 2% of pregnancies in the United States. As this condition disproportionately affects Black women and is associated with 3 to 5 times the risk of placental abruption, preeclampsia, preterm birth (PTB), small-for-gestational-age (SGA) birthweight, and perinatal death, optimizing treatment is critical to possibly preventing these associated complications.
Health Disparities in Uterine Cancer: Report From the Uterine Cancer Evidence Review Conference
Authors: Whetstone Sara , Burke William , Sheth Sangini S. , Brooks Rebecca , Cavens Arjeme , Huber-Keener Kathryn , Scott Dana M. , Worly Brett , Chelmow David 
Published: July 2022

(Abstracted from Obstet Gynecol 2022;139:645–659)
The American College of Obstetricians and Gynecologists (ACOG) convened a panel of experts to develop evidence-based educational materials for clinicians on health disparities in the treatment, diagnosis, and outcomes for uterine cancer. Based on reviews of the literature, best practices, and guidelines, the panel identified substantive inequities and provided guidance for future research.
A comparison of the efficacy of dutasteride on reducing lower urinary tract symptoms among patients with small versus large benign prostatic hyperplasia
Authors: Shigehara Kazuyoshi , Kato Yuki , Kawaguchi Shohei , Izumi Kouji , Kadono Yoshifumi , Mizokami Atsushi 
Published: July 2022

Abstract

Background
Only a few reports have currently studied the efficacy of dutasteride in patients with small benign prostatic hyperplasia (BPH). We investigated the efficacy of dutasteride on reducing lower urinary tract symptoms among them.

Materials and methods
A total of 81 patients with BPH who completed 52weeks of 0.5?mg dutasteride treatment were enrolled. Each patient filled out the International Prostatic Symptom Score (IPSS) and overactive bladder symptom score (OABSS) at baseline and at the 6- and 12-month follow-up visits. Total testosterone, prostate-specific antigen, adenoma/prostate volume (PV), uroflowmetry analysis, and postvoid residual volume were evaluated at baseline and at the 12-month follow-up visit. The enrolled patients were divided into 2 groups according to PV at baseline. The groups were as follows: Group A (PV ≥ 30 mL) and Group B (PV < 30 mL).

Results
Groups A and B had mean PVs of 52.1 and 23.6 mL and mean IPSS scores of 16.7 and 14.4, respectively. Group A had significantly higher OABSS and prostate-specific antigen levels at baseline than Group B, while no significant differences in any other baseline characteristics was observed. After dutasteride treatment, adenoma volume and PV decreased significantly, while testosterone level showed a significant increase in both groups. Group A showed significant improvements in the total IPSS, voiding and storage subscore of the IPSS, OABSS, maximum flow rate, and postvoid residual volume. Group B, on the other hand, also showed significant improvements only in the total IPSS, voiding subscore of the IPSS, and maximum flow rate.

Conclusions
The present study suggests a possible beneficial effect of dutasteride treatment on the reduction of lower urinary tract symptoms in patients with small and large BPH. However, the effectiveness of dutasteride was limited compared to patients with large BPH (PV ≥ 30 mL).
The “ins and outs” of the magnetic ureteral stent: A novel innovation in Endourology
Authors: Damodaran Vishal , Els Brandon , Daras Efthimia , Kataka Tracy , Gulamali Sadiyabanu Safiq , Ntakana S’babalwe , Perera Marlon , Adam Ahmed 
Published: July 2022

Abstract

Background
Ureteral stents play a major role in maintaining ureteral patency. Various innovations are advocated in the design and subsequent removal of traditional double-J ureteral stents, such as the magnetic-end double-J ureteral stent (MEDJUS). This stent facilitates outpatient removal using a magnetic stent removal device. This systematic review was conducted to analyze the published role, efficacy, and outcomes of MEDJUS.

Materials and methods
After PROSPERO registration (CRD42021235739), an electronic database search (PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science) was performed on December 31, 2020. The search terms were as follows: “magnetic,” “ureteric,” “stent,” “double-J,” “urotech,” and “Black-Star.”

Results
Nine studies with a total of 685 patients were included in the systematic review. The total number of MEDJUS procedures used was 498 (73%) compared to the 187 (27%) traditional double-J stent method. Magnetic-end double-J ureteral stent extraction failure was reported in 8 cases (1.61%). Compared with traditional stents, MEDJUS showed a cost benefit in 5/5 studies. Better pain scores (during stent in situ) and (at stent removal) were observed in 2/3 and 3/4 of the studies, respectively.

Conclusions
Magnetic-end double-J ureteral stent may serve as a viable alternative to traditional double-J stents, offering cost and pain benefits with similar rates of complications. Magnetic-end double-J ureteral stent also offers relative ease of extraction and a reduced need for inpatient removal. This ambulatory stent removal technique has forged its use in modern urological practice.
How Risk Management During COVID-19 Influences Eldercare Personnel's Perceptions of Their Work Environment
Authors: Rueskov Poulsen Vivian , Juul Nilsson Charlotte , Balle Hansen Morten , Bredal Charlotte , Juul-Madsen Maria , Nabe-Nielsen Kirsten 
Published: July 2022

Objective
To investigate the association between workplace COVID-19 (coronavirus disease 2019) risk management and eldercare workers' perception of their social environment at work.

Methods
Cross-sectional questionnaire data from 952 participants were collected by the Danish labor union, FOA, and analyzed using multinomial logistic regression.

Results
Unclear guidelines, insecurity regarding organization of work, lack of attention to vulnerable employees, and lack of instruction in the use of personal protective equipment were associated with perceived negative changes in the social environment at work. Also, higher local incidence rates of SARS-CoV-2 infections were associated with a weaker sense of community (odds ratio, 1.18; 95% confidence interval, 1.04–1.36).

Conclusions
These findings indicate that risk management is important not only for prevention of infection but also for individual and workplace resilience toward external demands and health threats.
Physical Exertion Partially Mitigates Task-Switching Deficits From Sleep Loss
Authors: Stepan Michelle E. , Wilckens Kristine A. , Hostler David , Wallace Meredith L. , Franzen Peter L. 
Published: July 2022

Objective
The aim of the study is to investigate effects of physical exertion on cognitive deficits from sleep loss under conditions that mimic a firefighting scenario.

Methods
Twenty-four male participants completed a crossover study design with 3 conditions: total sleep deprivation, sleep disruption (three 60-minute awakenings), and rested control. Participants then completed 50 minutes of a physical exertion task involving treadmill exercise in a heated room while wearing firefighter protective clothing. Vigilant attention and task-switching performance were assessed pre– and post–sleep manipulation and pre– and post–physical exertion. Vigilant attention was also assessed mid–physical exertion.

Results
Total sleep deprivation and sleep disruption increased attentional lapses and task-switching RT. Total sleep deprivation additionally reduced task-switching accuracy. Performance after physical exertion improved only for task-switching RT after total sleep deprivation.

Conclusions
Physical exertion selectively mitigated task-switching RT deficits from the most severe sleep loss condition, total sleep deprivation.