scholarly journals The Drosophila pioneer factor Zelda modulates the nuclear microenvironment of a Dorsal target enhancer to potentiate transcriptional output

2018 ◽  
Author(s):  
Shigehiro Yamada ◽  
Peter H. Whitney ◽  
Shao-Kuei Huang ◽  
Elizabeth C. Eck ◽  
Hernan G. Garcia ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Target Gene ◽  
Rate Increase ◽  
Imaging System ◽  
Effective Rate ◽  
Model System ◽  
Developmental Patterning ◽  
Pioneer Factor ◽  
Transcriptional Output

SummaryConnecting the developmental patterning of tissues to the mechanistic control of RNA polymerase II remains a long term goal of developmental biology. Many key elements have been identified in the establishment of spatial-temporal control of transcription in the early Drosophila embryo, a model system for transcriptional regulation. The dorsal/ventral axis of the Drosophila embryo is determined by the graded distribution of Dorsal (DL), a homologue of the NF-κB family of transcriptional activators found in humans [1,2]. A second maternally deposited factor, Zelda (ZLD), is uniformly distributed in the embryo and is thought to act as a pioneer factor, increasing enhancer accessibility for transcription factors such as DL [3–9]. Here we utilized the MS2 live imaging system to evaluate the expression of the DL target gene short gastrulation (sog) to better understand how a pioneer factor affects the kinetic parameters of transcription. Our experiments indicate that ZLD modifies probability of activation, the timing of this activation, and the rate at which transcription occurs. Our results further show that this effective rate increase is due to an increased accumulation of DL at the site of transcription, suggesting that transcription factor “hubs” induced by ZLD [10] functionally regulate transcription.

scholarly journals Fuke Qianjin Combined with Antibiotic Therapy for Pelvic Inflammatory Disease: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yu Chen ◽  
Shaobin Wei ◽  
Li Huang ◽  
Mei Luo ◽  
Yang Wu ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Pelvic Inflammatory Disease ◽  
Inflammatory Disease ◽  
Meta Analysis ◽  
Lower Abdominal Pain ◽  
Effective Rate ◽  
Chinese Patent ◽  
Meta Analyses

Background. Pelvic inflammatory disease (PID) without timely and proper treatment can cause long-term sequelae; meanwhile, patients will be confronted with the antimicrobial resistance and side effects. Chinese patent medicine as a supplement is used to treat PID with satisfactory clinical efficacy. This study evaluated the efficacy and safety of Fuke Qianjin (FKQJ) combined with antibiotics in the treatment of PID. Methods. Eight electronic databases and other resources were searched to make a collection of the randomized controlled trials (RCTs) from 1990 to 2019. The RCTs contrasting the effect of FKQJ combined with antibiotics regimens and antibiotics alone in reproductive women with PID were included. The antibiotics regimens are all recommended by the guidelines. Two reviewers independently screened the studies, extracted the data, and assessed the methodological quality of the included studies. Then, the meta-analyses were performed by RevMan 5. 3 software if appropriate. Results. Twenty-three RCTs (2527 women) were included in this review. The evidence showed that FKQJ combined with antibiotics improved the markedly effective rate compared to antibiotics alone group (RR = 1.38, 95% CI 1.27 to 1.49, I2 = 42%), shortened the improvement time of low abdominal pain (MD = −1.11, 95% CI −1.39 to −0.84, I2 = 38%), and increased the rate of lower abdominal pain improvement (RR = 1.35, 95% CI 1.19 to 1.55, I2 = 0). The implementation of adjuvant reduced the recurrent rate compared with antibiotics alone (RR = 0.27, 95% CI 0.13 to 0.56, I2 = 0%). Conclusions. Based on available evidence, FKQJ combined with antibiotics therapy have certain outcomes on increasing the markedly effective rate, decreasing the recurrent rate compared with antibiotics alone group. This therapy appears to improve lower abdominal pain and curtail the relief time. Due to the low quality and the risk of bias, any high-quality evidence or longer follow-up period should be advisable and necessary in the future.

scholarly journals The Long-Term Effective Rate of Different Branches of Idiopathic Trigeminal Neuralgia After Single Radiofrequency Thermocoagulation

Medicine ◽  
2015 ◽  
Vol 94 (45) ◽  
pp. e1994 ◽  
Author(s):  
Yuan-Zhang Tang ◽  
Bai-Shan Wu ◽  
Li-Qiang Yang ◽  
Jian-Ning Yue ◽  
Liang-Liang He ◽  
...  
Keyword(s):  
Trigeminal Neuralgia ◽  
Effective Rate ◽  
Radiofrequency Thermocoagulation ◽  
Idiopathic Trigeminal Neuralgia

scholarly journals Multiciliated cell basal bodies align in stereotypical patterns coordinated by the apical cytoskeleton

2016 ◽  
Vol 214 (5) ◽  
pp. 571-586 ◽  
Author(s):  
Elisa Herawati ◽  
Daisuke Taniguchi ◽  
Hatsuho Kanoh ◽  
Kazuhiro Tateishi ◽  
Shuji Ishihara ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Imaging System ◽  
Basal Bodies ◽  
Large Numbers ◽  
Multiciliated Cells ◽  
Alignment Process ◽  
Flow Through ◽  
Linear Alignment ◽  
Green Fluorescent

Multiciliated cells (MCCs) promote fluid flow through coordinated ciliary beating, which requires properly organized basal bodies (BBs). Airway MCCs have large numbers of BBs, which are uniformly oriented and, as we show here, align linearly. The mechanism for BB alignment is unexplored. To study this mechanism, we developed a long-term and high-resolution live-imaging system and used it to observe green fluorescent protein–centrin2–labeled BBs in cultured mouse tracheal MCCs. During MCC differentiation, the BB array adopted four stereotypical patterns, from a clustering “floret” pattern to the linear “alignment.” This alignment process was correlated with BB orientations, revealed by double immunostaining for BBs and their asymmetrically associated basal feet (BF). The BB alignment was disrupted by disturbing apical microtubules with nocodazole and by a BF-depleting Odf2 mutation. We constructed a theoretical model, which indicated that the apical cytoskeleton, acting like a viscoelastic fluid, provides a self-organizing mechanism in tracheal MCCs to align BBs linearly for mucociliary transport.

scholarly journals Moral Hazard and Claims Deterrence in Private Disability Insurance

2014 ◽  
Vol 6 (4) ◽  
pp. 110-141 ◽  
Author(s):  
David Autor ◽  
Mark Duggan ◽  
Jonathan Gruber
Keyword(s):  
Moral Hazard ◽  
Empirical Analysis ◽  
Time Variation ◽  
Rate Increase ◽  
Disability Insurance ◽  
Severe Disabilities ◽  
Replacement Rate ◽  
Waiting Period ◽  
Over Time

Exploiting within-firm, over-time variation in plan parameters for nearly 10,000 Long Term Disability (LTD) policies held by US employers, we present the first empirical analysis of the determinants of private LTD spells. We find that a shorter waiting period and a higher replacement rate increase the incidence of LTD spells. Sixty percent of the latter effect is due to the mechanical censoring of shorter spells, with the remainder due to the deterrence of spells that would have continued beyond the waiting period. Deterrence is driven primarily by a reduction in the incidence of shorter duration spells and less severe disabilities. (JEL D82, G22, J28, J32)

scholarly journals Bursted BMP Triggered Receptor Kinase Activity Drives Smad1 Mediated Long-Term Target Gene Oscillation in c2c12 Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (4) ◽  
pp. e59442 ◽  
Author(s):  
Daniela Schul ◽  
Alexandra Schmitt ◽  
Janine Regneri ◽  
Manfred Schartl ◽  
Toni Ulrich Wagner
Keyword(s):  
Target Gene ◽  
Kinase Activity ◽  
C2c12 Cells ◽  
Receptor Kinase

scholarly journals A Transcription Factor Pulse Can Prime Chromatin for Heritable Transcriptional Memory

2016 ◽  
Vol 37 (4) ◽  
Author(s):  
Aimee Iberg-Badeaux ◽  
Samuel Collombet ◽  
Benoit Laurent ◽  
Chris van Oevelen ◽  
Kuo-Kai Chin ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Rna Polymerase Ii ◽  
Target Genes ◽  
Short Term Memory ◽  
Epigenetic Mechanism ◽  
Short Term ◽  
Term Memory ◽  
Pol Ii ◽  
Transcriptional Memory

ABSTRACT Short-term and long-term transcriptional memory is the phenomenon whereby the kinetics or magnitude of gene induction is enhanced following a prior induction period. Short-term memory persists within one cell generation or in postmitotic cells, while long-term memory can survive multiple rounds of cell division. We have developed a tissue culture model to study the epigenetic basis for long-term transcriptional memory (LTTM) and subsequently used this model to better understand the epigenetic mechanisms that enable heritable memory of temporary stimuli. We find that a pulse of transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) induces LTTM on a subset of target genes that survives nine cell divisions. The chromatin landscape at genes that acquire LTTM is more repressed than at those genes that do not exhibit memory, akin to a latent state. We show through chromatin immunoprecipitation (ChIP) and chemical inhibitor studies that RNA polymerase II (Pol II) elongation is important for establishing memory in this model but that Pol II itself is not retained as part of the memory mechanism. More generally, our work reveals that a transcription factor involved in lineage specification can induce LTTM and that failure to rerepress chromatin is one epigenetic mechanism underlying transcriptional memory.

scholarly journals The Drosophila Pioneer Factor Zelda Modulates the Nuclear Microenvironment of a Dorsal Target Enhancer to Potentiate Transcriptional Output

2019 ◽  
Vol 29 (8) ◽  
pp. 1387-1393.e5 ◽  
Author(s):  
Shigehiro Yamada ◽  
Peter H. Whitney ◽  
Shao-Kuei Huang ◽  
Elizabeth C. Eck ◽  
Hernan G. Garcia ◽  
...  
Keyword(s):  
Pioneer Factor ◽  
Transcriptional Output

An Examination of Follow-up Services Received by Vulnerable Burn Populations: A Burn Model System National Database Study

2019 ◽  
Vol 41 (2) ◽  
pp. 377-383
Author(s):  
Lynne Benavides ◽  
Vivian Shie ◽  
Brennan Yee ◽  
Miranda Yelvington ◽  
Laura C Simko ◽  
...  
Keyword(s):  
Vulnerable Populations ◽  
Long Term Care ◽  
Model System ◽  
Psychological Therapy ◽  
Psychological Services ◽  
National Database ◽  
Vulnerable Group ◽  
Term Care

Abstract While disparities in healthcare outcomes and services for vulnerable populations have been documented, the extent to which vulnerable burn populations demonstrate disparities in long-term care is relatively underexplored. This study’s goal was to assess for differences in long-term occupational or physical therapy (OT/PT) and psychological service use after burn injury in vulnerable populations. Data from the Burn Model System National Database (2006–2015) were analyzed. The vulnerable group included participants in one or more of these categories: 65 years of age or older, nonwhite, no insurance or Medicaid insurance, preinjury receipt of psychological therapy or counseling, preinjury alcohol and/or drug misuse, or with a preexisting disability. Primary outcomes investigated were receipt of OT/PT and psychological services. Secondary outcomes included nine OT/PT subcategories. Outcomes were examined at 6, 12, and 24 months postinjury. One thousand one hundred thirty-six burn survivors (692 vulnerable; 444 nonvulnerable) were included. The vulnerable group was mostly female, unemployed at time of injury, and with smaller burns. Both groups received similar OT/PT and psychological services at all time points. Adjusted regression analyses found that while the groups received similar amounts services, some vulnerable subgroups received significantly more services. Participants 65 years of age or older, who received psychological therapy or counseling prior to injury, and with a preexisting disability received more OT/PT and psychological or peer support services at follow-up. Overall, vulnerable and nonvulnerable groups received comparable OT/PT and psychological services. The importance of long-term care among vulnerable subgroups of the burn population is highlighted by this study. Future work is needed to determine adequate levels of follow-up services.

6 NOVEL BRD4 INHIBITORS BLOCK THE PATHOLOGICAL ACTIVATION OF BRD4-NFκB SIGNALING AND SUPPRESS COLONIC INFLAMMATION IN IBD MOUSE MODELS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S7-S7
Author(s):  
Zhiqing Liu ◽  
Gabriela Uribe ◽  
Yi Li ◽  
Wang Pingyuan ◽  
Haiying Chen ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Critical Role ◽  
Neoplastic Transformation ◽  
Mucosal Inflammation ◽  
Gene Expressions ◽  
Colon Tissue ◽  
Colonic Inflammation ◽  
Brd4 Inhibition

Abstract Ulcerative Colitis (UC) and Crohn’s Disease (CD) are two major types of inflammatory bowel disease (IBD), with recurrent symptoms and significant morbidity. Long-term persistence of chronic inflammation in IBD is among the major factors contributing to neoplastic transformation and development of colitis-associated colorectal cancer. There is a lack of efficient medications for IBD, due to either limited efficacy or side effects. Antibodies against TNFα are effective therapies; however, they are expensive, and up to 40% of patients are non-responders. Thus, improved therapy with higher efficacy, enhanced safety and better patient affordability is urgently needed. The master regulator of innate immune response NFκB plays a critical role in the initiation and chronicity of IBD mucosal inflammation. We demonstrated that bromodomain-containing protein 4 (BRD4), an epigenetic reader, is required for stabilization of NFκB binding on the promoters of inflammatory genes, activation of RNA polymerase II, and histone H3 Lys122 acetylation (H3K122ac) to permit high levels of inflammatory gene expressions by sentinel epithelial cells and stromal fibroblasts. Our data using human IBD patient samples suggest that BRD4 activation is critical to the initiation of colonic inflammation. We have successfully identified highly potent and specific BRD4 inhibitors, demonstrating that inhibition of BRD4 suppresses expression of inflammatory cytokines TNFα, IL-6, IL-17A, and IL-8. Administration of our lead inhibitors (ZL0454 & ZL0420) significantly reduces initiation of the mucosal inflammation in both dextran sulfate sodium (DSS)-induced and Cbir1 T cell transfer colitis models in vivo, but with low toxicity and much safer than the generic NFκB/IKK inhibitor BMS345541. The levels of NFkB and BRD4 activation were also compared using immunofluorescence staining of NFkB/RelA translocation, phospho-Ser276 RelA formation, and induction of the BRD4 marker H3K122Ac. The BRD4 inhibitors reduced DSS-induced NFkB-BRD4 activation in colon tissue, demonstrating the target specificity in vivo. Our data suggest that BRD4 activation is critical to the initiation of the colonic inflammation during IBD. BRD4 inhibition disrupts its interactions with acetylated histone lysine residues, thereby blocking the pathological activation of the BRD4-NFκB signaling and suppressing colonic inflammation. Therefore, inhibition of the BRD4 activation is an attractive target for the development of novel IBD therapy and in prevention of CAC. Using our novel BRD4 inhibitors, we will further seek to evaluate the effect of long-term BRD4 inhibition on UC-induced neoplastic transformation and development of CAC. Funding support: Crohn’s & Colitis Foundation Entrepreneurial Investing (EI) Initiative award and a research fellowship award from the Crohn’s & Colitis Foundation of America.

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