Miracle-dz/UniFAR-FTUs huggingface dataset:
Pioneer factors and ATP‐dependent chromatin remodeling factors interact dynamically: A new perspective

Transcription factor (TF) signaling regulates gene transcription and requires a complex network of proteins. This network includes co‐activators, co‐repressors, multiple TFs, histone‐modifying complexes, and the basal transcription machinery. It has been widely appreciated that pioneer factors, such as FoxA1 and GATA1, play an important role in opening closed chromatin regions, thereby allowing binding of a secondary factor. In this review we will focus on a newly proposed model wherein multiple TFs, such as steroid receptors (SRs), can function in a pioneering role. This model, termed dynamic assisted loading, integrates data from widely divergent methodologies, including genome wide ChIP‐Seq, digital genomic footprinting, DHS‐Seq, live cell protein dynamics, and biochemical studies of ATP‐dependent remodeling complexes, to present a real time view of TF chromatin interactions. Under this view, many TFs can act as initiating factors for chromatin landscape programming. Furthermore, enhancer and promoter states are more accurately described as energy‐dependent, non‐equilibrium steady states.
Antipoaching standards in onshore hydrocarbon concessions drawn from a Central African case study

Unsustainable hunting outside protected areas is threatening tropical biodiversity worldwide and requires conservationists to engage increasingly in antipoaching activities. Following the example of ecocertified logging companies, we argue that other extractive industries managing large concessions should engage in antipoaching activities as part of their environmental management plans. Onshore hydrocarbon concessions should also adopt antipoaching protocols as a standard because they represent a biodiversity threat comparable to logging. We examined the spatiotemporal patterns of small‐ and large‐mammal poaching in an onshore oil concession in Gabon, Central Africa, with a Bayesian occupancy model based on signs of poaching collected from 2010 to 2015 on antipoaching patrols. Patrol locations were initially determined based on local intelligence and past patrol successes (adaptive management) and subsequently with a systematic sampling of the concession. We generated maps of poaching probability in the concession and determined the temporal trends of this threat over 5 years. The spatiotemporal patterns of large‐ and small‐mammal poaching differed throughout the concession, and likely these groups will need different management strategies. By elucidating the relationship between site‐specific sampling effort and detection probability, the Bayesian method allowed us to set goals for future antipoaching patrols. Our results indicate that a combination of systematic sampling and adaptive management data is necessary to infer spatiotemporal patterns with the statistical method we used. On the basis of our case study, we recommend hydrocarbon companies interested in implementing efficient antipoaching activities in their onshore concessions to lay the foundation of long‐needed industry standards by: adequately measuring antipoaching effort; mixing adaptive management and balanced sampling; setting goals for antipoaching effort; pairing patrols with large‐mammal monitoring; supporting antipoaching patrols across the landscape; restricting access to their concessions; performing random searches for bushmeat and mammal products at points of entry; controlling urban and agricultural expansion; supporting bushmeat alternatives; and supporting land‐use planning.
Assertive Community Treatment For People With Alcohol Dependence: A Pilot Randomized Controlled Trial

Abstract Aims A pilot randomized controlled trial (RCT) to assess the feasibility and potential efficacy of assertive community treatment (ACT) in adults with alcohol dependence. Methods Single blind, individually randomized, pilot RCT of 12 months of ACT plus treatment as usual (TAU) versus TAU alone in adults (age 18+ years) with alcohol dependence and a history of previous unsuccessful alcohol treatment attending specialist community alcohol treatment services. ACT aimed to actively engage participants for 12 months with assertive, regular, minimum weekly contact. ACT was combined with TAU. TAU comprised access to the full range of services provided by the community teams. Primary outcome is mean drinks per drinking day and percent days abstinent at 12 months follow up. Analysis of covariance was conducted using 80% confidence intervals, appropriate in the context of a pilot trial. Results A total of 94 participants were randomized, 45 in ACT and 49 in TAU. Follow-up was achieved with 98 and 88%, respectively at 12 months. Those in ACT had better treatment engagement, and were more often seen in their homes or local community than TAU participants. At 12 months the ACT group had more problems related to drinking and lower quality of life than TAU but no differences in drinking measures. The ACT group had a higher percentage of days abstinent but lower quality of life at 6 months. The ACT group had less unplanned healthcare use than TAU. Conclusions An trial of ACT was feasible to implement in an alcohol dependent treatment population. Trial registration ISRCTN22775534
Small Dense Low-Density Lipoprotein as Biomarker for Atherosclerotic Diseases

Low-density lipoprotein (LDL) plays a key role in the development and progression of atherosclerosis and cardiovascular disease. LDL consists of several subclasses of particles with different sizes and densities, including large buoyant (lb) and intermediate and small dense (sd) LDLs. It has been well documented that sdLDL has a greater atherogenic potential than that of other LDL subfractions and that sdLDL cholesterol (sdLDL-C) proportion is a better marker for prediction of cardiovascular disease than that of total LDL-C. Circulating sdLDL readily undergoes multiple atherogenic modifications in blood plasma, such as desialylation, glycation, and oxidation, that further increase its atherogenicity. Modified sdLDL is a potent inductor of inflammatory processes associated with cardiovascular disease. Several laboratory methods have been developed for separation of LDL subclasses, and the results obtained by different methods can not be directly compared in most cases. Recently, the development of homogeneous assays facilitated the LDL subfraction analysis making possible large clinical studies evaluating the significance of sdLDL in the development of cardiovascular disease. Further studies are needed to establish guidelines for sdLDL evaluation and correction in clinical practice.
Trait Performance Correlations across Life Stages under Environmental Stress Conditions in the Common Frog, Rana temporaria

If an organism's juvenile and adult life stages inhabit different environments, certain traits may need to be independently adapted to each environment. In many organisms, a move to a different environment during ontogeny is accompanied by metamorphosis. In such organisms phenotypic induction early in ontogeny can affect later phenotypes. In laboratory experiments we first investigated correlations between body morphology and the locomotor performance traits expressed in different life stages of the common frog, Rana temporaria: swimming speed and acceleration in tadpoles; and jump-distance in froglets. We then tested for correlations between these performances across life stages. We also subjected tadpoles to unchanging or decreasing water levels to explore whether decreasing water levels might induce any carry-over effects. Body morphology and performance were correlated in tadpoles; morphology and performance were correlated in froglets: hence body shape and morphology affect performance within each life stage. However, performance was decoupled across life stages, as there was no correlation between performance in tadpoles and performance in froglets. While size did not influence tadpole performance, it was correlated with performance of the metamorphosed froglets. Experiencing decreasing water levels accelerated development time, which resulted in smaller tadpoles and froglets, i.e., a carry-over effect. Interestingly, decreasing water levels positively affected the performance of tadpoles, but negatively affected froglet performance. Our results suggest that performance does not necessarily have to be correlated between life stages. However, froglet performance is size dependent and carried over from the tadpole stage, suggesting that some important size-dependent characters cannot be decoupled via metamorphosis.
Training Addiction Counselors to Deliver A Brief Psychoeducational Intervention for Chronic Pain among Patients in Opioid Agonist Treatment: A Pilot Investigation

Background Despite high rates of chronic pain among their patients, opioid agonist treatment (OAT) counselors report an absence of training to manage chronic pain. Methods A multidisciplinary team developed a tailored training for counselors to screen and address chronic pain via a brief psychosocial intervention, and implemented it with 52 addiction counselors. Data on knowledge (9 true-false items) as well as attitudes, interest, and perceived ability (scored on 5-point Likert-type scales) were collected from counselors before (pre-test), after (post-test) training, and after 6 months (follow-up). Results Pre-test knowledge scores varied considerably. Compared to pre-test, mean counselor knowledge scores increased significantly post-training and at follow-up (p's.<05). The training was associated with increases in positive attitudes toward the role of counselors in managing chronic pain, interest in assessing chronic pain, and counselor ability to assess as well as suggest appropriate interventions for pain (all p's <.05). Perceived ability to assess chronic pain and suggest appropriate treatment interventions were higher at follow-up than at pre-test (p's <.05). Conclusions Findings related to the initial evaluation of this training were promising, and future research is warranted to further examine the efficacy of training drug counselors on psychosocial interventions to manage chronic pain among OAT patients.
RNA-Seq Analysis of IL-1B and IL-36 Responses in Epidermal Keratinocytes Identifies a Shared MyD88-Dependent Gene Signature

IL-36 cytokines have recently emerged as mediators of inflammation in autoimmune conditions including psoriasis vulgaris (PsV) and generalized pustular psoriasis (GPP). This study used RNA-seq to profile the transcriptome of primary epidermal keratinocytes (KCs) treated with IL-1B, IL-36A, IL-36B, or IL-36G. We identified some early IL-1B-specific responses (8 h posttreatment), but nearly all late IL-1B responses were replicated by IL-36 cytokines (24 h posttreatment). Type I and II interferon genes exhibited time-dependent response patterns, with early induction (8 h) followed by no response or repression (24 h). Altogether, we identified 225 differentially expressed genes (DEGs) with shared responses to all 4 cytokines at both time points (8 and 24 h). These involved upregulation of ligands (IL1A, IL1B, and IL36G) and activating proteases (CTSS) but also upregulation of inhibitors such as IL1RN and IL36RN. Shared IL-1B/IL-36 DEGs overlapped significantly with genes altered in PsV and GPP skin lesions, as well as genes near GWAS loci linked to autoimmune and autoinflammatory diseases (e.g., PsV, psoriatic arthritis, inflammatory bowel disease, and primary biliary cholangitis). Inactivation of MyD88 adapter protein using CRISPR/Cas9 completely abolished expression responses of such DEGs to IL-1B and IL-36G stimulation. These results provide a global view of IL-1B and IL-36 expression responses in epidermal KCs with fine-scale characterization of time-dependent and cytokine-specific response patterns. Our findings support an important role for IL-1B and IL-36 in autoimmune or autoinflammatory conditions and show that MyD88 adaptor protein mediates shared IL-1B/IL-36 responses.
Integrin αVβ3 can substitute for collagen‐binding β1‐integrins in vivo to maintain a homeostatic interstitial fluid pressure

What is the central question of this study? Collagen‐binding β1‐integrins function physiologically in cellular control of dermal interstitial fluid pressure (PIF) in vivo and thereby participate in control of extravascular fluid volume. During anaphylaxis, simulated by injection of compound 48/80, integrin αVβ3 takes over this physiological function. Here we addressed the question whether integrin αVβ3 can replace collagen‐binding β1‐integrin to maintain a long‐term homeostatic PIF. What is the main finding and its importance? Mice lacking the collagen‐binding integrin α11β1 show a complex dermal phenotype with regard to the interstitial physiology apparent in the control of PIF. Notably dermal PIF is not lowered with compound 48/80 in these animals. Our present data imply that integrin αVβ3 is the likely candidate that has taken over the role of collagen‐binding β1‐integrins for maintaining a steady‐state homeostatic PIF. A better understanding of molecular processes involved in control of PIF is instrumental for establishing novel treatment regimens for control of oedema formation in anaphylaxis and septic shock.
Morphological Changes of Neurons on Self-Organized Honeycomb Patterned Films

微細加工技術によってさまざまなマイクロパターンを作製した基板上に細胞を培養することにより細胞の接着形態, 機能や増殖能を制御できることが検討されている. 筆者らは, 従来の微細加工技術に頼らずに, さまざまな希薄高分子混合溶液を高湿度の雰囲気下でキャストすることにより, 自己組織化によって規則的なハニカム構造と微細孔を有する多孔質フィルムが得られることを報告してきた. 本研究では, この生分解性高分子からなるハニカムパターンフィルム上に神経細胞を培養し, フィルムの微細孔の孔径変化に伴う神経細胞の接着形態や神経突起形成への影響を走査型電子顕微鏡, 共焦点レーザー顕微鏡によって神経細胞の接着形態を観察することで検討した. 平膜上では, 神経細胞は紡錘形の形態であり, 神経突起はランダムに伸展した. 一方, ハニカムパターンフィルム上の神経細胞は, フィルムの微細孔の孔径変化に伴い細胞の接着形態が変化し, 神経突起はパターンの幹に沿って伸展しネットワーク構造を形成した.
Zinc Transporter-8 Autoantibodies Improve Prediction of Type 1 Diabetes in Relatives Positive for the Standard Biochemical Autoantibodies

OBJECTIVE We assessed diabetes risk associated with zinc transporter-8 antibodies (ZnT8A), islet cell antibodies (ICA), and HLA type and age in relatives of people with type 1 diabetes with the standard biochemical autoantibodies (BAA) to insulin (IAA), GAD65 (GAD65A), and/or insulinoma-associated protein 2 antigen (IA-2A). RESEARCH DESIGN AND METHODS For this analysis, 2,256 relatives positive for at least one BAA, of whom 142 developed diabetes, were tested for ZnT8A, ICA, and HLA genotype followed by biannual oral glucose tolerance tests. ZnT8A were also tested in 911 randomly chosen antibody-negative relatives. RESULTS ZnT8A were associated with the other BAA (548 of 2,256 [24.3%] BAA+ vs. 8 of 911 [0.8%] BAA−, P < 0.001) and BAA number (177 of 1,683 [10.5%] single-, 221 of 384 [57.6%] double-, and 150 of 189 [79.4%] triple-BAA positivity, P < 0.001). The 4-year diabetes risk was higher in single BAA+ relatives with ZnT8A than ZnT8A− relatives (31 vs. 7%, P < 0.001). In multivariable analysis, age ≤20 years (hazard ratio 2.13, P = 0.03), IA-2A (2.15, P = 0.005), IAA (1.73, P = 0.01), ICA (2.37, P = 0.002), and ZnT8A (1.87, P = 0.03) independently predicted diabetes, whereas HLA type (high and moderate vs. low risk) and GAD65A did not (P = 0.81 and 0.86, respectively). CONCLUSIONS In relatives with one standard BAA, ZnT8A identified a subset at higher diabetes risk. ZnT8A predicted diabetes independently of ICA, the standard BAA, age, and HLA type. ZnT8A should be included in type 1 diabetes prediction and prevention studies.
Saline is a more appropriate solution for microvesicles for flow cytometric analyses

Microvesicles (MVs) are carriers of molecular and oncogenic signatures present in subsets of tumor cells and tumor-associated stroma, and a focus of cancer research. Although methods to detect MVs are mature, we were concerned that the buffer used could lead to false results when quantitating MVs by flow cytometry. In this work, we detected MVs by flow cytometry withthree different solutions: water, saline, and phosphate-buffered saline (PBS). The results demonstrated that PBS, when reacted with annexin V binding buffer, produced nano-sized vesicles even when there were no MVs in the sample. No similar events occurred in the saline and water groups (P < 0.01). Annexin V positive rate increased significantly when PBS was used as the buffer, compared to saline and water. These false negative results were also observed when we quantified some markers of MVs such as CD3 and CD19. A probable explanation for these findings is the production of insoluble Ca(H2PO4)2 or Ca3PO4 from calcium in the binding buffer and phosphate in PBS. Thus, considering the osmotic pressure of water, we suggest that saline is a more suitable buffer when counting MVs by flow cytometry.
Passive Sampling for Indoor and Outdoor Exposures to Chlorpyrifos, Azinphos-Methyl, and Oxygen Analogs in a Rural Agricultural Community

Background: Recent studies have highlighted the increased potency of oxygen analogs of organophosphorus pesticides. These pesticides and oxygen analogs have previously been identified in the atmosphere following spray applications in the states of California and Washington. Objectives: We used two passive sampling methods to measure levels of the ollowing organophosphorus pesticides: chlorpyrifos, azinphos-methyl, and their oxygen analogs at 14 farmworker and 9 non-farmworker households in an agricultural region of central Washington State in 2011. Methods: The passive methods included polyurethane foam passive air samplers deployed outdoors and indoors and polypropylene deposition plates deployed indoors. We collected cumulative monthly samples during the pesticide application seasons and during the winter season as a control. Results: Monthly outdoor air concentrations ranged from 9.2 to 199 ng/m3 for chlorpyrifos, 0.03 to 20 ng/m3 for chlorpyrifos-oxon, < LOD (limit of detection) to 7.3 ng/m3 for azinphos-methyl, and < LOD to 0.8 ng/m3 for azinphos-methyl-oxon. Samples from proximal households (≤ 250 m) had significantly higher outdoor air concentrations of chlorpyrifos, chlorpyrifos-oxon, and azinphos-methyl than did samples from nonproximal households (p ≤ 0.02). Overall, indoor air concentrations were lower than outdoors. For example, all outdoor air samples for chlorpyrifos and 97% of samples for azinphos-methyl were > LOD. Indoors, only 78% of air samples for chlorpyrifos and 35% of samples for azinphos-methyl were > LOD. Samples from farmworker households had higher indoor air concentrations of both pesticides than did samples from non-farmworker households. Mean indoor and outdoor air concentration ratios for chlorpyrifos and azinphos-methyl were 0.17 and 0.44, respectively. Conclusions: We identified higher levels in air and on surfaces at both proximal and farmworker households. Our findings further confirm the presence of pesticides and their oxygen analogs in air and highlight their potential for infiltration of indoor living environments. Citation: Gibbs JL, Yost MG, Negrete M, Fenske RA. 2017. Passive sampling for indoor and outdoor exposures to chlorpyrifos, azinphos-methyl, and oxygen analogs in a rural agricultural community. Environ Health Perspect 125:333–341; http://dx.doi. org/10.1289/EHP425
Anticardiolipin antibodies and 12-month graft function in kidney transplant recipients: a prognosis cohort survey

Background In kidney transplant recipients, anticardiolipin (ACL) antibodies without antiphospholipid syndrome (APS) are found in up to 38% of patients and could be associated with thrombotic events (TEs). However, the prognostic role of ACL regarding kidney transplant and patients outcomes have still not been well defined. Methods We conducted an observational, monocentric, retrospective cohort study including 446 kidney transplant recipients and standardized follow-up: 36-month allograft and patient survival, 12-month estimated glomerular filtration rate (eGFR) and 3- and 12-month screening biopsies. Results ACL tests were run on 247 patients, 101 were positive (ACL+ group, 41%) and 146 were negative (ACL- group, 59%). Allografts and patient survival within 36 months as TE were similar between both groups [hazard ratio (HR) = 1.18 and HR = 0.98, respectively]. The 12-month eGFR was significantly lower in the ACL+ group [median (95% confidence interval) 48.5 (35.1-60.3) versus 51.9 (39.1-65.0) mL/min/1.73 m2, P= 0.042]. ACL+ was independently associated with eGFR decrease (P = 0.04). In 12-month screening biopsies, tubular atrophy was significantly more severe in the ACL+ group compared with the ACL- group (P = 0.02). Conclusions ACL without APS before kidney transplantation is an independent risk factor of eGFR decline within the first year post-transplant without over-incidence of TEs. Specific immunosuppressive therapy including mammalian target of rapamycin inhibitors should be discussed in the future.
The cancer risk related to meat and meat products

Introduction Meat has been classified by International Agency for Research on Cancer (IARC) as carcinogenic to humans. The evidence and the implications for health are reviewed. Sources of data Evidence was obtained from published reports and systematic reviews published before and since the IARC decision. Areas of agreement Epidemiology indicates that processed meat products are associated with increased risk of colorectal cancer. Evidence for red meat and for other cancers remains tentative. Areas of controversy Several mechanisms for mutagenic effects of meat consumption have been identified but it is not clear which cause cancer in humans. The extent to which complete abstention from meat protects against cancer is also uncertain. Growing points Prospective studies on meat consumption in western populations will continue to illuminate the details of carcinogenesis, and effective strategies for reducing risk. Areas timely for developing research Further studies on the precise mechanisms of carcinogenesis in human populations would assist both food manufacturers and the general public to minimize risk.
HIV Infection, Immunosuppression, and Age at Diagnosis of Non-AIDS-Defining Cancers

Background It is unclear whether immunosuppression leads to younger ages at cancer diagnosis among people living with human immunodeficiency virus (PLWH). A previous study found that most cancers are not diagnosed at a younger age in people with AIDS, with the exception of anal and lung cancers. This study extends prior work to include all PLWH and examines associations between AIDS, CD4 count, and age at cancer diagnosis. Methods We compared the median age at cancer diagnosis between PLWH in the North American AIDS Cohort Collaboration on Research and Design and the general population using data from the Surveillance, Epidemiology and End Results Program. We used statistical weights to adjust for population differences. We also compared median age at cancer diagnosis by AIDS status and CD4 count. Results After adjusting for population differences, younger ages at diagnosis (P < .05) were observed for PLWH compared with the general population for lung (difference in medians = 4 years), anal (difference = 4), oral cavity/pharynx (difference = 2), and kidney cancers (difference = 2) and myeloma (difference = 4). Among PLWH, having an AIDS-defining event was associated with a younger age at myeloma diagnosis (difference = 4; P = .01), and CD4 count <200 cells/µL (vs ≥500) was associated with a younger age at lung cancer diagnosis (difference = 4; P = .006). Conclusions Among PLWH, most cancers are not diagnosed at younger ages. However, this study strengthens evidence that lung cancer, anal cancer, and myeloma are diagnosed at modestly younger ages, and also shows younger ages at diagnosis of oral cavity/pharynx and kidney cancers, possibly reflecting accelerated cancer progression, etiologic heterogeneity, or risk factor exposure in PLWH.