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Protein arginine methylation is involved in many biological processes and can be enhanced in cancer. In mammals, these reactions are catalyzed on multiple substrates by a family of nine protein arginine methyltransferases (PRMTs). However, conditions that may regulate the activity of each enzyme and that may help us understand the physiological role of PRMTs have not been fully established. Previous studies had suggested unexpected effects of temperature and ionic strength on PRMT7 activity. Here we examine in detail the effects of temperature, pH, and ionic strength on recombinant human PRMT1, PRMT5, and PRMT7. We confirmed the unusual temperature dependence of PRMT7, where optimal activity was observed at 15 °C. On the other hand, we found that PRMT1 and PRMT5 are most active near physiological temperatures of 37 °C. However, we showed all three enzymes still have significant activity at 0 °C. Furthermore, we determined that PRMT1 is most active at a pH of about 7.7, while PRMT5 activity is not dependent on pH in the range of 6.5 to 8.5. Significantly, PRMT7 is most active at an alkaline pH of 8.5 but shows little activity at the physiological intracellular pH of about 7.2. We also detected decreased activity at physiological salt conditions for PRMT1, PRMT5, and PRMT7. We demonstrate that the loss of activity is due to the increasing ionic strength. Taken together, these results open the possibility that PRMTs respond in cells undergoing temperature, salt, or pH stress and demonstrate the potential for invivo regulation of protein arginine methylation.

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Lead (Pb

Care home residents with stroke have higher levels of disability and poorer access to health services than those living in their own homes. We undertook observations and semi-structured interviews (n = 28 participants) with managers, staff, residents who had experienced a stroke and their relatives in four homes in London, England, in 2018/2019. Thematic analysis revealed that residents' needs regarding valued activity and stroke-specific care and rehabilitation were not always being met. This resulted from an interplay of factors: staff's lack of recognition of stroke and its effects; gaps in skills; time pressures; and the prioritisation of residents' safety. To improve residential care provision and residents' quality of life, care commissioners, regulators and providers may need to re-examine how care homes balance safety and limits on staff time against residents' valued activity, alongside improving access to specialist healthcare treatment and support.

Women experiencing incarceration (WEI) in the United States are disproportionately impacted by HIV, yet HIV pre-exposure prophylaxis (PrEP) is underutilized by women in the United States. In order to inform an intervention to promote PrEP initiation during incarceration and facilitate linkage to PrEP care following release from incarceration, we conducted individual, semistructured qualitative interviews with WEI (N = 21) and key stakeholders (N = 14). While WEI had little or no previous knowledge about PrEP, they viewed it as something that would benefit women involved in the criminal justice system. Participants stated that HIV-related stigma and underestimation of HIV risk might serve as barriers to PrEP initiation during incarceration. Participants reported that competing priorities, difficulty scheduling an appointment, and lack of motivation could interfere with linkage to PrEP care in the community. Further, cost, substance use, and difficulty remembering to take the medication were cited most commonly as likely barriers to adherence.

Background Fentanyl and related compounds have recently saturated the illicit drug supply in the United States, leading to unprecedented rates of fatal overdose. Individuals who are incarcerated are particularly vulnerable, as the burden of opioid use disorder is disproportionately higher in this population, and tolerance generally decreases during incarceration. Methods We conduct a systematic search for publications about fentanyl overdoses during incarceration in PubMed and PsycINFO, as well as lay press articles in Google, from January 1, 2013 through March 30th, 2021. Results Not a single fentanyl overdose was identified in the medical literature, but 90 overdose events, comprising of 76 fatal and 103 nonfatal fentanyl overdoses, were identified in the lay press. Among the 179 overdoses, 138 occurred in jails and 41 occurred in prisons, across the country. Conclusions Fentanyl-related overdoses are occurring in correctional facilities with unknown but likely increasing frequency. In addition to the need for improved detection and reporting, immediate efforts to 1) increase understanding of the risks of fentanyl and how to prevent and treat overdose among correctional staff and residents, 2) ensure widespread prompt availability of naloxone and 3) expand the availability of medications to treat opioid use disorder for people who are incarcerated will save lives.

This study investigates the overall volumetric oxygen transfer coefficient (KLa) in multiphase hydrocarbon-based bioprocess under a range of hydrocarbon concentrations (HC), solid loadings (deactivated yeast) (SL) and superficial gas velocities (UG) in a bubble column reactor (BCR). KLa increased with increasing UG in the air-water system; due to an increase in the number of small bubbles which enhanced gas holdup. In air-water-yeast systems, the initial addition of yeast increased KLa significantly. Further increases in SL reduced KLa, due to increases in the bubble size with increasing SL. KLa decreased when HC was added in air-water-hydrocarbon systems. However, UG, SL and HC affected KLa differently in air-water-yeast-hydrocarbon systems: an indication of the complex interactions between the yeast and hydrocarbon phases which changed the system's hydrodynamics and therefore affected KL. This work illustrates the effect of the operating conditions (SL, HC and UG) on oxygen transfer behaviour in multiphase systems.

I write into the haecceity of recent events in and around my teaching in environmental education to explore the concept of thisness as pedagogy.

Background Congenital diaphragmatic hernia (CDH) is a severe birth defect associated with high perinatal mortality and long-term morbidity. The etiology of CDH is poorly understood although abnormal retinoid signaling has been proposed to contribute to abnormal diaphragm development. Existing epidemiological data suggest that inadequate dietary vitamin A intake is a risk factor for developing CDH. Methods Using a mouse model of teratogen-induced CDH, the objective of this study was to test the hypothesis that low maternal vitamin A intake contributes to abnormal diaphragm development. To test this hypothesis, we optimized a model of altered maternal dietary vitamin A intake and a teratogenic model of CDH in mice that recapitulates the hallmark features of posterolateral diaphragmatic hernia in humans. Results Our data uniquely show that low maternal dietary vitamin A intake and marginal vitamin A status increases the incidence of teratogen-induced CDH in mice. Conclusion Low dietary vitamin A intake and marginal vitamin A status lead to an increased incidence of teratogen-induced CDH in mice, highlighting the importance of adequate dietary vitamin A intake and CDH risk. Impact This study describes and validates a mouse model of altered maternal and fetal vitamin A status. This study links existing epidemiological data with a mouse model of teratogen-induced congenital diaphragmatic hernia, highlighting the importance of low maternal vitamin A intake as a risk factor for the development of congenital diaphragmatic hernia. This study supports the Retinoid Hypothesis, which posits that the etiology of congenital diaphragmatic hernia is linked to abnormal retinoid signaling in the developing diaphragm.

Correctional facilities provide health care to large numbers of medically underserved people. As such, preventive health in correctional settings is an important yet underused investment in public health. Because they often have histories of poor access to health care, the justice-involved population is more likely than the general population to be diagnosed with advanced-stage cancers. We report on the first 2 years of an ongoing collaboration between a state correctional system and state health department to implement annual colorectal cancer screening for sentenced people using fecal immunochemical testing (FIT). Preparation for the annual iterations begins in January, and patient engagement begins in March. In the first year of implementation (2018), 1396 of 1856 (75.2%) sentenced people completed an eligibility screen, and 254 of 321 (79.1%) eligible patients completed a FIT (eligible patients were aged ≥50 [≥45 if Black] in year 1 [lowered to ≥45 in year 2] and reported no previous relevant medical or family history of colorectal cancer); 54 (21.3%) completed FITs were positive. Of the 54 patients with positive FITS, 33 (61.1%) completed follow-up colonoscopies resulting in the identification of polyps in 26 (48.1%) patients with a positive FIT. We found invasive adenocarcinoma for 2 (3.7%) of the positive FITs (6.1% of colonoscopies performed). In the second year (2019), after a conversion from paper to tablet-based eligibility screening, 1707 of 2059 (82.9%) sentenced people completed an eligibility screen, and 200 of 285 (70.2%) eligible patients completed a FIT, 27 (13.5%) of whom had a positive result. We share lessons learned about implementing mass screening to encourage further communication among departments of health and corrections to advance preventive health.

Purpose The purpose of this paper is to describe the course, “Designing Education for Better Prisoner and Community Health,” which provided students with the knowledge, skills and resources needed to build real-world health education materials for persons who are criminal justice involved. Design/methodology/approach A multiphase engaged scholarship course was designed and implemented through the Brown University School of Public Health in Rhode Island, USA. Findings Students collaborated closely with instructors, subject matter experts and affected community members to develop highly tailored health education projects across six topic areas. The structure and outcomes of the paper are described with the hope that other instructors and institutions might replicate components of the model. Originality/value Engaged scholarship in public health can provide students with rich, collaborative learning experiences, and when executed effectively, these endeavors can provide underserved communities with robust and informed health education interventions and programs.

Synthetically straightforward pi-extension of helically chiral N,N,O,O-boron chelated borondipyrromethenes (BODIPYs) has been achieved by incorporation of naphthyl rings into the BODIPY 3- and 5-positions. The effect of this extension on the photophysical and chiroptical properties is strongly dependent on the regiochemistry of the naphthyl substituents (4 exo, 4 lin, 4 endo). The most helicene-like regioisomer 4 endo is a near infra-red (NIR) emitter (lambda(em)(max)=751 nm) with an emission band between 675-875 nm, displaying circularly polarised luminescence (CPL) with a luminescence dissymmetry factor, vertical bar g(lum)vertical bar=5.7x10(-3) and CPL brightness, B-CPL=27, rivalling the best NIR CPL-emitting small organic molecules reported to date.

Inflammation and oxidative stress in pancreatic islets amplify the appearance of various post-translational modifications (PTMs) to self-proteins. Herein, we identified a select group of carbonylated islet proteins arising before the onset of hyperglycemia in non-obese diabetic mice. Of interest, we identified carbonyl modification of the prolyl-4-hydroxylase beta subunit (P4Hb) that is responsible for proinsulin folding and trafficking as an autoantigen in both human and murine type 1 diabetes. We found the carbonylated P4Hb is amplified in stressed islets coincident with decreased glucose-stimulated insulin secretion and altered proinsulin to insulin ratios. Autoantibodies against P4Hb were detected in prediabetic NOD mice and in early human type 1 diabetes prior to the onset of anti-insulin autoimmunity. Moreover, we identify autoreactive CD4+ T cell responses toward carbonyl-P4Hb epitopes in the circulation of patients with type 1 diabetes. Our studies provide mechanistic insight into the pathways of proinsulin metabolism and in creating autoantigenic forms of insulin in type 1 diabetes.

For over a decade RNA interference (RNAi) has been an important molecular tool for functional genomics studies in parasitic flatworms. Despite this, our understanding of RNAi dynamics in many flatworm parasites, such as the temperate liver fluke (Fasciola hepatica), remains rudimentary. The ability to maintain developing juvenile fluke in vitro provides the opportunity to perform functional studies during development of the key pathogenic life stage. Here, we investigate the RNAi competence of developing juvenile liver fluke. Firstly, all life stages examined possess, and express, core candidate RNAi effectors encouraging the hypothesis that all life stages of F. hepatica are RNAi competent. RNAi effector analyses supported growing evidence that parasitic flatworms have evolved a separate clade of RNAi effectors with unknown function. Secondly, we assessed the impact of growth/development during in vitro culture on RNAi in F. hepatica juveniles and found that during the first week post-excystment liver fluke juveniles exhibit quantitatively lower RNAi mediated transcript knockdown when maintained in growth inducing media. This did not appear to occur in older in vitro juveniles, suggesting that rapidly shifting transcript dynamics over the first week following excystment alters RNAi efficacy after a single 24 h exposure to double stranded (ds)RNA. Finally, RNAi efficiency was found to be improved through use of a repeated dsRNA exposure methodology that has facilitated silencing of genes in a range of tissues, thereby increasing the utility of RNAi as a functional genomics tool in F. hepatica., Graphical abstract Image 1, Highlights • All F. hepatica life stages express the RNAi machinery for a functional pathway. • RNAi-mediated knockdown in juvenile F. hepatica is affected by in vitro growth. • Repeated dsRNA exposures ensure longevity of transcript and protein knockdown. • This provides a basis for a robust RNAi platform in F. hepatica juveniles.

It is important to understand how incarcerated men conceptualize fatherhood for reentry. Sixteen interviews explored attitudes and feelings about parenthood, family planning, and challenges and strengths regarding fatherhood. Transcriptions were analyzed for themes using open coding. Parenting themes: being active in children's lives, financial stability, and giving children better lives. Family planning themes: preventing sexually transmitted infection, creating stable families, importance of family planning, and birth control methods. Men were motivated to be stable fathers and utilize family planning to create stability; men expressed need for better partner communication. Fathers struggled to provide support/stability for children but expressed openness to learning parenting skills and family planning methods. Reentry strategies may address these themes to rehabilitate men and enhance family planning.

Managing the intertemporal risk of optimally constructed multifactor portfolios adds to performance. The increases in Sharpe ratios are in addition to the utility that investors gain from controlli...

Objectives Rates of unintended pregnancies in women with a history of incarceration are high and access to contraception before and after arrest can be limited. Individualized counseling can better prepare women for healthy pregnancy or provide an opportunity for contraceptive education and access within correctional facilities. In this study, we assessed the efficacy of motivational interviewing as an individualized intervention to increase the initiation of contraceptive methods while incarcerated and continuation after release in female inmates who wanted to avoid pregnancy for at least one year after release. Study design We performed an RCT in a population of incarcerated women who wanted to avoid pregnancy. Women were randomized to either a computer-assisted motivational interviewing intervention group (n = 119) or an educational video with counseling control group. (n = 113). The primary outcome was initiation of a method of birth control prior to release from the correctional facility. Results Initiation of contraception was higher in the intervention group (56% vs. 42%, p = 0.03), but this difference was not significant after controlling for number of male partners within the year prior to incarceration. There was no difference between the groups in the rates of pregnancies or STIs or continuation of contraception after release, which was generally low (21%). Conclusion Computer-assisted motivational interviewing did not improve uptake or continuation of contraception in this study. Implications Periods of incarceration provide an opportunity to offer contraceptive services to women who want to avoid a pregnancy. Motivational interviewing may not be an effective method to affect contraceptive behaviors in this population. Future research should explore the family planning values and preferences of women who become involved with the correctional system.

Pre-exposure prophylaxis (PrEP) may be an effective approach to prevent HIV among people who are currently incarcerated or who have been recently released from incarceration. However, awareness and interest in PrEP are largely unknown in this population. This study assessed 417 incarcerated men's lifetime HIV risk engagement and gauged their interest and willingness to take PrEP. Twenty percent reported ever injecting drugs and 4% ever having sex with a man without a condom; 88% had never heard of PrEP. More White men had heard of PrEP, but higher percentages of men of color were interested in learning more about PrEP and willing to take PrEP to prevent HIV. Future interventions should focus on PrEP education and uptake among individuals who are incarcerated.

As overdoses due to opioids rise, medications for opioid use disorder (MOUD) continue to be underemployed, resulting in limited access to potentially life-saving treatment. Substance use disorders are prevalent in individuals who are incarcerated, and these individuals are at increased risk for death postrelease due to overdose. Few jails and prisons offer MOUD and most limit access. Extended-release buprenorphine (XR-BUP), a novel monthly injectable MOUD formulation, could be uniquely poised to address treatment access in correctional settings.This study linked a retrospective cohort design of statewide datasets to evaluate the real-world use of XR-BUP. The study included individuals (N = 54) who received XR-BUP while incarcerated from January 2019 through February 2022. The study was conducted at the Rhode Island Department of Corrections, with the nation's first comprehensive statewide correctional MOUD program.Fifty-four individuals received a combined total of 162 injections during the study period. The study found no evidence of tampering with the injection site, indicating no attempts by participants to remove, hoard, or divert the medication. Sixty-one percent reported at least one adverse effect after injections were received, with an average of 2.8 side effects. Sixty-one percent of those released on XR-BUP engaged in MOUD after release, 30 % continued with XR-BUP.XR-BUP is feasible and acceptable in correctional settings. XR-BUP addresses administrative concerns of diversion that obstruct lifesaving MOUD and offers another safe and effective treatment option. Further studies and trials should continue to assess this novel medication's ability to treat opioid addiction in the correctional setting and upon release to the community.

Net photoreduction of divalent mercury (Hg(II)) and volatilization of photoreduction products (i.e., elemental mercury (Hg(0))/dissolved gaseous mercury (DGM)) is a mechanism by which mercury burdens in ecosystems are lessened. The effects of salinity on mercury photoreactions were investigated while controlling the concentration of DOM (1 kDa) using natural surface water from the tidal Jijuktu'kwejk (Cornwallis River) and processed with a tangential ultrafiltration-dilution technique. Pseudo first-order rate constants in estuarine water salinity dilutions ranged between 0.22 h

Methionine addiction, found in all types of cancer investigated, is because of the overuse of methionine by cancer cells for excess transmethylation reactions. In the present study, we compared the histone H3 lysine-methylation status and degree of malignancy between methionine-addicted cancer cells and their isogenic methionine-independent revertants, selected by their growth in low concentration of methionine. The methionine-independent revertans can grow on low levels of methionine or independently of exogenous methionine using methionine precursors, as do normal cells. In the methionine-independent revertants, the excess levels of trimethylated histone H3 lysine marks found in the methionine-addicted parental cancer cells were reduced or lost, and their tumorigenicity and experimental metastatic potential in nude mice were also highly reduced. Methionine addiction of cancer is linked with malignancy and hypermethylation of histone H3 lysines. The results of the present study thus provide a unique framework to further understand a fundamental basis of malignancy.

Incarcerated men are at high risk for sexually transmitted infections (STIs) and unintended partner pregnancy postrelease. Limited research has been invested in developing and testing treatments targeting risky sexual behavior and unwanted pregnancy for this at-risk population. Motivational interviewing (MI) is a promising behavioral intervention for decreasing risky sexual behaviors. This study assessed the feasibility and acceptability of MI for family planning and risky sexual behaviors with incarcerated men nearing release. Preliminary efficacy of the MI intervention was also compared to an educational control group. Thirty-two men were assessed at baseline and randomized to one 90-min session. Assessment occurred 2 months after release. MI was feasibly administered, and participants were highly satisfied with both treatments. In addition, those who received MI reported higher rates of condom use with casual partners, higher rates of partner use of hormonal contraceptives, and slightly higher rates of sex that was protected against pregnancy. Increases are readiness to discuss family planning with sexual partners, as well as reported frequency of these discussions, and increases in family planning knowledge were also found in those randomized to MI. The findings from this study indicate the need to further assess MI with this population with a full-scale clinical trial. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Ovarian cancer patients frequently develop chemotherapy resistance, limiting treatment options. We have previously shown that individuality in fibroblast growth factor 1 (FGF1) expression influences survival and chemotherapy response.We used MTT assays to assess chemosensitivity to cisplatin and carboplatin following shRNA-mediated knockdown or heterologous over-expression of FGF1 (quantified by qRT-PCR and immunoblot analysis), and in combination with the FGFR inhibitors AZD4547 and SU5402, the ATM inhibitor KU55933 and DNA-PK inhibitor NU7026. Immunofluorescence microscopy was used to quantify the FGF1-dependent timecourse of replication protein A (RPA) and γH2AX foci formation.Pharmacological inhibition of FGF signalling reversed drug resistance in immortalised cell lines and in primary cell lines from drug-resistant ovarian cancer patients, while FGF1 over-expression induced resistance. Ataxia telangiectasia mutated (ATM) phosphorylation, but not DNA adduct formation was FGF1 dependent, following cisplatin or carboplatin challenge. Combining platinum drugs with the ATM inhibitor KU55933, but not with the DNA-PK inhibitor NU7026 re-sensitised resistant cells. FGF1 expression influenced the timecourse of damage-induced RPA and γH2AX nuclear foci formation.Drug resistance arises from FGF1-mediated differential activation of high-fidelity homologous recombination DNA damage repair. FGFR and ATM inhibitors reverse platinum drug resistance, highlighting novel combination chemotherapy approaches for future clinical trial evaluation.

Background/Aim: Methionine addiction is a fundamental and general hallmark of cancer, termed the Hoffman effect. Methionine addiction is due to excessive use of and dependence on methionine by cancer cells. In the present report, we correlated the extent of methionine addiction and degree of malignancy with the amount and stability of methylated histone H3 lysine marks. Materials and Methods: We established low- and high-malignancy variants from a parental human pancreatic-cancer cell line and compared their sensitivity to methionine restriction and histone H3 lysine methylation status. Results: A low-malignancy, low-methionine-addiction revertant of the parental pancreatic-cancer cell line had less methylated H3K9me3 and was less sensitive to methionine restriction effected by recombinant methioninase (rMETase) than the parental cell line. A high-malignancy variant of the pancreatic cancer cell line had increased methylated H3K9me3 and was more sensitive to methionine restriction by rMETase with regard to inhibition of proliferation and to instability of histone H3 lysine methylation than the parental cell line. Orthotopic malignancy in nude mice was reduced in the low-methionine-addiction revertant and greater in the high-malignancy variant than in the parental cell line. Conclusion: The present study indicates that the degree of malignancy is linked to the extent of methionine addiction and the level and instability of trimethylation of histone H3, suggesting these phenomena are linked as a fundamental basis of oncogenic transformation.

If current trends continue, non-Hispanic whites will no longer be a majority in the United States (US) by 2050.1 1 Frey classifies groups differently than the federal government. Most notably, he t...