Transposase interaction with the β sliding clamp: Effects on insertion sequence proliferation and transposition rate

Insertion sequences (ISs) are ubiquitous and abundant mobile genetic elements in prokaryotic genomes. ISs often encode only one protein, the transposase, which catalyzes their transposition. Recent studies have shown that transposases of many different IS families interact with the β sliding clamp, a DNA replication factor of the host. However, it was unclear to what extent this interaction limits or favors the ability of ISs to colonize a chromosome from a phylogenetically-distant organism, or if the strength of this interaction affects the transposition rate. Here we describe the proliferation of a member of the IS1634 family in Acidiphilium over ~600 generations of cultured growth. We demonstrate that the purified transposase binds to the β sliding clamp of Acidiphilium, Leptospirillum and E. coli. Further, we also demonstrate that the Acidiphilium IS1634 transposase binds to the archaeal sliding clamp (PCNA) from Methanosarcina, and that the transposase encoded by Methanosarcina IS1634 binds to Acidiphilium β. Finally, we demonstrate that increasing the strength of the interaction between β and transposase results in a higher transposition rate in vivo. Our results suggest that the interaction could determine the potential of ISs to be mobilized in bacterial populations and also their ability to proliferate within chromosomesThis work was funded by the Subdirección General de Proyectos de Investigación of the Spanish Ministry for Economy and Competitiveness Grants No. CGL2010-17384 and AYA2011-24803, and by the European Research Council (ERC) Advanced Grant No. 250350 (IPBSL). HDM has a FPI fellowship from the Spanish Governmen

Respecting rights

This book takes as its starting point real life cases featuring ethical problems in the areas of: negotiating roles and boundaries, respecting rights, being fair, challenging and developing organisations and working with policy and politics. Each case opens with a brief introduction, is followed by two commentaries and ends with questions for reflection. The commentaries, written by authors from different countries, refer to relevant theories, concepts, practical matters, alternative courses of action and their implications. Chapter 3: Respecting rights. Introduction: Linda Briskman and María Jesús Úriz Pemán; Case 3.1: Issues of choice and coercion: working in a psychiatric hospital in the USA; Case 3.2: The reluctant vegan: the case of an older man in a Swedish care home; Case 3.3: Social work in Vietnam: a Dutch student’s perspective; Case 3.4: Ethical issues in international social work research: a case from India

Ethical practice under Covid-19

Questions of ethics lie at the heart of government responses to Covid-19, professional reactions and citizens’ behaviour. Such questions include: Do we value health or the economy? Who gets the protective equipment, ventilators or food vouchers? Is combatting loneliness worth the risk of spreading or contracting the virus? During May 2020, a group of academics in partnership with the International Federation of Social Workers (IFSW) launched a qualitative survey, asking for details of the ethical challenges faced by social workers during Covid-19. We identified six main themes: Creating and maintaining trusting, honest and empathic relationships via phone or internet with due regard to privacy and confidentiality, or in person with protective equipment. Prioritising service user needs and demands, which are greater and different due to the pandemic, when resources are stretched/unavailable and full assessments often impossible. Balancing service user rights, needs and risks against personal risk to social workers and others, in order to provide services as well as possible. Deciding whether to follow national and organisational policies, procedures or guidance (existing or new) or to use professional discretion in circumstances where the policies seem inappropriate, confused or lacking. Acknowledging and handling emotions, fatigue and the need for self-care, when working in unsafe and stressful circumstances. Using the lessons learned from working during the pandemic to rethink social work in the future

Practising ethically during Covid-19: social work challenges and responses

This article draws on findings of an international study of social workers’ ethical challenges during COVID-19, based on 607 responses to a qualitative survey. Ethical challenges included the following: maintaining trust, privacy, dignity and service user autonomy in remote relationships; allocating limited resources; balancing rights and needs of different parties; deciding whether to break or bend policies in the interests of service users; and handling emotions and ensuring care of self and colleagues. The article considers regional contrasts, the ‘ethical logistics’ of complex decision-making, the impact of societal inequities, and lessons for social workers and professional practice around the globe

Ethical Challenges for Social Workers during Covid-19: A Global Perspective

This report summarises the findings of an international study of the ethical challenges faced by social workers during the Covid-19 pandemic, undertaken during 6th-18th May 2020. 607 responses from 54 countries were received via an online survey, additional interviews and local surveys. Six key themes relating to social workers’ ethical challenges and responses were identified: 1. Creating and maintaining trusting, honest and empathic relationships via phone or internet with due regard to privacy and confidentiality, or in person with protective equipment. 2. Prioritising service user needs and demands, which are greater and different due to the pandemic, when resources are stretched or unavailable and full assessments often impossible. 3. Balancing service user rights, needs and risks against personal risk to social workers and others, in order to provide services as well as possible. 4. Deciding whether to follow national and organisational policies, procedures or guidance (existing or new) or to use professional discretion in circumstances where the policies seem inappropriate, confused or lacking. 5. Acknowledging and handling emotions, fatigue and the need for selfcare, when working in unsafe and stressful circumstances. 6. Using the lessons learned from working during the pandemic to rethink social work in the future

Ursodeoxycholic acid inhibits hepatic cystogenesis in experimental models of polycystic liver disease

Background & Aims: Polycystic liver diseases (PLDs) are genetic disorders characterized by progressive biliary cystogenesis. Current therapies show short-term and/or modest beneficial effects. Cystic cholangiocytes hyperproliferate as a consequence of diminished intracellular calcium levels ([Ca2+](i)). Here, the therapeutic value of ursodeoxycholic acid (UDCA) was investigated. Methods: Effect of UDCA was examined in vitro and in polycystic (PCK) rats. Hepatic cystogenesis and fibrosis, and the bile acid (BA) content were evaluated from the liver, bile, serum, and kidneys by HPLC-MS/MS. Results: Chronic treatment of PCK rats with UDCA inhibits hepatic cystogenesis and fibrosis, and improves their motor behaviour. As compared to wild-type animals, PCK rats show increased BA concentration ([BA]) in liver, similar hepatic Cyp7a1 mRNA levels, and diminished [BA] in bile. Likewise, [BA] is increased in cystic fluid of PLD patients compared to their matched serum levels. In PCK rats, UDCA decreases the intrahepatic accumulation of cytotoxic BA, normalizes their diminished [BA] in bile, increases the BA secretion in bile and diminishes the increased [BA] in kidneys. In vitro, UDCA inhibits the hyperproliferation of polycystic human cholangiocytes via a PI3K/AKT/MEK/ERK1/2-dependent mechanism without affecting apoptosis. Finally, the presence of glycodeoxycholic acid promotes the proliferation of polycystic human cholangiocytes, which is inhibited by both UDCA and tauro-UDCA. Conclusions: UDCA was able to halt the liver disease of a rat model of PLD through inhibiting cystic cholangiocyte hyperproliferation and decreasing the levels of cytotoxic BA species in the liver, which suggests the use of UDCA as a potential therapeutic tool for PLD patients. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserve