Vertebrate DNA damage tolerance requires the C-terminus but not BRCT or transferase domains of REV1

REV1 is central to the DNA damage response of eukaryotes through an as yet poorly understood role in translesion synthesis. REV1 is a member of the Y-type DNA polymerase family and is capable of in vitro deoxycytidyl transferase activity opposite a range of damaged bases. However, non-catalytic roles for REV1 have been suggested by the Saccharomyces cerevisiae rev1-1 mutant, which carries a point mutation in the N-terminal BRCT domain, and the recently demonstrated ability of the mammalian protein to interact with each of the other translesion polymerases via its extreme C-terminus. Here, we show that a region adjacent to this polymerase interacting domain mediates an interaction with PCNA. These C-terminal domains of REV1 are necessary, although not sufficient, for effective tolerance of DNA damage in the avian cell line DT40, while the BRCT domain and transferase activity are not directly required. Together these data provide strong support for REV1 playing an important non-catalytic role in coordinating translesion synthesis. Further, unlike in budding yeast, rad18 is not epistatic to rev1 for DNA damage tolerance suggesting that REV1 and RAD18 play largely independent roles in the control of vertebrate translesion synthesis

Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells

<p>Abstract</p> <p>Background</p> <p>The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route.</p> <p>Results</p> <p>Here we analysed viral entry in wild type BeWo (CCR5⁺, CXCR4⁺) and BeWo-CD4⁺(CD4⁺, CCR5⁺, CXCR4⁺) cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted.</p> <p>Conclusion</p> <p>Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.</p

Converging roads: the latest science from the 2017 IAS HIV Cure and Cancer Forum

Conference presented in the 2017 IAS HIV Cure and Cancer Forum took place in Paris on 22–23 July.S

Surveillance practices, risks and responses in the post pandemic university

This paper describes and critiques how surveillance is situated and evolving in higher education settings, with a focus on the surveillance of teaching and learning. It argues that intensifying practices of datafication and monitoring in universities echo those in broader society, and that the Covid-19 global pandemic has both exacerbated these practices and made them more visible. Surveillance brings risks to learning relationships and academic and work practices, as well as reinforcing economic models of extraction and inequalities in education and society. Responses to surveillance practices include resistance, advocacy, education, regulation and investment, and a number of these responses are examined here. Drawing on scholarship and practice, the paper provides an in-depth overview of this topic for people in university settings including those in leadership positions, learning technology roles, educators and students. The authors are part of an international network of researchers, educators and university leaders who are working together to develop new approaches to surveillance futures for higher education. Authors are based in Canada, South Africa, the United Kingdom and the United States, and this paper reflects those specific contexts

Passive Coping Strategies During Repeated Social Defeat Are Associated With Long-Lasting Changes in Sleep in Rats

Exposure to severe stress has immediate and prolonged neuropsychiatric consequences and increases the risk of developing Posttraumatic Stress Disorder (PTSD). Importantly, PTSD develops in only a subset of individuals after exposure to a traumatic event, with the understanding of this selective vulnerability being very limited. Individuals who go on to develop PTSD after a traumatic experience typically demonstrate sleep disturbances including persistent insomnia and recurrent trauma-related nightmares. We previously established a repeated social defeat paradigm in which rats segregate into either passively or actively coping subpopulations, and we found that this distinction correlates with measures of vulnerability or resilience to stress. In this study, we examined differences between these two behavioral phenotypes in sleep changes resulting from repeated social defeat stress. Our data indicate that, compared to control and actively coping rats, passively coping rats have less slow-wave sleep (SWS) for at least 2 weeks after the end of a series of exposures to social defeat. Furthermore, resilient rats show less exaggerated motor activation at awakenings from rapid eye movement (REM) sleep and less fragmentation of REM sleep compared to control and passively coping rats. Together, these data associate a passive coping strategy in response to repeated social defeat stress with persisting sleep disturbances. Conversely, an active coping strategy may be associated with resilience to sleep disturbances. These findings may have both prognostic and therapeutic applications to stress-associated neuropsychiatric disorders, including PTSD

Towards Multidisciplinary HIV-Cure Research: Integrating Social Science with Biomedical Research

The quest for a cure for HIV remains a timely and key challenge for the HIV research community. Despite significant scientific advances, current HIV therapy regimens do not completely eliminate the negative impact of HIV on the immune system; and the economic impact of treating all people infected with HIV globally, for the duration of their lifetimes, presents significant challenges. This article discusses, from a multi-disciplinary approach, critical social, behavioral, ethical, and economic issues permeating the HIV cure research agenda. As part of a search for an HIV cure, both the perspective of patients/participants and clinical researchers should be taken into account. In addition, continued efforts should be made to involve and educate the broader community

Surveillance practices, risks and responses in the post pandemic university

This paper describes and critiques how surveillance is situated and evolving in higher education settings, with a focus on the surveillance of teaching and learning. It argues that intensifying practices of datafication and monitoring in universities echo those in broader society, and that the Covid-19 global pandemic has both exacerbated these practices and made them more visible. Surveillance brings risks to learning relationships and academic and work practices, as well as reinforcing economic models of extraction and inequalities in education and society. Responses to surveillance practices include resistance, advocacy, education, regulation and investment, and a number of these responses are examined here. Drawing on scholarship and practice, the paper provides an in-depth overview of this topic for people in university settings including those in leadership positions, learning technology roles, educators and students. The authors are part of an international network of researchers, educators and university leaders who are working together to develop new approaches to surveillance futures for higher education. Authors are based in Canada, South Africa, the United Kingdom and the United States, and this paper reflects those specific contexts

Knowledge gaps in economic costs of invasive alien fish worldwide

Peer reviewe

Surveillance practices, risks and responses in the post pandemic university

This paper describes and critiques how surveillance is situated and evolving in higher education settings, with a focus on the surveillance of teaching and learning. It argues that intensifying practices of datafication and monitoring in universities echo those in broader society, and that the Covid-19 global pandemic has both exacerbated these practices and made them more visible. Surveillance brings risks to learning relationships, academic and work practices, as well as reinforcing economic models of extraction and inequalities in education and society. Responses to surveillance practices include resistance, advocacy, education, regulation and investment, and a number of these responses are examined here. Drawing on scholarship and practice, the paper provides an in-depth overview of this topic for people in university settings including those in leadership positions, learning technology roles, educators and students. The authors are part of an international network of researchers, educators and university leaders who are working together to develop new approaches to surveillance futures for higher education: https://aftersurveillance.net/. Authors are based in Canada, South Africa, the United Kingdom and the United States, and this paper reflects those specific contexts

Surveillance practices, risks and responses in the post pandemic university

This paper describes and critiques how surveillance is situated and evolving in higher education settings, with a focus on the surveillance of teaching and learning. It argues that intensifying practices of datafication and monitoring in universities echo those in broader society, and that the Covid-19 global pandemic has both exacerbated these practices and made them more visible. Surveillance brings risks to learning relationships and academic and work practices, as well as reinforcing economic models of extraction and inequalities in education and society. Responses to surveillance practices include resistance, advocacy, education, regulation and investment, and a number of these responses are examined here. Drawing on scholarship and practice, the paper provides an in-depth overview of this topic for people in university settings including those in leadership positions, learning technology roles, educators and students. The authors are part of an international network of researchers, educators and university leaders who are working together to develop new approaches to surveillance futures for higher education. Authors are based in Canada, South Africa, the United Kingdom and the United States, and this paper reflects those specific contexts