Nicolas Levrat, Yuliya Kaspiarovich, Christine Kaddous, and Ramses A Wessel (eds), The EU and its Member States’ joint participation in international agreements (Hart 2022)

To be Published in EJLS Issue 14(2) in January 2023The EU and its Member States are subject to both EU and international law when participating in international agreements. Indeed, EU external relations law finds itself at the intersection of these two fields of law which results in complex legal constellations. These complexities are exactly the topic of the volume on ‘The EU and its Member States’ Joint Participation in International Agreements’ edited by Nicolas Levrat, Yuliya Kaspiarovich, Christine Kaddous, and Ramses A Wessel. The volume collects the output of an online conference organised in November 2020 at the Global Studies Institute of the University of Geneva. In the spirit of ‘joint participation’, almost all chapters of the volume have been written by a team made up of a senior and a more junior scholar’, a set-up that this reviewer is appreciative of

The HIV-2 OGH double reporter virus shows that HIV-2 is less cytotoxic and less sensitive to reactivation from latency than HIV-1 in cell culture

A better understanding of HIV-1 latency is a research priority in HIV cure research. Conversely, little is known about the latency characteristics of HIV-2, the closely related human lentivirus. Though both viruses cause AIDS, HIV-2 infection progresses more slowly with significantly lower viral loads, even when corrected for CD4+ T cell counts. Hence a direct comparison of latency characteristics between HIV-1 and HIV-2 could provide important clues towards a functional cure.Transduction of SupT1 cells with single-round HIV-1 and HIV-2 viruses with an enhanced green fluorescent protein (eGFP) reporter showed higher levels of eGFP expression for HIV-2 than HIV-1, while HIV-1 expression appeared more cytotoxic. To compare HIV-1 and HIV-2 gene expression, latency and reactivation in more detail, we have generated HIV-2 OGH, a replication deficient, near full- length, double reporter virus that discriminates latently and productively infected cells in cell culture. This construct is based on HIV-1 OGH, and to our knowledge, first of its kind for HIV-2. Using this construct we have observed a higher eGFP expression for HIV-2, but higher losses of HIV-1 transduced cells in SupT1 and Jurkat cells and a reduced sensitivity of HIV-2 for reactivation with TNF-α. In addition, we have analysed HIV-2 integration sites and their epigenetic environment. HIV-1 and HIV-2 share a preference for actively transcribed genes in gene-dense regions and favor active chromatin marks while disfavoring methylation markers associated with heterochromatin. In conclusion the HIV-2 OGH construct provides an interesting tool for studying HIV-2 expression, latency and reactivation. As simian immunodeficiency virus (SIV) and HIV-2 have been proposed to model a functional HIV cure, a better understanding of the mechanisms governing HIV-2 and SIV latency will be important to move forward. Further research is needed to investigate if HIV-2 uses similar mechanisms as HIV-1 to achieve its integration site selectivity

The European Court of Justice and the two lighthouse functions of social law in the European legal space

Published online: 31 July 2023The article explores how social law operates as a “lighthouse” in the case-law of the European Court of Justice. It is argued that social law has had such guiding functions at two different levels, closely connected to the evolution of the Union’s competences. Firstly, the economic integration envisioned by the drafters of the Rome Treaty coincided with the unprecedented development of social security law and labour law in the founding Member States following World War II. Although the EEC had initially limited competences on social security and labour matters, the Court could not simply ignore that development when it applied and interpreted Community—and later on EU—rules of an essentially economic nature. The first lighthouse function of social law and social rights in Community law thus came from Member States’ arguments based on the need to preserve their social policies in the broad sense, which prompted the Court to accept nuances to the effect of EU free movement and competition rules. Secondly, the EU itself has gained increasing competences over time in matters connected to social law. The development of a vast body of EU social law, as interpreted by the Court, has thus increasingly served as a lighthouse for the Member States, supplemented by the fundamental rights connected to “solidarity” contained in the Charter of fundamental rights of the EU. The article concludes that today’s Social Europe would not be what it is without the Court’s contribution. Its case-law upholds concrete protection afforded by EU law to migrant and non-migrant citizens and guarantees the principles of equal treatment and non-discrimination in employment and occupation without losing sight of national diversity where EU law does not command uniform solutions. It acknowledges the fact that Member States’ social policies may have an impact on the scope of EU rules governing the establishment of the internal market and competition. The Court thus plays a central role in keeping both lighthouse functions of social law illuminating the European legal space

Analysis of ex vivo HIV-1 infection in a controller-discordant couple

Objectives: Elite controllers (EC) are a rare group of individuals living with HIV-1 who naturally control HIV-1 replication to levels below the limit of detection without antiretroviral therapy (ART) and rarely progress to AIDS. The mechanisms contributing to this control remain incompletely elucidated. In the present study, we have assessed whether cellular host factors could modulate HIV-1 replication post-entry in a controller-discordant couple living with HIV-1. Methods: CD4 T cells from a controller-discordant couple, one partner being an EC and the other an HIV-1 progressor (PR), and healthy controls (HC) were isolated, activated and infected with VSV-G pseudotyped yellow fluorescent protein-encoding single-round HIV-1 virus (HIV-YFP). Viral reverse transcripts, 2-LTR circles and integrated proviral HIV-1 DNA were monitored by quantitative PCR (qPCR) and integration sites were analysed. We further measured LEDGF/p75 and p21 mRNA expression levels by qPCR. Results: Infection of activated CD4 T cells with HIV-YFP was reduced in EC compared with the PR partner, and HC. Evaluation of viral DNA forms suggested a block after entry and during the early steps of HIV-1 reverse transcription in EC. The integration site distribution pattern in EC, PR and HC was similar. The p21 expression in CD4 T cells of EC was elevated compared with the PR or HC, in line with previous work. Conclusions: Our study suggests a reduced permissiveness to HIV-1 infection of CD4 T cells from EC due to a block of HIV-1 replication after entry and before integration that might contribute to the EC phenotype in our patient.status: publishe

The Influence of Everyday Acoustic Environments on the Challenging Behavior in Dementia: A Participatory Observation Study in Nursing Homes

Challenging behavior (CB) is a group of behaviors, reactions and symptoms due to dementia, which can be challenging for the caregivers. The study aims to research the influence of acoustics on CB in people with dementia (PwD). An ethnographic method was used to study the daily life of PwD in their nursing homes with a specific focus on how people react to everyday environmental sounds. Thirty-five residents were included in the sample based on purposeful, homogeneous group characteristics and sampling. Empirical data were collected using 24/7 participatory observations. The collected data were analyzed using a phenomenological–hermeneutical method: a naïve understanding, a structural analysis and a comprehensive understanding. The result shows that the onset of CB depends on whether the resident feels safe and is triggered by an excess or lack of stimuli. The excess or shortage of stimuli and whether and when it affects a person is personal. It depends on various factors, the person’s state and the time of day, the nature of the stimuli, familiarity, or strangeness is also a determining factor for the onset and progression of CB. The results can form an essential basis for developing soundscapes to make the PwD feel safe and reduce CB.</jats:p