Evidence-informed policy for tackling adverse climate change effects on health: Linking regional and global assessments of science to catalyse action.

Robin Fears and co-authors discuss evidence-informed regional and global policy responses to health impacts of climate change.

Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses.

While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS-dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis.

European Academies Advise on Gain-of-Function Studies in Influenza Virus Research.

Gain-of-function (GoF) studies to understand factors affecting transmissibility of potentially pandemic pathogens are controversial. The European Academies Science Advisory Council (EASAC) recently published consensus recommendations relating to GoF research review and management on self-regulation and harmonization; bioethical considerations; benefit-risk assessment; biosafety, and biosecurity advisory options; and publication of sensitive information. A layered approach to integration of responsibilities must include conforming to the stringent rules and guidance already existing. Further commitment is essential to extend the debate on issues worldwide.

Celebrating Achim Trebst's 80th birthday.

At the invitation of Govindjee, we reprint here the English translation of the letter, in German, that we sent, on behalf of the Senate and the Presidium as well as the members of the German Academy of Sciences Leopoldina, from Halle (Saale), to Professor Dr. Dr. h.c.mult. Achim Trebst on his 80th birthday. The original of this letter written in German will appear in Jahrbuch 2009, Deutsche Akademie der Naturforscher Leopoldina, Halle (Saale), Wissenschaftliche Verlagsgesellschaft mbH Stuttgart.

Disruption of excitatory amino acid transporters in brains of SIV-infected rhesus macaques is associated with microglia activation.

Glutamate-mediated neurodysfunction in human immunodeficiency virus (HIV) infection has been primarily suggested by in vitro studies. The regulation of glutamatergic neurotransmission in inflammation is a complex interaction between activation of immune mediators and adaptive changes in the functional elements of the glutamatergic synapse. We have used simian immunodeficiency virus (SIV)-infected macaques to answer the questions (i) whether perturbation of glutamate neurotransmission is evident during progression of immunodeficiency disease and (ii) what are the mechanisms underlying this impairment. Disease progression in SIV-infected macaques both in the periphery and in the brain was documented by clinical and general pathological examination, plasma and brain viral RNA load, T-cell analysis and brain histopathology. We report for the first time, disruption of excitatory amino acid transporters (EAATs), the cardinal glutamate clearing system, during SIV infection and a dramatic loss of EAATs associated with development of rapid acquired immunodeficiency syndrome (AIDS). EAATs impairment was correlated with activation status of microglia. Our data support the glutamate hypothesis for the development of HIV dementia and suggest that the pathogenetic mechanism for the neurodysfunction is the impairment of glutamate clearing which occurs in the stage of AIDS and which is associated with activated microglia.

Memantine upregulates BDNF and prevents dopamine deficits in SIV-infected macaques: a novel pharmacological action of memantine.

N-methyl-D-aspartate (NMDA) receptor activation is involved in the pathogenetic cascades of neurodegenerative disorders including human immunodeficiency virus (HIV) dementia. Memantine, an uncompetitive NMDA receptor antagonist, which has been recently approved for the treatment of Alzheimer's disease, is being discussed as a potential adjunctive therapeutic substance for HIV dementia. We used simian immunodeficiency virus-infected rhesus macaques to assess the effects of memantine on brain dysfunction and brain pathology within 3-5 months after initial infection during early asymptomatic stage of disease. We had shown previously that within this time frame, marked changes were evident in the dopaminergic systems. Memantine was administered two weeks post infection, at peak viremia, in order to prevent early NMDA receptor activation due to immune mediators. We found that memantine prevented onset of dopamine deficits in the brains of SIV-infected macaques, without affecting early brain pathology or peripheral course of infection. Memantine specifically upregulated mRNA and protein expression of the neurotrophic factor brain-derived neurotrophic factor (BDNF), suggesting that the protective effect of memantine on dopamine function may be mechanistically remote from NMDA receptor antagonism. This novel pharmacological action of memantine may also be relevant for other neurodegenerative disorders and supports the involvement of neurotrophic factors in adult brain neuroprotection.

How should the applications of genome editing be assessed and regulated?

An EASAC working group on genome editing recommends that regulators should focus on specific applications of these new techniques rather than attempting to regulate genome editing itself as a new technology.

Regulation of gene expression in lymphocytes and antigen-presenting cells by measles virus: consequences for immunomodulation.

Acute measles, a well known disease usually contracted during early childhood, is still the major cause of vaccine-preventable infant deaths worldwide. There are about 40 million cases of acute measles per year, with more than one million cases of infant death as a consequence of measles. These are mainly due to opportunistic infections which develop on the basis of a generalized suppression of the cellular immunity in the course and after the acute disease. Lymphopenia, a general proliferative unresponsiveness of T cells ex vivo and cytokine imbalance, are considered as major hallmarks of measles virus (MV) induced immunosuppression. These findings are compatible with modulation of T cell responses by viral interference with professional antigen-presenting cells such as dendritic cells or direct effects on T cells by suppression of survival or proliferation signals. In vitro, MV interaction causes a variety of effects on dendritic cells, including maturation and loss of their allostimulatory functions. Whether there is an additional impact on the quality of T cell responses is unknown as yet. It is clear, however, that surface interaction of lymphocytes with the MV glycoprotein complex is necessary and sufficient to induce a state of proliferative unresponsiveness in T cells. This surface contact mediated signal essentially interferes with the propagation of the interleukin 2 receptor signal by blocking the activation of the protein kinase B, also called Akt kinase, both in vitro and after experimental infection.

What next for gain-of-function research in Europe?

A working group on gain-of-function research set up by the European Academies Science Advisory Council (EASAC) has emphasised the importance of ensuring that the necessary safeguards and policies are in place.