We’re not all equal in the face of the coronavirus

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Are there differences in immunity to the SARS-CoV-2 coronavirus between populations from different geographic regions? Part of the answer to this question is to be found in the genomes of these groups of people and, more specifically, in the HLA genes responsible for the adaptive immune system. These genes are special in that they often differ between individuals. Thousands of possible variants (or alleles) have been identified, and not all of them are equally effective in fighting a new virus. The frequency of these alleles varies from one population to another due to past migrations and their adaptation to different environments. Alicia Sanchez-Mazas group,  – working in collaboration with the Max Planck Institute in Jena (Germany) and the University of Adelaide (Australia) – has pinpointed the HLA variants that are potentially the most effective against seven viruses, including the new coronavirus. They have also brought to light significant differences between populations.

This article was published in HLA on May 31st, 2020.

Press release from UNIGE.

 

This study is also covered by other media :

Des populations inégales face au coronavirus Avis d’Expert, RTS, 11.06.2020

Les humains pas tous égaux face au coronavirus Le Temps, 11.06.2020

UNIGE: les humains pas tous égaux face au… Radio Lac, 11.06.2020

Différences d’immunité face au coronavirus choisir.ch / Choisir Revue Culturelle Online, 10.06.2020

Les humains pas tous égaux face au coronavirus L’Avenir.net, 11.06.2020

Coronavirus: les humains ne sont pas tous… Sudinfo.be, 11.06.2020

We’re not all equal in face of coronavirus MirageNewsCom / Mirage News, 11.06.2020

Our immune systems are not all equal in the… Technology Networks, 11.06.2020

A history of the medical mask and the rise of throwaway culture

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What are the causes of the shortage of face masks during the COVID-19 pandemic? Research by Bruno J. Strasser of the University of Geneva and Thomas Schlich of McGill University on the origin of the medical mask answers this question from a historical perspective.

The authors show that masks were developed at the end of the 19th century to prevent surgeons from infecting their patients. But it was during the influenza pandemic of 1918-1919 that their use became widespread to protect against infectious people. All masks, made of fabric and metal, were reusable. In the 1960s, the industry developed and vigorously promoted disposable masks. Experimental studies showed that they were no more effective than reusable masks. However, they eventually replaced reusable masks, creating a dependence on a constant supply. The recent shortage of masks, with sometimes tragic consequences for medical workers, shows the cost of this historic choice.

This article was published in The Lancet, on May 22nd 2020.

On the same topic:

” L’élimination des masques réutilisables est un choix historique discutable” : Interview from Bruno Strasser in Le Monde, published on May 25th 2020.

“2020, année de la science citoyenne?” : Le grand débat with Bruno Strasser on RTS on May 25th 2020.

“Et si l’erreur c’était de vouloir des masques jetables”: Emission radio Superfail on France Culture, June 1st 2020.

The CzcCBA Efflux System Requires the CadA P-Type ATPase for Timely Expression Upon Zinc Excess in Pseudomonas aeruginosa

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Zinc (Zn) is a trace element essential for life but can be toxic if present in excess. While cells have import systems to guarantee a vital Zn intracellular concentration, they also rely on export systems to avoid lethal Zn overload. In particular, the opportunistic pathogen Pseudomonas aeruginosa possesses four Zn export systems: CadA, CzcCBA, CzcD, and YiiP. In this work, Karl Perron’s group compares the importance for bacterial survival of each export system at high Zn concentrations and shows that the P-type ATPase CadA, and the efflux pump CzcCBA are the main efflux systems affecting the bacterium tolerance to Zn.

The present data show that the fast responsiveness of cadA to Zn excess is due to its transcriptional activator, CadR, which is constitutively present on its promoter and promptly activating cadA gene expression upon Zn binding. Finally, they observed an induction of cadA and czcCBA efflux systems upon phagocytosis of P. aeruginosa by macrophages, in which a toxic metal boost is discharged into the phagolysosome to intoxicate microbes. Importantly, they demonstrated that the regulatory link between induction of the CzcCBA system and the repression of the OprD porin responsible for carbapenem antibiotic resistance, is maintained in the macrophage environment.

This study was published in Frontiers in Microbiology on the 15th May 2020.

Article

UVR8-mediated inhibition of shade avoidance involves HFR1 stabilization in Arabidopsis

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Sun-loving plants perceive the proximity of potential light-competing neighboring plants as a reduction in the red:far-red ratio (R:FR), which elicits a suite of responses called the “shade avoidance syndrome” (SAS). Changes in R:FR are primarily perceived by phytochrome B (phyB), whereas UV-B perceived by UV RESISTANCE LOCUS 8 (UVR8) elicits opposing responses to provide a counterbalance to SAS, including reduced shade-induced hypocotyl and petiole elongation.

Here Roman Ulm’s group show at the genome-wide level that UVR8 broadly suppresses shade-induced gene expression. A subset of this gene regulation is dependent on the UVR8-stabilized atypical bHLH transcription regulator LONG HYPOCOTYL IN FAR-RED 1 (HFR1), which functions in part redundantly with PHYTOCHROME INTERACTING FACTOR 3-LIKE 1 (PIL1). In parallel, UVR8 signaling decreases protein levels of the key positive regulators of SAS, namely the bHLH transcription factors PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and PIF5, in a COP1-dependent but HFR1-independent manner. We propose that UV-B antagonizes SAS via two mechanisms: degradation of PIF4 and PIF5, and HFR1- and PIL1-mediated inhibition of PIF4 and PIF5 function. This work highlights the importance of typical and atypical bHLH transcription regulators for the integration of light signals from different photoreceptors and provides further mechanistic insight into the crosstalk of UVR8 signaling and SAS.

This study was published in PLOS Genetics on the 11th May 2020.

Article

Fine chromatin-driven mechanism of transcription interference by antisense noncoding transcription

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While the spotlight has been for a long time on coding transcription, it turns out that noncoding transcription is largely predominant in a eukaryotic cell. This pervasiveness of noncoding transcription might have functional consequences: many noncoding transcripts overlap with promoter regions of coding genes. This might lead to the repression of the corresponding coding gene in a mechanism named transcription interference. It was known that this mechanism involves chromatin regulation, however the precise sequence of events triggering transcription interference was not yet defined.

The laboratory of Françoise Stutz proposes a fine mechanism of transcription interference by antisense noncoding transcription. Jatinder Kaur Gill, Julien Soudet and colleagues show that the induction of antisense noncoding transcription through the promoter region of the associated coding gene results in nucleosome repositioning. This leads to a decrease of transcription initiation of the coding gene. Based on highly resolutive sequencing technics, this study also shows that some histone modifications induce a differential positioning of nucleosomes. At last, the authors conclude that 1/5 of the coding genes are regulated through a process compatible with their model.

Considering the conservation of the involved factors, it appears likely that the regulation of many human coding genes may depend on the mechanism proposed in this publication.

This study was published in Cell Reports on the 5th May 2020.

Article

Life Sciences PhD School: Call for applications!

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Submit your application for the Summer Call of the PhD School of Life Sciences at the Faculties of Medicine and Science – University of Geneva. The application deadline is Apr 15th, 2020.

PhD positions will be available in six innovative programmes:

• Biomedical Sciences
• Ecology and Evolution
• Genomics and Digital Health
• Molecular Biosciences
• Pharmaceutical Sciences
• Physics of Biology

For further information please visit: https://lifesciencesphd.unige.ch

Molecular mechanism for the recognition of sequence-divergent CIF peptides by the plant receptor kinases GSO1/SGN3 and GSO2

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The plant leucine-rich repeat receptor kinases GSO1/SGN3 and its peptide ligands CIF1 and CIF2 are essential for the formation of the Casparian strip. The Hothorn group from the Department of Botany and Plant Biology, in collaboration with the Geldner group from UNIL, has now uncovered in molecular detail how the SCHENGEN 3 receptor complex tightly binds CIF1 and CIF2.

Crystal structure of the GSO1/SGN3–CIF complex reveals a binding pocket for sulfotyrosine and extended back-bone interactions with CIF2. Structure-guided sequence analysis allowed to uncover previously uncharacterized CIF peptides conserved among higher plants. Quantitative binding assays with known and novel CIFs suggest that the homologous LRR-RKs GSO1/SGN3 and GSO2 have evolved unique peptide binding properties to control different developmental processes. A quantitative biochemical interaction screen, a CIF peptide antagonist and genetic analyses together implicate SERK proteins as essential coreceptor kinases required for GSO1/SGN3 and GSO2 receptor activation.

This work provides a mechanistic framework for the recognition of sequence-divergent peptide hormones in plants and was published in PNAS on January 21, 2020.

Article

Toxoplasmosis rids its host of all fear

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Toxoplasma gondii is a neurotropic parasite that infects all warm-blooded animals, including humans. Its objective is to reach the intestines of felids, the definitive host in which it reproduces sexually. To do so, the parasite first infects mice and drastically alters their behaviour. The natural aversion of mice toward cats is decreased – a phenomenon called fatal attraction – making them easy preys.

Using a set of complementary behavioral tests, Ivan Rodriguez and Dominique Soldati-Favre groups showed that T. gondii lowers general anxiety in infected mice, increases explorative behaviors, and surprisingly alters predator aversion without selectivity toward felids.

Their findings refute the myth of a selective loss of cat fear in T. gondii-infected mice and point toward widespread immune-related alterations of behaviors.

The study was published in Cell Reports on January 14, 2020.

Article

A novel protease contributes to the repair of DNA-protein crosslinks

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DNA-protein crosslinks (DPCs) are formed in the course of normal cell metabolism. However, their prolonged persistence can be extremely toxic, cause genome instability and promote diseases such as cancer.

The Stutz laboratory, together with the Kornmann (University of Oxford) and Loewith groups,describes a new mechanism required for the efficient DPC disassembly. Through a yeast genetic screen, Serbyn and collaborators identified the enigmatic Ddi1 protease as a new candidate degrading the protein moiety of DPCs. The authors show that Ddi1 helps to resolve a broad variety of DNA-protein crosslinks and functions independently of the known pathways involved in proteolytic DPC elimination.

Loss of Ddi1 sensitizes cells to several compounds that trap DPCs, including approved anti-cancer drugs. The latter provides novel insights into the putative mechanisms of drug resistance often observed in therapeutics.

The study was published in Molecular Cell on January 2, 2020.

Article

The elephant’s trunk will inspire a revolutionary robot

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An international team, including the group of Professor Michel Milinkovitch, will analyse the African elephant’s trunk, and its exceptional agility and versatility, to create a new generation of manipulative robots capable of operating in unstable environments, adapting quickly to unexpected situations and performing a multitude of concrete tasks.

Read the press release