University of Geneva

About: University of Geneva is a education organization based out in Geneva, Switzerland. It is known for research contribution in the topics: Population & Galaxy. The organization has 26887 authors who have published 65265 publications receiving 2931373 citations. The organization is also known as: Geneva University & Universite de Geneve.

The rise and fall of Hox gene clusters

Abstract: Although all bilaterian animals have a related set of Hox genes, the genomic organization of this gene complement comes in different flavors In some unrelated species, Hox genes are clustered; in others, they are not This indicates that the bilaterian ancestor had a clustered Hox gene family and that, subsequently, this genomic organization was either maintained or lost Remarkably, the tightest organization is found in vertebrates, raising the embarrassingly finalistic possibility that vertebrates have maintained best this ancestral configuration Alternatively, could they have co-evolved with an increased ;organization' of the Hox clusters, possibly linked to their genomic amplification, which would be at odds with our current perception of evolutionary mechanisms? When discussing the why's and how's of Hox gene clustering, we need to account for three points: the mechanisms of cluster evolution; the underlying biological constraints; and the developmental modes of the animals under consideration By integrating these parameters, general conclusions emerge that can help solve the aforementioned dilemma

Functional and Evolutionary Relationships Among Diverse Oxygenases

Abstract: Oxygenases that incorporate one or two atoms of dioxygen into substrates are found in many metabolic pathways In this article, representative oxygenases, principally those found in bacterial pathways for the degradation of hydrocarbons, are reviewed Monooxygenases, discussed in this chapter, incorporate one hydroxyl group into substrates In this reaction, two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation of NAD(P)H Dioxygenases catalyze the incorporation of two atoms of dioxygen into substrates Two types of dioxygenases, aromatic-ring dioxygenases and aromatic-ring-cleavage dioxygenases, are discussed The aromatic-ring dioxygenases incorporate two hydroxyl groups into aromatic substrates, and cis-diols are formed This reaction also requires NAD(P)H as an electron donor Aromatic-ring-cleavage dioxygenases incorporate two atoms of dioxygen into aromatic substrates, and the aromatic ring is cleaved This reaction does not require an external reductant All the oxygenases possess a cofactor, a transition metal, flavin or pteridine, that interacts with dioxygen The concerted reactions between dioxygen and carbon in organic compounds are spin forbidden The cofactor is used to overcome this restriction For the oxygenases that require the NAD(P)H cofactor, the enzyme reaction is separated into two steps, the oxidation of NAD(P)H to generate two reducing equivalents, and the hydroxylation of substrates Flavoprotein hydroxylases that catalyze the monohydroxylation of the aromatic ring carry out these two reactions on a single polypeptide chain In other oxygenases, the NAD(P)H oxidation and a hydroxylation reaction are catalyzed by two separate polypeptides that are linked by a short electron-transport chain Two reducing equivalents generated by the oxidation of NAD(P)H are transferred through the electron-transport chain to the cofactor on a hydroxylase component that they reduce Dioxygen couples with the reduced cofactor and subsequently hydroxylates substrates The electron-transport chains associated with oxygenases contain at least two redox centers The first redox center is usually a flavin, while the second is an iron-sulfur cluster The electron transport is initiated by a single two-electron transfer from NAD(P)H to a flavin, followed by two single-electron transfers from the flavin to an iron-sulfur cluster The primary sequences of many oxygenases have been determined, and according to their sequence similarities, the oxygenases can be grouped into several protein families Among proteins of the same family, the sequences in regions involved in cofactor binding are strongly conserved Local sequence similarities are also observed among oxygenases from different families, primarily in regions involved in cofactor binding

Device-independent quantum key distribution secure against collective attacks

Abstract: Device-independent quantum key distribution (DIQKD) represents a relaxation of the security assumptions made in usual quantum key distribution (QKD). As in usual QKD, the security of DIQKD follows from the laws of quantum physics, but contrary to usual QKD, it does not rely on any assumptions about the internal working of the quantum devices used in the protocol. In this paper, we present in detail the security proof for a DIQKD protocol introduced in Acin et al (2008 Phys. Rev. Lett. 98 230501). This proof exploits the full structure of quantum theory (as opposed to other proofs that exploit only the no-signaling principle), but only holds against collective attacks, where the eavesdropper is assumed to act on the quantum systems of the honest parties independently and identically in each round of the protocol (although she can act coherently on her systems at any time). The security of any DIQKD protocol necessarily relies on the violation of a Bell inequality. We discuss the issue of loopholes in Bell experiments in this context.

TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection.

Abstract: Cytotoxic T cells are essential mediators of protective immunity to viral infection and malignant tumours and are a key target of immunotherapy approaches. However, prolonged exposure to cognate antigens often attenuates the effector capacity of T cells and limits their therapeutic potential1-4. This process, known as T cell exhaustion or dysfunction1, is manifested by epigenetically enforced changes in gene regulation that reduce the expression of cytokines and effector molecules and upregulate the expression of inhibitory receptors such as programmed cell-death 1 (PD-1)5-8. The underlying molecular mechanisms that induce and stabilize the phenotypic and functional features of exhausted T cells remain poorly understood9-12. Here we report that the development and maintenance of populations of exhausted T cells in mice requires the thymocyte selection-associated high mobility group box (TOX) protein13-15. TOX is induced by high antigen stimulation of the T cell receptor and correlates with the presence of an exhausted phenotype during chronic infections with lymphocytic choriomeningitis virus in mice and hepatitis C virus in humans. Removal of its DNA-binding domain reduces the expression of PD-1 at the mRNA and protein level, augments the production of cytokines and results in a more polyfunctional T cell phenotype. T cells with this deletion initially mediate increased effector function and cause more severe immunopathology, but ultimately undergo a massive decline in their quantity, notably among the subset of TCF-1+ self-renewing T cells. Altogether, we show that TOX is a critical factor for the normal progression of T cell dysfunction and the maintenance of exhausted T cells during chronic infection, and provide a link between the suppression of effector function intrinsic to CD8 T cells and protection against immunopathology.