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Clinically relevant immune responses against Cytomegalovirus : implications for precision medicine
(2019)
Immune responses to human cytomegalovirus (CMV) can be used to assess immune fitness in an individual. Further to its clinical significance in posttransplantation settings, emerging clinical and translational studies provide examples of immune correlates of protection pertaining to anti-CMV immune responses in the context of cancer or infectious diseases, e.g., tuberculosis. In this viewpoint, we provide a brief overview about CMV-directed immune reactivity and immune fitness in a clinical context and incorporate some of our own findings obtained from peripheral blood or tumour-infiltrating lymphocytes (TIL) from patients with advanced cancer. Observations in patients with solid cancers whose lesions contain both CMV and tumour antigen-specific T-cell subsets are highlighted, due to a possible CMV-associated "bystander" effect in amplifying local inflammation and subsequent tumour rejection. The role of tumour-associated antibodies recognising diverse CMV-derived epitopes is also discussed in light of anti-cancer immune responses. We discuss here the use of anti-CMV immune responses as a theranostic tool—combining immunodiagnostics with a personalised therapeutic potential—to improve treatment outcomes in oncological indications.
Fragments mycologiques
(1848)
Background: Pythium ultimum (P. ultimum) is a ubiquitous oomycete plant pathogen responsible for a variety of diseases on a broad range of crop and ornamental species. Results: The P. ultimum genome (42.8 Mb) encodes 15,290 genes and has extensive sequence similarity and synteny with related Phytophthora species, including the potato blight pathogen Phytophthora infestans. Whole transcriptome sequencing revealed expression of 86% of genes, with detectable differential expression of suites of genes under abiotic stress and in the presence of a host. The predicted proteome includes a large repertoire of proteins involved in plant pathogen interactions although surprisingly, the P. ultimum genome does not encode any classical RXLR effectors and relatively few Crinkler genes in comparison to related phytopathogenic oomycetes. A lower number of enzymes involved in carbohydrate metabolism were present compared to Phytophthora species, with the notable absence of cutinases, suggesting a significant difference in virulence mechanisms between P. ultimum and more host specific oomycete species. Although we observed a high degree of orthology with Phytophthora genomes, there were novel features of the P. ultimum proteome including an expansion of genes involved in proteolysis and genes unique to Pythium. We identified a small gene family of cadherins, proteins involved in cell adhesion, the first report in a genome outside the metazoans. Conclusions: Access to the P. ultimum genome has revealed not only core pathogenic mechanisms within the oomycetes but also lineage specific genes associated with the alternative virulence and lifestyles found within the pythiaceous lineages compared to the Peronosporaceae.
We present a systematic study on the influence of spatial correlations between the proton constituents, in our case gluonic hot spots, their size and their number on the symmetric cumulant SC(2,3), at the eccentricity level, within a Monte Carlo Glauber framework [J.L. Albacete, H. Petersen, A. Soto-Ontoso, Symmetric cumulants as a probe of the proton substructure at LHC energies, Phys. Lett. B778 (2018) 128–136. arXiv:1707.05592, doi:10.1016/j.physletb.2018.01.011]. When modeling the proton as composed by 3 gluonic hot spots, the most common assumption in the literature, we find that the inclusion of spatial correlations is indispensable to reproduce the negative sign of SC(2,3) in the highest centrality bins as dictated by data. Further, the subtle interplay between the different scales of the problem is discussed. To conclude, the possibility of feeding a 2+1D viscous hydrodynamic simulation with our entropy profiles is exposed.
We present a systematic study of the normalized symmetric cumulants, NSC(n,m), at the eccentricity level in proton-proton interactions at within a wounded hot spot approach. We focus our attention on the influence of spatial correlations between the proton constituents, in our case gluonic hot spots, on this observable. We notice that the presence of short-range repulsive correlations between the hot spots systematically decreases the values of and in mid- to ultra-central collisions while increases them in peripheral interactions. In the case of we find that, as suggested by data, an anti-correlation of and in ultra-central collisions, i.e. , is possible within the correlated scenario while it never occurs without correlations when the number of gluonic hot spots is set to three. We attribute this fact to the decisive role of correlations on enlarging the probability of interaction topologies that reduce the value of and, eventually, make it negative. Further, we explore the dependence of our conclusions on the number of hot spots, the values of the hot spot radius and the repulsive core distance. Our results add evidence to the idea that considering spatial correlations between the subnucleonic degrees of freedom of the proton may have a strong impact on the initial state properties of proton-proton interactions [1].
In this work, largely based on [J. L. Albacete, A. Soto-Ontoso, Hot spots and the hollowness of proton-proton interactions at high energies, arXiv:1605.09176; J. L. Albacete, H. Petersen, A. Soto-Ontoso, Correlated wounded hot spots in proton-proton interactions, arXiv:1612.06274], we present a novel initial state geometry for proton-proton interactions. We rely on gluonic hot spots as effective degrees of freedom whose transverse positions inside the proton are correlated. We explore the impact of these non-trivial spatial correlations on the eccentricity and triangularity of the system following a Monte Carlo Glauber approach.
Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.
Die Biopolitik ist in den letzten Jahrzehnten zu einem grundlegenden Studienbereich für das Verständnis unserer politischen Modernität und zu einem wertvollen Instrument für die Analyse von literarischen Texten geworden. In der aktuellen Literatur zu Günter Grass' Roman "Die Blechtrommel" (1959) findet man jedoch keine ausführliche Studie, die eine biopolitische Perspektive als hermeneutische Annäherungsmethode einnimmt. Eine Analyse von "Die Blechtrommel" vor dem theoretischen Rahmen der Biopolitik ist aber für eine umfassende Lektüre des Textes notwendig, wie im Folgenden belegt wird. [...] Um sich der nationalsozialistischen Biopolitik zu widersetzen und bürgerliche Rationalitätsparadigmen zu untergraben, lässt Grass verschiedene Facetten der Populärkultur (insbesondere Volks- und Kunstmärchen), die der Nationalsozialismus entweder unterdrückte oder für seine Ideologie manipulierte, wieder aufleben. Strukturell und inhaltlich verbindet Grass' Roman die Verfolgung 'entarteter' Kunst mit der Verfolgung und Ausrottung 'entarteter' Menschen, für die der verfolgte Zwerg Oskar zur zentralen Metapher und Stimme wird. Der groteske Körper Oskars bildet in seinem Überleben und subversiven Praktiken gegen die diktatorische Autorität einen alternativen Diskurs gegen NS-Körperideale, die vor allem von Rezeptionen der klassischen Kunst beeinflusst waren. Durch eine Reihe intertextueller Bezüge zur Märchen-Tradition und seine Ästhetik des Grotesken erschafft der Roman eine irrationale Gegenkultur, die sich dem zerstörenden Rationalismus der Nazi-Biopolitik und der Kontinuität dieses Eugenik Gedankens im Nachkriegsdeutschland entgegenstellt, wobei gleichzeitig die Absurdität der Stunde Null entlarvt wird.
Sound discrimination is essential in many species for communicating and foraging. Bats, for example, use sounds for echolocation and communication. In the bat auditory cortex there are neurons that process both sound categories, but how these neurons respond to acoustic transitions, that is, echolocation streams followed by a communication sound, remains unknown. Here, we show that the acoustic context, a leading sound sequence followed by a target sound, changes neuronal discriminability of echolocation versus communication calls in the cortex of awake bats of both sexes. Nonselective neurons that fire equally well to both echolocation and communication calls in the absence of context become category selective when leading context is present. On the contrary, neurons that prefer communication sounds in the absence of context turn into nonselective ones when context is added. The presence of context leads to an overall response suppression, but the strength of this suppression is stimulus specific. Suppression is strongest when context and target sounds belong to the same category, e.g.,echolocation followed by echolocation. A neuron model of stimulus-specific adaptation replicated our results in silico The model predicts selectivity to communication and echolocation sounds in the inputs arriving to the auditory cortex, as well as two forms of adaptation, presynaptic frequency-specific adaptation acting in cortical inputs and stimulus-unspecific postsynaptic adaptation. In addition, the model predicted that context effects can last up to 1.5 s after context offset and that synaptic inputs tuned to low-frequency sounds (communication signals) have the shortest decay constant of presynaptic adaptation.SIGNIFICANCE STATEMENT We studied cortical responses to isolated calls and call mixtures in awake bats and show that (1) two neuronal populations coexist in the bat cortex, including neurons that discriminate social from echolocation sounds well and neurons that are equally driven by these two ethologically different sound types; (2) acoustic context (i.e., other natural sounds preceding the target sound) affects natural sound selectivity in a manner that could not be predicted based on responses to isolated sounds; and (3) a computational model similar to those used for explaining stimulus-specific adaptation in rodents can account for the responses observed in the bat cortex to natural sounds. This model depends on segregated feedforward inputs, synaptic depression, and postsynaptic neuronal adaptation.