Cellular senescence at the crossroads of inflammation and Alzheimer's disease

Aging is a key risk factor for Alzheimer's disease (AD), but the reasons for this association are not well understood. Senescent cells accumulate in aged tissues and have been shown to play causal roles in age-related pathologies through their proinflammatory secretome. The question arises whether senescence-induced inflammation might contribute to AD and bridge the gap between aging and AD. Here, we highlight the role of cellular senescence as a driver of the aging phenotype, and discuss the current evidence that connects senescence with AD and neurodegeneration

Aplicación de la genética e innovaciones biotecnológicas en el aprovechamiento sostenible de los recursos del mar

Las Ciencias del Mar tienen como objetivo central poder entender los procesos físicos y biológicos que ocurren en este ambiente. La información obtenida es el insumo básico para el diagnóstico, planificación y uso sostenible de los recursos del mar para el beneficio humano, en el presente y el futuro. Para efectos prácticos, los organismos vivos son genotipos que se expresan en un determinado ambiente, y si bien desde la primera mitad del siglo pasado conocemos los mecanismos básicos de la transmisión hereditaria, no es sino hasta la segunda mitad del siglo pasado que ha sido posible acceder directamente al genoma de los organismos

Phenomenology of a scotogenic neutrino mass model at 3-loops

By extending the minimal scotogenic model with a spontaneously broken global symmetry $U(1)'$ and a preserved $\mathbb{Z}_2$ symmetry, we build a seesaw model for generating neutrino masses at three-loop level. The new particles have masses at the TeV scale and relatively large Yukawa couplings, which leads to sizable rates for charged lepton flavor violation processes, well within future experimental reach. The model is able to successfully explain the $W$ mass anomaly and provides a viable fermionic or scalar dark matter candidate, while satisfying all current constraints imposed by neutrinoless double-beta decay, charged-lepton flavor violation, and electroweak precision observables.Comment: 4 pages, 3 figures. Presented at the XVIII International Conference on Topics in Astroparticle and Underground Physics (TAUP 2023

New distance measures for classifying X-ray astronomy data into stellar classes

The classification of the X-ray sources into classes (such as extragalactic sources, background stars, ...) is an essential task in astronomy. Typically, one of the classes corresponds to extragalactic radiation, whose photon emission behaviour is well characterized by a homogeneous Poisson process. We propose to use normalized versions of the Wasserstein and Zolotarev distances to quantify the deviation of the distribution of photon interarrival times from the exponential class. Our main motivation is the analysis of a massive dataset from X-ray astronomy obtained by the Chandra Orion Ultradeep Project (COUP). This project yielded a large catalog of 1616 X-ray cosmic sources in the Orion Nebula region, with their series of photon arrival times and associated energies. We consider the plug-in estimators of these metrics, determine their asymptotic distributions, and illustrate their finite-sample performance with a Monte Carlo study. We estimate these metrics for each COUP source from three different classes. We conclude that our proposal provides a striking amount of information on the nature of the photon emitting sources. Further, these variables have the ability to identify X-ray sources wrongly catalogued before. As an appealing conclusion, we show that some sources, previously classified as extragalactic emissions, have a much higher probability of being young stars in Orion Nebula.Comment: 29 page

Epithelial immune activation and intracellular invasion by non-typeable Haemophilus influenzae

Type-2 low asthma affects 30-50% of people with severe asthma and includes a phenotype characterized by sputum neutrophilia and resistance to corticosteroids. Airways inflammation in type-2 low asthma or COPD is potentially driven by persistent bacterial colonization of the lower airways by bacteria such as non-encapsulated Haemophilus influenzae (NTHi). Although pathogenic in the lower airways, NTHi is a commensal of the upper airways. It is not known to what extent these strains can invade airway epithelial cells, persist intracellularly and activate epithelial cell production of proinflammatory cytokines, and how this differs between the upper and lower airways. We studied NTHi infection of primary human bronchial epithelial cells (PBECs), primary nasal epithelial cells (NECs) and epithelial cell lines from upper and lower airways. NTHi strains differed in propensity for intracellular and paracellular invasion. We found NTHi was internalized within PBECs at 6 h, but live intracellular infection did not persist at 24 h. Confocal microscopy and flow cytometry showed NTHi infected secretory, ciliated and basal PBECs. Infection of PBECs led to induction of CXCL8, interleukin (IL)-1β, IL-6 and TNF. The magnitude of cytokine induction was independent of the degree of intracellular invasion, either by differing strains or by cytochalasin D inhibition of endocytosis, with the exception of the inflammasome-induced mediator IL-1β. NTHi-induced activation of TLR2/4, NOD1/2 and NLR inflammasome pathways was significantly stronger in NECs than in PBECs. These data suggest that NTHi is internalized transiently by airway epithelial cells and has capacity to drive inflammation in airway epithelial cells

Global metabolomic profiling of uterine leiomyomas

Background: Uterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas. Methods: We performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy. Results: A total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the FH subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the FH subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for FH deficiency. In contrast, leiomyomas of the MED12 subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data. Conclusions: The study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.Peer reviewe