Acetylome in Human Fibroblasts From Parkinson's Disease Patients

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder. The pathogenesis of this disease is associated with gene and environmental factors. Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent genetic cause of familial and sporadic PD. Moreover, posttranslational modifications, including protein acetylation, are involved in the molecular mechanism of PD. Acetylation of lysine proteins is a dynamic process that is modulated in PD. In this descriptive study, we characterized the acetylated proteins and peptides in primary fibroblasts from idiopathic PD (IPD) and genetic PD harboring G2019S or R1441G LRRK2 mutations. Identified acetylated peptides are modulated between individuals' groups. Although acetylated nuclear proteins are the most represented in cells, they are hypoacetylated in IPD. Results display that the level of hyperacetylated and hypoacetylated peptides are, respectively, enhanced in genetic PD and in IPD cells

Imported Plasmodium falciparum malaria in HIV-infected patients: a report of two cases

As HIV becomes a chronic infection, an increasing number of HIV-infected patients are travelling to malaria-endemic areas. Association of malaria with HIV/AIDS can be clinically severe. Severe falciparum malaria is a medical emergency that is associated with a high mortality, even when treated in an Intensive Care Unit. This article describes two cases of HIV-positive patients, who returned from malaria-endemic areas and presented a parasitaemia > 5% of erythrocytes and clinical signs of severe falciparum malaria, both with > 350 CD4 cell count/μl, absence of chemoprophylaxis and successful response. Factors like drug interactions and the possible implication of anti-malarial therapy bioavailability are all especially interesting in HIV-malaria co-infections

Oxigenación con membrana extracorpórea en el paciente COVID-19: resultados del Registro Español ECMO-COVID de la Sociedad Española de Cirugía Cardiovascular y Endovascular (SECCE)

Background and aim: COVID-19 patients with severe heart or respiratory failure are potential candidates for extracorporeal membrane oxygenation (ECMO). Indications and management of these patients are unclear. Our aim is to describe the results of a prospective registry of COVID-19 patients treated with ECMO. Methods: An anonymous prospective registry of COVID-19 patients treated with veno-arterial (V-A) or veno-venous (V-V) ECMO was created on march 2020. Clinical, analytical and respiratory preimplantation variables, implantation data and post-implantation course data were recorded. The primary endpoint was all cause in-hospital mortality. Secondary events were functional recovery and the combined endpoint of mortality and functional recovery in patients followed at least 3 months after discharge. Results: Three hundred and sixty-six patients from 25 hospitals were analyzed, 347 V-V ECMO and 18 V-A ECMO patients (mean age 52.7 and 49.5 years respectively). Patients with V-V ECMO were more obese, had less frequently organ damage other than respiratory failure and needed less inotropic support; Thirty three percent of V-A ECMO and 34.9% of V-A ECMO were discharged (P = NS). Hospital mortality was non-significantly different, 56.2% versus 50.9% respectively, mainly during ECMO therapy and mostly due to multiorgan failure. Other 51 patients (14%) remained admitted. Mean follow-up was 196 +/- 101.7 days (95%CI: 170.8-221.6). After logistic regression, body weight (OR 0.967, 95%CI: 0.95-0.99, P = 0.004) and ECMO implantation in the own centre (OR 0.48, 95%CI: 0.27-0.88, P = 0.018) were protective for hospital mortality. Age (OR 1.063, 95%CI: 1.005-1.12, P = 0.032), arterial hypertension (3.593, 95%CI: 1.06-12.19, P = 0.04) and global (2.44, 95%CI: 0.27-0.88, P = 0.019), digestive (OR 4,23, 95%CI: 1.27-14.07, P = 0.019) and neurological (OR 4.66, 95%CI: 1.39-15.62, P = 0.013) complications during ECMO therapy were independent predictors of primary endpoint occurrence. Only the post-discharge day at follow-up was independent predictor of both secondary endpoints occurrence. Conclusions: Hospital survival of severely ill COVID-19 patients treated with ECMO is near 50%. Age, arterial hypertension and ECMO complications are predictors of hospital mortality, and body weight and implantation in the own centre are protective. Functional recovery is only predicted by the follow-up time after discharge. A more homogeneous management of these patients is warranted for clinical results and future research optimization. (C) 2022 Sociedad Espanola de Cirugia Cardiovascular y Endovascular. Published by Elsevier Espana, S.L.U

LA PRODUCCIÓN INFORMAL DE VIVIENDAS: CASO MARACAIBO, VENEZUELA

[EN]In housing production in Venezuela and particularly in Maracaibo, we can recognize two main sectors: the "formal" sector production carried out by prívate and national enterprises, and ttie "informal" sector, which produces tiouses in marginal áreas and uncontrolled suburbs in town. The production in this sector tías become larger ttian ttie formal one. In act, in Maracaibo more than 60% of population is living in these types of suburbs. Ttiese people tiave resolved tfieir tiousing need accordingly to their low income and outside of offer sector of formal production. Ttiis paper analyses the house from a physical point of view by studying the constructives components in reíation to the socioeconomical aspects of the families and their direct participation in building and financing their house. Four stages of the physical consolidation of housing in suburbs were distinguish. This contribution as an analytic description of the physical situation of housing in studied áreas, concluded giving some recommendations for the improvement of the informal process of housing production in Maracaibo.[ES]En la producción de viviendas en Maracaibo (Venezuela) existen dos sectores: el SECTOR FORMAL se refiere a la producción de la empresa privada más la producción estatal y el SECTOR INFORMAL que es la producción de viviendas en las áreas de barrios; la producción de este sector es mayor que la formal, llegando a ser el 60% de la población de Maracaibo. En Latinoamérica este fenómeno se presenta en la mayoría de las grandes ciudades. Este trabajo analiza la vivienda desde el punto de vista físico, relacionando los aspectos constructivos con los socioeconómicos, de participación en la construcción y del financiamiento. Se establecieron 4 etapas de consolidación de la vivienda de producción informal, caracterizando cada una de las etapas de acuerdo a los promedios y porcentajes obtenidos. Es un trabajo analítico-descriptivo cuya finalidad es conocer los patrones de consolidación de estas viviendas, con el objeto de realizar recomendaciones para el proceso y producción de la vivienda informal en Maracaibo.Peer reviewe

Additional file 3: of In silico approach to designing rational metagenomic libraries for functional studies

Families created based on HMMs and the corresponding proteins. (ZIP 37.3 mb

G2019S Mutation of LRRK2 Increases Autophagy via MEK/ERK Pathway

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder characterized by mitochondrial dysfunction, oxidative stress, and later neuronal death. Several genetics and environmental factors have been implicated in the {PD} pathogenesis. Mutations in leucine-rich repeat kinase 2 (LRRK2) are a major cause of familial parkinsonism, and the {G2019S} mutation of {LRRK2} is one of the most prevalent. The deregulation of autophagic process in nerve cells is thought to be a possible cause of PD. {G2019S} mutant fibroblasts exhibited higher autophagic activity that can trigger cell death. In this sense, {G2019S} mutant cells displayed increased apoptosis hallmarks and enough susceptibility to MPP+ (1-methyl-4-phenylpyridinium). {G2019S} {LRRK2} heightens the phosphorylation of MAPK/ERK kinases (MEK). The use of 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126) reduced the enhanced autophagy suggesting that the {G2019S} mutation induces autophagy via MEK/ERK pathway. Further, the inhibition of this exacerbated autophagy reduces the sensitivity remarked in {G2019S} mutant cells

Acetylome in Human Fibroblasts From Parkinson's Disease Patients

Parkinson's disease (PD) is a multifactorial neurodegenerative disorder. The pathogenesis of this disease is associated with gene and environmental factors. Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent genetic cause of familial and sporadic PD. Moreover, posttranslational modifications, including protein acetylation, are involved in the molecular mechanism of PD. Acetylation of lysine proteins is a dynamic process that is modulated in PD. In this descriptive study, we characterized the acetylated proteins and peptides in primary fibroblasts from idiopathic PD (IPD) and genetic PD harboring G2019S or R1441G LRRK2 mutations. Identified acetylated peptides are modulated between individuals' groups. Although acetylated nuclear proteins are the most represented in cells, they are hypoacetylated in IPD. Results display that the level of hyperacetylated and hypoacetylated peptides are, respectively, enhanced in genetic PD and in IPD cells

mRNA and protein dataset of autophagy markers (LC3 and p62) in several cell lines

We characterized the dynamics of autophagy in vitro using four different cell systems and analyzing markers widely used in this field, i.e. LC3 (microtubule-associated protein 1 light chain 3; protein recruited from the cytosol (LC3-I) to the autophagosomal membrane where it is lipidated (LC3-II)) and p62/SQSTM1 (adaptor protein that serves as a link between LC3 and ubiquitinated substrates), (Klionsky et al., 2016) [1]. Data provided include analyses of protein levels of LC3 and p62 by Western-blotting and endogenous immunofluorescence experiments, but also p62 mRNA levels obtained by quantitative PCR (qPCR). To monitor the turnover of these autophagy markers and, thus, measure the flux of this pathway, cells were under starvation conditions and/or treated with bafilomycin A1 (Baf. A1) to block fusion of autophagosomes with lysosomes. Keywords: Autophagy, LC3, p62, Western-blo

PINK1 deficiency enhances autophagy and mitophagy induction

Parkinson's disease (PD) is a neurodegenerative disorder with poorly understood etiology. Increasing evidence suggests that age-dependent compromise of the maintenance of mitochondrial function is a key risk factor. Several proteins encoded by PD-related genes are associated with mitochondria including PTEN-induced putative kinase 1 (PINK1), which was first identified as a gene that is upregulated by PTEN. Loss-of-function PINK1 mutations induce mitochondrial dysfunction and, ultimately, neuronal cell death. To mitigate the negative effects of altered cellular functions cells possess a degradation mechanism called autophagy for recycling damaged components; selective elimination of dysfunctional mitochondria by autophagy is termed mitophagy. Our study indicates that autophagy and mitophagy are upregulated in PINK1-deficient cells, and is the first report to demonstrate efficient fluxes by one-step analysis. We propose that autophagy is induced to maintain cellular homeostasis under conditions of non-regulated mitochondrial quality control