Sudden unexpected death in Parkinson's disease: Insights from clinical practice

Classified as the second most common neurodegenerative disorder associated with aging after Alzheimer's disease, Parkinson's disease (PD) is the most common movement disorder. In the last decade, despite advances in treatment, mortality rates linked with PD continued to reach significant figures. Available studies have shown that compared with healthy controls, patients with PD are accompanied by high rates of premature death. This is usually caused by factors such as pneumonia and cerebrovascular and cardiovascular diseases. Recently, it has been demonstrated that a significant proportion of patients with PD die suddenly. This is referred to as a sudden and unexpected death in PD (SUDPAR). Here, we focus on the magnitude of SUDPAR. Finally, it is important to learn more about SUDPAR for the implementation of effective prevention strategies

Nonatobase: A Database For Polychaeta (annelida) From The Southwestern Atlantic Ocean.

Networks can greatly advance data sharing attitudes by providing organized and useful data sets on marine biodiversity in a friendly and shared scientific environment. NONATObase, the interactive database on polychaetes presented herein, will provide new macroecological and taxonomic insights of the Southwestern Atlantic region. The database was developed by the NONATO network, a team of South American researchers, who integrated available information on polychaetes from between 5°N and 80°S in the Atlantic Ocean and near the Antarctic. The guiding principle of the database is to keep free and open access to data based on partnerships. Its architecture consists of a relational database integrated in the MySQL and PHP framework. Its web application allows access to the data from three different directions: species (qualitative data), abundance (quantitative data) and data set (reference data). The database has built-in functionality, such as the filter of data on user-defined taxonomic levels, characteristics of site, sample, sampler, and mesh size used. Considering that there are still many taxonomic issues related to poorly known regional fauna, a scientific committee was created to work out consistent solutions to current misidentifications and equivocal taxonomy status of some species. Expertise from this committee will be incorporated by NONATObase continually. The use of quantitative data was possible by standardization of a sample unit. All data, maps of distribution and references from a data set or a specified query can be visualized and exported to a commonly used data format in statistical analysis or reference manager software. The NONATO network has initialized with NONATObase, a valuable resource for marine ecologists and taxonomists. The database is expected to grow in functionality as it comes in useful, particularly regarding the challenges of dealing with molecular genetic data and tools to assess the effects of global environment change. Database URL: http://nonatobase.ufsc.br/.2014bau00

Cell division protein FtsK coordinates bacterial chromosome segregation and daughter cell separation in Staphylococcus aureus

Funding Information: We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center Tübingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC‐2017‐CoG‐771709 (to MGP), by national funds through FCT– Fundação para a Ciência e a Tecnologia, PTDC/BIA‐MIC/6982/2020 (to HV); PTDC/BIA‐PLA/3432/2012 (to SRF); FCT through MOSTMICRO‐ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and FCT fellowship SFRH/BD/147052/2019 (to BMS); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska‐Curie grant agreement No 839596 (to SS) and by the European Molecular Biology Organization through award ALTF 673‐2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com . Funding Information: We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center Tübingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC-2017-CoG-771709 (to MGP), by national funds through FCT– Fundação para a Ciência e a Tecnologia, PTDC/BIA-MIC/6982/2020 (to HV); PTDC/BIA-PLA/3432/2012 (to SRF); FCT through MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and FCT fellowship SFRH/BD/147052/2019 (to BMS); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 839596 (to SS) and by the European Molecular Biology Organization through award ALTF 673-2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com. Publisher Copyright: © 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.Unregulated cell cycle progression may have lethal consequences and therefore, bacteria have various mechanisms in place for the precise spatiotemporal control of cell cycle events. We have uncovered a new link between chromosome replication/segregation and splitting of the division septum. We show that the DNA translocase domain-containing divisome protein FtsK regulates cellular levels of a peptidoglycan hydrolase Sle1, which is involved in cell separation in the bacterial pathogen Staphylococcus aureus. FtsK interacts with a chaperone (trigger factor, TF) and establishes a FtsK-dependent TF concentration gradient that is higher in the septal region. Trigger factor binds Sle1 and promotes its preferential export at the septal region, while also preventing Sle1 degradation by the ClpXP proteolytic machinery. Upon conditions that lead to paused septum synthesis, such as DNA damage or impaired DNA replication/segregation, TF gradient is dissipated and Sle1 levels are reduced, thus halting premature septum splitting.publishersversionpublishe

Lipid droplet levels vary heterogeneously in response to simulated gastrointestinal stresses in different probiotic Saccharomyces cerevisiae strains

AbstractTo exert their therapeutic action, probiotic Saccharomyces cerevisiae strains must survive harsh digestive environments. Lipid droplets accumulate in cells which undergo stress-inducing situations, supposedly having a protective role. We assessed lipid droplet levels, either naturally accumulated or induced in response to digestive challenges, of probiotic strains S. boulardii, S. cerevisiae A-905, S. cerevisiae Sc47 and S. cerevisiae L11, and of non-probiotic strains S. cerevisiae BY4741 and S. cerevisiae BY4743. Strains 905 and Sc47 had lower and higher lipid droplet levels, respectively, when compared to the remaining strains, showing that higher accumulationof these neutral lipids is not a feature shared by all probiotic Saccharomyces strains. When submitted to simulated gastric or bile salts environments, lipid droplet levels increase in all tested probiotic strains, at least for one to the induced stresses, suggesting that lipid droplets participate in the protective mechanisms against gastrointestinal stresses in probiotic Saccharomyces yeasts

DIS-EMBODIED LANGUAGE: L'ACQUISIZIONE LINGUISTICA IN ASSENZA DI RIFERIMENTI ORO-ARTICOLATORI. L'ELOQUIO DEL BAMBINO DISPRASSICO ITALIANO.

La tesi fornisce una prima classificazione sistematica dei fenomeni fonetico-fonologici che caratterizzano l'eloquio del bambino, di lingua italiana, affetto da disprassia verbale in età evolutiva. Presenta, inoltre, un'ipotesi di lettura della patologia dal punto da un punto di vista "embodied" ed ipotesi di ricerca attinenti

Runx1+ vascular smooth muscle cells are essential for hematopoietic stem and progenitor cell development in vivo

Hematopoietic stem cells (HSCs) produce all essential cellular components of the blood. Stromal cell lines supporting HSCs follow a vascular smooth muscle cell (vSMC) differentiation pathway, suggesting that some hematopoiesis-supporting cells originate from vSMC precursors. These pericyte-like precursors were recently identified in the aorta-gonad-mesonephros (AGM) region; however, their role in the hematopoietic development in vivo remains unknown. Here, we identify a subpopulation of NG2 +Runx1 + perivascular cells that display a sclerotome-derived vSMC transcriptomic profile. We show that deleting Runx1 in NG2 + cells impairs the hematopoietic development in vivo and causes transcriptional changes in pericytes/vSMCs, endothelial cells and hematopoietic cells in the murine AGM. Importantly, this deletion leads also to a significant reduction of HSC reconstitution potential in the bone marrow in vivo. This defect is developmental, as NG2 +Runx1 + cells were not detected in the adult bone marrow, demonstrating the existence of a specialised pericyte population in the HSC-generating niche, unique to the embryo. </p

Adiponectin, leptin, and IGF-1 are useful diagnostic and stratification biomarkers of NAFLD

[EN] Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome. Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics. Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p < 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p < 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; p < 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p<0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p < 0.01). Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis.CR was funded by FEDER through the COMPETE program and by national funds through Fundação para a Ciência e a Tecnologia (PTDC/MED-FAR/29097/2017—LISBOA-01- 0145-FEDER-029097) and by European Horizon 2020 (H2020- MSCA-RISE-2016-734719). This work was also supported by Fundação para a Ciência e Tecnologia (PD/BD/135467/2017) and Portuguese Association for the Study of Liver/MSD 2017. JB was funded by Spanish Carlos III Health Institute (ISCIII) (PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 and CPII19/00008), co-financed by Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III (CIBERehd, Spain), La Caixa Scientific Foundation (HR17-00601), Fundación Científica de la Asociación Española Contra el Cáncer, and European Horizon 2020 (ESCALON project: H2020-SC1-BHC-2018-2020)

Gauged Double Field Theory

We find necessary and sufficient conditions for gauge invariance of the action of Double Field Theory (DFT) as well as closure of the algebra of gauge symmetries. The so-called weak and strong constraints are sufficient to satisfy them, but not necessary. We then analyze compactifications of DFT on twisted double tori satisfying the consistency conditions. The effective theory is a Gauged DFT where the gaugings come from the duality twists. The action, bracket, global symmetries, gauge symmetries and their closure are computed by twisting their analogs in the higher dimensional DFT. The non-Abelian heterotic string and lower dimensional gauged supergravities are particular examples of Gauged DFT.Comment: Minor changes, references adde

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes

In this large clinical series of Brazilian children and adolescents, autoimmunehepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higherdisease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.sentation, laboratory findings, histological profile, treatments, and outcomes of children andadolescents with autoimmune hepatitis.Methods: The medical records of 828 children and adolescents with autoimmune hepatitiswere reviewed. A questionnaire was used to collect anonymous data on clinical presentation,biochemical and histological findings, and treatments.Results: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmunehepatitis-2. The female sex was predominant in both groups. The median age at symptomonset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher forautoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patientswith autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-foldhigher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were sig-nificantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels werelower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochem-ical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6%underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmunehepatitis-2: 2.4%).Conclusions: In this large clinical series of Brazilian children and adolescents, autoimmunehepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higherdisease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.info:eu-repo/semantics/publishedVersio

MACROECOLOGIA, BIOGEOGRAFIA E ÁREAS PRIORITÁRIAS PARA CONSERVAÇÃO NO CERRADO

revista vol 13 nº 3.indd Há consenso entre os cientistas de que a há atualmente uma “crise da biodiversidade”, resultado da constante e intensa perda de habitat natural causada pela expansão da ocupação. Como a biologia da conservação tem sido muitas vezes reconhecida como uma ciência da crise, ela deve fornecer informações capazes de mediar, de forma mais científica possível, as tomadas de decisão que são necessárias. Dentre estas, uma das mais importantes é indicar regiões prioritárias para a conservação, já que por motivos óbvios não é possível preservar todos os ecossistemas por inteiro. Nesse contexto, recentemente sugeriu-se que a aplicação de princípios, teorias e análises provenientes da biogeografia e da macroecologia seriam importantes na Biologia da Conservação, formalizando uma abordagem que tem sido denominada “Biogeografia da Conservação”. Assim, o objetivo deste artigo é discutir e revisar esses componentes da biogeografia da conservação, utilizando uma abordagem macroecológica para desenvolver e aplicar métodos de planejamento sistemático em conservação, utilizando o bioma Cerrado como um modelo de estudo. Foram discutidos inicialmente os padrões de riqueza e diversidade beta e, em um segundo momento, como esses padrões podem ser correlacionados à ocupação humana do Bioma. Essa relação é fundamental para subsidiar a aplicação de modelos de planejamento sistemático de conservação em escala regional (análises de insubstituibilidade, complementaridade e de lacunas). É preciso considerar também que há sérias falhas de conhecimento sobre os padrões de biodiversidade na região e que a escolha de grupos indicadores pode ser importante para minimizar problemas gerados pela falta de conhecimento. Assim, essa abordagem é interessante em um cenário de grandes incertezas (ausência de dados detalhados) e de rápida transformação da paisagem, possibilitando a otimização de estudos em grandes escalas e depois transferir os resultados para escalas espaciais mais locais e realmente relevantes para a conservação. Nessas regiões, podem ser realizados, em um segundo momento, estudos mais detalhados a fim de avaliar padrões de viabilidade populacional, fragmentação de habitat e regiões potenciais de manutenção da diversidade genética