Structure of the yeast ceramide synthase.

Ceramides are essential lipids involved in forming complex sphingolipids and acting as signaling molecules. They result from the N-acylation of a sphingoid base and a CoA-activated fatty acid, a reaction catalyzed by the ceramide synthase (CerS) family of enzymes. Yet, the precise structural details and catalytic mechanisms of CerSs have remained elusive.

Complex sphingolipid profiling and identification of an inositol-phosphorylceramide synthase in .

is a professional phagocyte frequently used to study cellular processes underlying the recognition, engulfment, and infection course of microbial pathogens. Sphingolipids are abundant components of the plasma membrane that bind cholesterol, control membrane properties, participate in signal transmission, and serve as adhesion molecules in recognition processes relevant to immunity and infection. By combining lipidomics with a bioinformatics-based cloning strategy, we show here that produces phosphoinositol-containing sphingolipids with predominantly phytoceramide backbones.

The structure of the Orm2-containing serine palmitoyltransferase complex reveals distinct inhibitory potentials of yeast Orm proteins.

Sphingolipid levels are crucial determinants of neurodegenerative disorders and therefore require tight regulation. The Orm protein family and ceramides inhibit the rate-limiting step of sphingolipid biosynthesis-the condensation of L-serine and palmitoyl-coenzyme A (CoA). The yeast isoforms Orm1 and Orm2 form a complex with the serine palmitoyltransferase (SPT).

Structure of the endosomal CORVET tethering complex.

Cells depend on their endolysosomal system for nutrient uptake and downregulation of plasma membrane proteins. These processes rely on endosomal maturation, which requires multiple membrane fusion steps. Early endosome fusion is promoted by the Rab5 GTPase and its effector, the hexameric CORVET tethering complex, which is homologous to the lysosomal HOPS.

Identification of distinct active pools of yeast serine palmitoyltransferase in sub-compartments of the ER.

Sphingolipids (SPs) are one of the three major lipid classes in eukaryotic cells and serve as structural components of the plasma membrane. The rate-limiting step in SP biosynthesis is catalyzed by the serine palmitoyltransferase (SPT). In budding yeast (Saccharomyces cerevisiae), SPT is negatively regulated by the two proteins, Orm1 and Orm2.

Structure of the ceramide-bound SPOTS complex.

Sphingolipids are structural membrane components that also function in cellular stress responses. The serine palmitoyltransferase (SPT) catalyzes the rate-limiting step in sphingolipid biogenesis. Its activity is tightly regulated through multiple binding partners, including Tsc3, Orm proteins, ceramides, and the phosphatidylinositol-4-phosphate (PI4P) phosphatase Sac1.

Honey bees infer source location from the dances of returning foragers.

Honeybees () communicate the direction and distance to a food source by means of a waggle dance. We ask whether bees recruited by the dance use it only as a flying instruction, with the technical form of a polar vector, or also translate it into a location vector that enables them to set courses directed toward the food source from arbitrary locations within their familiar territory. The flights of recruits captured on exiting the hive and released at distant sites were tracked by radar.

Yeast Svf1 binds ceramides and contributes to sphingolipid metabolism at the ER cis-Golgi interface.

Ceramides are essential precursors of complex sphingolipids and act as potent signaling molecules. Ceramides are synthesized in the endoplasmic reticulum (ER) and receive their head-groups in the Golgi apparatus, yielding complex sphingolipids (SPs). Transport of ceramides between the ER and the Golgi is executed by the essential ceramide transport protein (CERT) in mammalian cells.

Seroprevalence against Toscana virus in Spain: The case of the autonomous community of Madrid.

Background & Objectives: The Toscana virus (TOSV) is a neurotropic arbovirus that is transmitted through the bite of some Phlebotomus species. In 2009, the largest outbreak of leishmaniasis described so far in Europe, occurred in the Autonomous Community of Madrid, Spain, which was related to the population increase of P. perniciosus in this region.

Neprilysins regulate muscle contraction and heart function via cleavage of SERCA-inhibitory micropeptides.

Muscle contraction depends on strictly controlled Ca transients within myocytes. A major player maintaining these transients is the sarcoplasmic/endoplasmic reticulum Ca ATPase, SERCA. Activity of SERCA is regulated by binding of micropeptides and impaired expression or function of these peptides results in cardiomyopathy.

Cvm1 is a component of multiple vacuolar contact sites required for sphingolipid homeostasis.

Membrane contact sites are specialized platforms formed between most organelles that enable them to exchange metabolites and influence the dynamics of each other. The yeast vacuole is a degradative organelle equivalent to the lysosome in higher eukaryotes with important roles in ion homeostasis and metabolism. Using a high-content microscopy screen, we identified Ymr160w (Cvm1, for contact of the vacuole membrane 1) as a novel component of three different contact sites of the vacuole: with the nuclear endoplasmic reticulum, the mitochondria, and the peroxisomes.

Differential Association of Frailty and Sarcopenia With Mortality and Disability: Insight Supporting Clinical Subtypes of Frailty.

Objectives: Sarcopenia and frailty have been shown separately to predict disability and death in old age. Our aim was to determine if sarcopenia may modify the prognosis of frailty regarding both mortality and disability, raising the existence of clinical subtypes of frailty depending on the presence of sarcopenia.

Design: A Spanish longitudinal population-based study.

Burden of respiratory syncytial virus-associated lower respiratory infections in children in Spain from 2012 to 2018.

Background: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection (ALRI) leading to infant hospitalization, morbidity and postnatal mortality in children younger than 5 years of age worldwide. The aim of this study was to collect data on hospitalizations for RSV-related ALRI in children in Spain from 2012 to 2018.

Methods: We used the discharge reports from the Minimum Basic Data Set (MBDS) to retrospectively analyze hospital discharge data in children ≤ 14 years of age with a diagnosis of acute lower respiratory tract infection, based on the ICD-9-CM and ICD-10-CM diagnosis codes, from 2012 to 2018.

The yeast LYST homolog Bph1 is a Rab5 effector and prevents Atg8 lipidation at endosomes.

Lysosomes mediate degradation of macromolecules to their precursors for cellular recycling. Additionally, lysosome-related organelles mediate cell type-specific functions. Chédiak-Higashi syndrome is an autosomal, recessive disease, in which loss of the protein LYST causes defects in lysosomes and lysosome-related organelles.

A lysosomal biogenesis map reveals the cargo spectrum of yeast vacuolar protein targeting pathways.

The lysosome is the major catabolic organelle in the cell that has been established as a key metabolic signaling center. Mutations in many lysosomal proteins have catastrophic effects and cause neurodegeneration, cancer, and age-related diseases. The vacuole is the lysosomal analog of Saccharomyces cerevisiae that harbors many evolutionary conserved proteins.

Low membrane fluidity triggers lipid phase separation and protein segregation in living bacteria.

All living organisms adapt their membrane lipid composition in response to changes in their environment or diet. These conserved membrane-adaptive processes have been studied extensively. However, key concepts of membrane biology linked to regulation of lipid composition including homeoviscous adaptation maintaining stable levels of membrane fluidity, and gel-fluid phase separation resulting in domain formation, heavily rely upon in vitro studies with model membranes or lipid extracts.

Impact of Penicillin Allergy Label on Length of Stay and Mortality in Hospitalized Patients through a Clinical Administrative National Dataset.

Background: Penicillin allergy is a common problem in the management of infectious diseases. The aim of this study was to determine the impact of penicillin allergy on length of hospital stay (LOHS) among hospitalized adult patients and on in-hospital mortality at a national level.

Methods: A retrospective cohort study of adult patients discharged from the Spanish Hospital System between 2006 and 2015 was conducted using the Minimum Basic Data Set (MBDS).

Hospitalizations related to meningococcal infection in Spain from 1997 to 2018.

Background: Baseline hospitalization, mortality, and in-hospital fatality rates for meningococcal infection are required to evaluate preventive interventions, such as the inclusion of the conjugated quadrivalent meningococcal vaccine and serogroup B based protein vaccines.

Methods: All meningococcal infection-related hospitalizations in any diagnostic position in Spain from 1st January 1997 through 31st December 2018 were analysed. The annual hospitalization rate, mortality rate and case-fatality rate were calculated.

Prognostic factors and combined use of tocilizumab and corticosteroids in a Spanish cohort of elderly COVID-19 patients.

Coronavirus disease 2019 (COVID-19) infection in elderly patients is more aggressive and treatments have shown limited efficacy. Our objective is to describe the clinical course and to analyze the prognostic factors associated with a higher risk of mortality of a cohort of patients older than 80 years. In addition, we assess the efficacy of immunosuppressive treatments in this population.

Explaining the Variance in Cardiovascular Disease Risk Factors: A Comparison of Demographic, Socioeconomic, and Genetic Predictors.

Background: Efforts to explain the burden of cardiovascular disease (CVD) often focus on genetic factors or social determinants of health. There is little evidence on the comparative predictive value of each, which could guide clinical and public health investments in measuring genetic versus social information. We compared the variance in CVD-related outcomes explained by genetic versus socioeconomic predictors.

Subunit exchange among endolysosomal tethering complexes is linked to contact site formation at the vacuole.

The hexameric HOPS (homotypic fusion and protein sorting) complex is a conserved tethering complex at the lysosome-like vacuole, where it mediates tethering and promotes all fusion events involving this organelle. The Vps39 subunit of this complex also engages in a membrane contact site between the vacuole and the mitochondria, called vCLAMP. Additionally, four subunits of HOPS are also part of the endosomal CORVET tethering complex.

Burden of pneumonia in patients with viral and bacterial coinfection in Spain during six consecutive influenza seasons, from 2009-10 to 2014-15.

Purpose: Lower respiratory infections remain the most lethal communicable disease worldwide. Viral and bacterial coinfections (VBC) are common complications in patients with seasonal influenza and are associated with around 25% of all influenza-related deaths. The burden of pneumonia in patients with VBC in Spain is poorly characterized.

Dose accuracy improvement on head and neck VMAT treatments by using the Acuros algorithm and accurate FFF beam calibration.

Background: The purpose of this study was to assess dose accuracy improvement and dosimetric impact of switching from the anisotropic analytical algorithm (AA) to the Acuros XB algorithm (AXB) when performing an accurate beam calibration in head and neck (H&N) FFF-VMAT treatments.

Materials And Methods: Twenty H&N cancer patients treated with FFF-VMAT techniques were included. Calculations were performed with the AA and AXB algorithm (dose-to-water - AXB- and dose-to-medium - AXB-).