Solvable Lie algebras are not that hypo

We study a type of left-invariant structure on Lie groups, or equivalently on Lie algebras. We introduce obstructions to the existence of a hypo structure, namely the 5-dimensional geometry of hypersurfaces in manifolds with holonomy SU(3). The choice of a splitting g^*=V_1 + V_2, and the vanishing of certain associated cohomology groups, determine a first obstruction. We also construct necessary conditions for the existence of a hypo structure with a fixed almost-contact form. For non-unimodular Lie algebras, we derive an obstruction to the existence of a hypo structure, with no choice involved. We apply these methods to classify solvable Lie algebras that admit a hypo structure.Comment: 21 pages; v2: presentation improved, typos corrected, notational conflicts eliminated. To appear in Transformation Group

Enzymatic Solid-Phase Reactor Based on Silica Organofunctionalized with p-Phenylenediamine for Electrochemical Detection of Phenolic Compounds

A new biomaterial, based on silica organofunctionalized with p-phenylenediamine (p-PDA) and the enzyme peroxidase, was used in the development of an enzymatic solid-phase reactor. The analytical techniques used in the characterization showed that the organic ligand was incorporated into the silica matrix. Thus, the silica modified with p-PDA allowed the incorporation of peroxidase by the electrostatic interaction between the carboxylic groups present in the enzyme molecules and the amino groups attached to the silica. The enzymatic solid-phase reactor was used for chemical oxidation of phenols in 1 4-benzoquinone that was then detected by chronoamperometry. The system allowed the analysis of hydroquinone with a detection limit of 83.6 nmol L −1 . Thus, the new material has potential in the determination of phenolic compounds river water samples

Cardiovascular and renal outcomes of renin-angiotensin system blockade in adult patients with diabetes mellitus: a systematic review with network meta-analyses

Medications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes

Incense smoke: clinical, structural and molecular effects on airway disease

In Asian countries where the Buddhism and Taoism are mainstream religions, incense burning is a daily practice. A typical composition of stick incense consists of 21% (by weight) of herbal and wood powder, 35% of fragrance material, 11% of adhesive powder, and 33% of bamboo stick. Incense smoke (fumes) contains particulate matter (PM), gas products and many organic compounds. On average, incense burning produces particulates greater than 45 mg/g burned as compared to 10 mg/g burned for cigarettes. The gas products from burning incense include CO, CO2, NO2, SO2, and others. Incense burning also produces volatile organic compounds, such as benzene, toluene, and xylenes, as well as aldehydes and polycyclic aromatic hydrocarbons (PAHs). The air pollution in and around various temples has been documented to have harmful effects on health. When incense smoke pollutants are inhaled, they cause respiratory system dysfunction. Incense smoke is a risk factor for elevated cord blood IgE levels and has been indicated to cause allergic contact dermatitis. Incense smoke also has been associated with neoplasm and extracts of particulate matter from incense smoke are found to be mutagenic in the Ames Salmonella test with TA98 and activation. In order to prevent airway disease and other health problem, it is advisable that people should reduce the exposure time when they worship at the temple with heavy incense smokes, and ventilate their house when they burn incense at home

Calcineurin Inhibition at the Clinical Phase of Prion Disease Reduces Neurodegeneration, Improves Behavioral Alterations and Increases Animal Survival

Prion diseases are fatal neurodegenerative disorders characterized by a long pre-symptomatic phase followed by rapid and progressive clinical phase. Although rare in humans, the unconventional infectious nature of the disease raises the potential for an epidemic. Unfortunately, no treatment is currently available. The hallmark event in prion diseases is the accumulation of a misfolded and infectious form of the prion protein (PrPSc). Previous reports have shown that PrPSc induces endoplasmic reticulum stress and changes in calcium homeostasis in the brain of affected individuals. In this study we show that the calcium-dependent phosphatase Calcineurin (CaN) is hyperactivated both in vitro and in vivo as a result of PrPSc formation. CaN activation mediates prion-induced neurodegeneration, suggesting that inhibition of this phosphatase could be a target for therapy. To test this hypothesis, prion infected wild type mice were treated intra-peritoneally with the CaN inhibitor FK506 at the clinical phase of the disease. Treated animals exhibited reduced severity of the clinical abnormalities and increased survival time compared to vehicle treated controls. Treatment also led to a significant increase in the brain levels of the CaN downstream targets pCREB and pBAD, which paralleled the decrease of CaN activity. Importantly, we observed a lower degree of neurodegeneration in animals treated with the drug as revealed by a higher number of neurons and a lower quantity of degenerating nerve cells. These changes were not dependent on PrPSc formation, since the protein accumulated in the brain to the same levels as in the untreated mice. Our findings contribute to an understanding of the mechanism of neurodegeneration in prion diseases and more importantly may provide a novel strategy for therapy that is beneficial at the clinical phase of the disease

Progesterone from the Cumulus Cells Is the Sperm Chemoattractant Secreted by the Rabbit Oocyte Cumulus Complex

Sperm chemotaxis in mammals have been identified towards several female sources as follicular fluid (FF), oviduct fluid, and conditioned medium from the cumulus oophorus (CU) and the oocyte (O). Though several substances were confirmed as sperm chemoattractant, Progesterone (P) seems to be the best chemoattractant candidate, because: 1) spermatozoa express a cell surface P receptor, 2) capacitated spermatozoa are chemotactically attracted in vitro by gradients of low quantities of P; 3) the CU cells produce and secrete P after ovulation; 4) a gradient of P may be kept stable along the CU; and 5) the most probable site for sperm chemotaxis in vivo could be near and/or inside the CU. The aim of this study was to verify whether P is the sperm chemoattractant secreted by the rabbit oocyte-cumulus complex (OCC) in the rabbit, as a mammalian animal model. By means of videomicroscopy and computer image analysis we observed that only the CU are a stable source of sperm attractants. The CU produce and secrete P since the hormone was localized inside these cells by immunocytochemistry and in the conditioned medium by enzyme immunoassay. In addition, rabbit spermatozoa express a cell surface P receptor detected by western blot and localized over the acrosomal region by immunocytochemistry. To confirm that P is the sperm chemoattractant secreted by the CU, the sperm chemotactic response towards the OCC conditioned medium was inhibited by three different approaches: P from the OCC conditioned medium was removed with an anti-P antibody, the attractant gradient of the OCC conditioned medium was disrupted by a P counter gradient, and the sperm P receptor was blocked with a specific antibody. We concluded that only the CU but not the oocyte secretes P, and the latter chemoattract spermatozoa by means of a cell surface receptor. Our findings may be of interest in assisted reproduction procedures in humans, animals of economic importance and endangered species

Factors driving extensive spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals

The SARS‐CoV‐2 Gamma variant spread rapidly across Brazil, causing substantial infection and death wa ves. We use individual‐level patient records following hospitalisation with suspected or confirmed COVID‐19 to document the extensive shocks in hospital fatality rates that followed Gamma’s spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time pe riods. We show that extensive fluctuations in COVID‐19 in‐hospital fatality rates also existed prior to Gamma’s detection, and were largely transient after Gamma’s detection, subsiding with hospital d emand. Using a Bayesian fatality rate model, we find that the geo‐graphic and temporal fluctuations in Brazil’s COVID‐19 in‐hospital fatality rates are primarily associated with geo‐graphic inequities and shortages in healthcare c apacity. We project that approximately half of Brazil’s COVID‐19 deaths in hospitals could have been avoided without pre‐pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly trans‐missible and deadly pathogens such as SARS‐CoV‐2, especially in low‐ and middle‐income countries

Increased Expression of Fatty-Acid and Calcium Metabolism Genes in Failing Human Heart

Heart failure (HF) involves alterations in metabolism, but little is known about cardiomyopathy-(CM)-specific or diabetes-independent alterations in gene expression of proteins involved in fatty-acid (FA) uptake and oxidation or in calcium-(Ca(2+))-handling in the human heart.RT-qPCR was used to quantify mRNA expression and immunoblotting to confirm protein expression in left-ventricular myocardium from patients with HF (n = 36) without diabetes mellitus of ischaemic (ICM, n = 16) or dilated (DCM, n = 20) cardiomyopathy aetiology, and non-diseased donors (CTL, n = 6).Significant increases in mRNA of genes regulating FA uptake (CD36) and intracellular transport (Heart-FA-Binding Protein (HFABP)) were observed in HF patients vs CTL. Significance was maintained in DCM and confirmed at protein level, but not in ICM. mRNA was higher in DCM than ICM for peroxisome-proliferator-activated-receptor-alpha (PPARA), PPAR-gamma coactivator-1-alpha (PGC1A) and CD36, and confirmed at the protein level for PPARA and CD36. Transcript and protein expression of Ca(2+)-handling genes (Two-Pore-Channel 1 (TPCN1), Two-Pore-Channel 2 (TPCN2), and Inositol 1,4,5-triphosphate Receptor type-1 (IP3R1)) increased in HF patients relative to CTL. Increases remained significant for TPCN2 in all groups but for TPCN1 only in DCM. There were correlations between FA metabolism and Ca(2+)-handling genes expression. In ICM there were six correlations, all distinct from those found in CTL. In DCM there were also six (all also different from those found in CTL): three were common to and three distinct from ICM.DCM-specific increases were found in expression of several genes that regulate FA metabolism, which might help in the design of aetiology-specific metabolic therapies in HF. Ca(2+)-handling genes TPCN1 and TPCN2 also showed increased expression in HF, while HF- and CM-specific positive correlations were found among several FA and Ca(2+)-handling genes

Refractory dispersion promotes conduction disturbance and arrhythmias in a Scn5a+/− mouse model

Accentuated right ventricular (RV) gradients in action potential duration (APD) have been implicated in the arrhythmogenicity observed in Brugada syndrome in studies assuming that ventricular effective refractory periods (VERPs) vary in concert with APDs. The present experiments use a genetically modified mouse model to explore spatial heterogeneities in VERP that in turn might affect conduction velocity, thereby causing arrhythmias. Activation latencies, APDs and VERPs recorded during programmed S1S2 protocols were compared in RV and left ventricular (LV) epicardia and endocardia of Langendorff-perfused wild-type (WT) and Scn5a+/− hearts. Scn5a+/− and WT hearts showed similar patterns of shorter VERPs in RV than LV epicardia, and in epicardia than endocardia. However, Scn5a+/− hearts showed longer VERPs, despite shorter APD90s, than WT in all regions examined. The pro- and anti-arrhythmic agents flecainide and quinidine increased regional VERPs despite respectively decreasing and increasing the corresponding APD90s particularly in Scn5a+/− RV epicardia. In contrast, Scn5a+/− hearts showed greater VERP gradients between neighbouring regions, particularly RV transmural gradients, than WT (9.1 ± 1.1 vs. 5.7 ± 0.5 ms, p < 0.05, n = 12). Flecainide increased (to 21 ± 0.9 ms, p < 0.05, n = 6) but quinidine decreased (to 4.5 ± 0.5 ms, p < 0.05, n = 6) these gradients, particularly across the Scn5a+/− RV. Finally, Scn5a+/− hearts showed greater conduction slowing than WT following S2 stimuli, particularly with flecainide administration. Rather than arrhythmogenesis resulting from increased transmural repolarization gradients in an early, phase 2, reentrant excitation mechanism, the present findings implicate RV VERP gradients in potential reentrant mechanisms involving impulse conduction slowed by partial refractoriness