1914G variant of BCHE gene associated with enzyme activity,obesity and triglyceride levels

Polymorphisms of butyrylcholinesterase (BChE) have been reported to be associated to weight, BMI variance and hypertriglyceridemia in adults and adolescents. The aim of the present study was to investigate the association of −116A (SNP: G/A; rs1126680) and 1914G (SNP: A/G; rs3495) variants of BCHE gene with anthropometric and biochemical variables associated with obesity in population sample of 115 individuals, from Southern Brazil. Participants were grouped in two categories: obese (BMI ≥ 30) and non-obese (BMI < 30). The 1914G allele showed significantly higher frequency in the obese group, and carriers of 1914G allele showed lower mean BChE activity when compared to 1914A carriers (p = 0.006). Higher means of BMI (p = 0.02) and triglyceride (TG; p = 0.01) were found in 1914G carriers (BMI = 27.57kg/m²; TG = 150.8 mg/dL) when compared to 1914A homozygotes (BMI = 25.55 kg/m²; TG = 107.9 mg/dL). Carriers of the −116A allele showed lower mean BChE activity than usual homozygotes, and the −116A variant was found in cis with 1914G (p < 0.0001; D′ = 1). The region of BCHE gene that contains the 1914G mutation site is target of microRNAs (miRs) and the response of BChE to glucocorticoids is especially influenced by these miRs. Therefore, it is possible that the 1914G allele can be interfering in gluconeogenesis, hyperglycemia, lipolysis and body fat distribution. This lower activity may cause an imbalance in lipid metabolism, which may lead to an increased predisposition to obesity and to a lower ability to maintain metabolic homeostasis.     

Impact of unilateral spatial neglect on chronic patient's post-stroke quality of life

Abstract

Background: Unilateral spatial neglect (USN) is the prevalent feature in patients with right-sided stroke. It is diagnosed through the behavior inattention test (BIT) and has a negative impact on patients affecting both their functional capacity and quality of life.

Objective: Here, we aimed to evaluate the impact of USN on the quality of life of patients in the chronic phase of stroke.

Methods: This is a cross-sectional study with stroke patients with USN. After confirming the presence of stroke through neuroimaging examinations and of USN through the BIT, patients’ quality of life was evaluated by using the EUROQOL scale. Spearman’s correlation was used to validate the correlation between patients’ USN and quality of life, with a p?<?.05 representing significant results.

Results: Eighteen individuals were included. When correlating the value of each domain of the EUROQOL scale with the results of the BIT, we observed a negative correlation between mobility (r?=?–0.97; p?=?.000), self-care (r?=?–0.82; p?=?.013), usual activities (r?=?–0.87; p?=?.005); pain or discomfort (r?=?–0.88; p?=?.004), anxiety or depression (r?=?–0.97; p?=?.000), and EUROQOL total score (r?=?–0.97, p?=?.000).

Conclusion: After a correlation between the overall EUROQOL and BIT scores, we suggest that the higher the USN degree is in stroke patients, the worse their perceived quality of life tends to be.     

Nutrient partitioning and grain yield of TaNAM-RNAi wheat under abiotic stress

Aims

Decreased expression of TaNAM genes by RNAi results in delayed senescence and decreased grain protein, iron, and zinc concentrations. Here, we determined whether NAM expression level alters onset of senescence under stress conditions, whether delayed senescence in the TaNAM-RNAi line resulted in improved tolerance to post-anthesis abiotic stress, and determined the effects of post-anthesis abiotic stress on N and mineral remobilization and partitioning to grain.

Methods

Greenhouse-grown WT and TaNAM-RNAi wheat were characterized in two studies:three levels of N fertility or water limitation during grain fill. Studies were conducted under both optimal and heat stress temperatures. Senescence onset was determined by monitoring flag leaf chlorophyll.

Results

Under optimal tempertures, TaNAM-RNAi plants had a yield advantage at lower N. TaNAM-RNAi plants had delayed senescence relative to the WT and lower grain protein and mineral concentrations, N remobilization efficiency, and partitioning of N and most minerals to grain.

Conclusions

Nutritional quality of TaNAM-RNAi grain was consistently lower than WT. Delayed senescence of TaNAM-RNAi plants provided a yield advantage under optimal temperatures but not under water or heat stress. Discovery of specific NAM protein targets may allow separation of the delayed senescence and nutrient partitioning traits, which could be used for improvement of wheat.     

Redox-sensitive stimulation of type-1 ryanodine receptors by the scorpion toxin maurocalcine

The scorpion toxin maurocalcine acts as a high affinity agonist of the type-1 ryanodine receptor expressed in skeletal muscle. Here, we investigated the effects of the reducing agent dithiothreitol or the oxidizing reagent thimerosal on type-1 ryanodine receptor stimulation by maurocalcine. Maurocalcine addition to sarcoplasmic reticulum vesicles actively loaded with calcium elicited Ca²⁺ release from native vesicles and from vesicles pre-incubated with dithiothreitol; thimerosal addition to native vesicles after Ca²⁺ uptake completion prevented this response. Maurocalcine enhanced equilibrium [³H]-ryanodine binding to native and to dithiothreitol-treated reticulum vesicles, and increased 5-fold the apparent K_i for Mg²⁺ inhibition of [³H]-ryanodine binding to native vesicles. Single calcium release channels incorporated in planar lipid bilayers displayed a long-lived open sub-conductance state after maurocalcine addition. The fractional time spent in this sub-conductance state decreased when lowering cytoplasmic [Ca²⁺] from 10 μM to 0.1 μM or at cytoplasmic [Mg²⁺] ≥ 30 μM. At 0.1 μM [Ca²⁺], only channels that displayed poor activation by Ca²⁺ were readily activated by 5 nM maurocalcine; subsequent incubation with thimerosal abolished the sub-conductance state induced by maurocalcine. We interpret these results as an indication that maurocalcine acts as a more effective type-1 ryanodine receptor channel agonist under reducing conditions.     

Fossilization of Acidophilic Microorganisms

This study examines fossil microorganisms found in iron-rich deposits in an extreme acidic environment, the Tinto River in SW Spain. Both electron microscopy (SEM and TEM) and non-destructive in situ microanalytical techniques (EDS, EMP and XPS) were used to determine the role of permineralization and encrustation in preserving microorganisms forming biofilms in the sediments. Unicellular algae were preserved by silica permineralization of their cell walls. Bacterial biofilms were preserved as molds by epicellular deposition of schwertmannite around them. In the case of fungi and filamentous algae, we observed permineralization of cell structures by schwertmannite in the sediments. The extracellular polymeric matrix around the cells was also preserved through permineralization of the fibrillar component. The process of permineralization and deposition of iron-rich precipitates present in the acidic waters of Rio Tinto served to preserve many microfossils in an oxidizing environment, in which organic compounds would not normally be expected to persist. Studies of microbial fossil formation mechanisms in modern extreme environments should focus on defining criteria to identify inorganic traces of microbial life in past environments on Earth or other planets.     

Alteration of Tropomyosin-binding Properties of Tropomodulin-1 Affects Its Capping Ability and Localization in Skeletal Myocytes

Tropomodulin (Tmod) is an actin-capping protein that binds to the two tropomyosins (TM) at the pointed end of the actin filament to prevent further actin polymerization and depolymerization. Therefore, understanding the role of Tmod is very important when studying actin filament dependent processes such as muscle contraction and intracellular transport. The capping ability of Tmod is highly influenced by TM and is 1000-fold greater in the presence of TM. There are four Tmod isoforms (Tmod1–4), three of which, Tmod1, Tmod3, and Tmod4, are expressed in skeletal muscles. The affinity of Tmod1 to skeletal striated TM (stTM) is higher than that of Tmod3 and Tmod4 to stTM. In this study, we tested mutations in the TM-binding sites of Tmod1, using circular dichroism (CD) and prediction analysis (PONDR). The mutations R11K, D12N, and Q144K were chosen because they decreased the affinity of Tmod1 to stTM, making it similar to that of affinity of Tmod3 and Tmod4 to stTM. Significant reduction of inhibition of actin pointed-end polymerization in the presence of stTM was shown for Tmod1 (R11K/D12N/Q144K) as compared with WT Tmod1. When GFP-Tmod1 and mutants were expressed in primary chicken skeletal myocytes, decreased assembly of Tmod1 mutants was revealed. This indicates a direct correlation between TM-binding and the actin-capping abilities of Tmod. Our data confirmed the hypothesis that assembly of Tmod at the pointed-end of the actin filament depends on its TM-binding affinity.     

Unsaturated Long Chain Free Fatty Acids Are Input Signals of the Salmonella enterica PhoP/PhoQ Regulatory System

The Salmonella enterica serovar Typhimurium PhoP/PhoQ system has largely been studied as a paradigmatic two-component regulatory system not only to dissect structural and functional aspects of signal transduction in bacteria but also to gain knowledge about the versatile devices that have evolved allowing a pathogenic bacterium to adjust to or counteract environmental stressful conditions along its life cycle. Mg²⁺ limitation, acidic pH, and the presence of cationic antimicrobial peptides have been identified as cues that the sensor protein PhoQ can monitor to reprogram Salmonella gene expression to cope with extra- or intracellular challenging conditions. In this work, we show for the first time that long chain unsaturated free fatty acids (LCUFAs) present in Salmonella growth medium are signals specifically detected by PhoQ. We demonstrate that LCUFAs inhibit PhoQ autokinase activity, turning off the expression of the PhoP-dependent regulon. We also show that LCUFAs exert their action independently of their cellular uptake and metabolic utilization by means of the β-oxidative pathway. Our findings put forth the complexity of input signals that can converge to finely tune the activity of the PhoP/PhoQ system. In addition, they provide a new potential biochemical platform for the development of antibacterial strategies to fight against Salmonella infections.     

On the limitations of standard statistical modeling in biological systems: A full Bayesian approach for biology

One of the most important scientific challenges today is the quantitative and predictive understanding of biological function. Classical mathematical and computational approaches have been enormously successful in modeling inert matter, but they may be inadequate to address inherent features of biological systems. We address the conceptual and methodological obstacles that lie in the inverse problem in biological systems modeling. We introduce a full Bayesian approach (FBA), a theoretical framework to study biological function, in which probability distributions are conditional on biophysical information that physically resides in the biological system that is studied by the scientist.