Notes

Household lifestyle compared to institutional medical center tradition: a relationship between a pair of planets.
The present results may open up a new strategy to realize new lead-free piezoelectric materials.The exchange of metabolites between environment and coral tissue depends on the flux across the diffusive boundary layer (DBL) surrounding the tissue. Cilia covering the coral tissue have been shown to create vortices that enhance mixing in the DBL in stagnant water. To study the role of cilia under simulated ambient currents, we designed a new light-sheet microscopy based flow chamber setup. Microparticle velocimetry was combined with high-resolution oxygen profiling in the coral Porites lutea under varying current and light conditions with natural and arrested cilia beating. Cilia-generated vortices in the lower DBL mitigated extreme oxygen concentrations close to the tissue surface. Under light and arrested cilia, oxygen surplus at the tissue surface increased to 350 µM above ambient, in contrast to 25 µM under ciliary beating. Oxygen shortage in darkness decreased from 120 µM (cilia arrested) to 86 µM (cilia active) below ambient. Ciliary redistribution of oxygen had no effect on the photosynthetic efficiency of the photosymbionts and overall oxygen flux across the DBL indicating that oxygen production and consumption was not affected. We found that corals actively change their environment and suggest that ciliary flows serve predominantly as a homeostatic control mechanism which may play a crucial role in coral stress response and resilience.An amendment to this paper has been published and can be accessed via a link at the top of the paper.The durum wheat line DT696 is a source of moderate Fusarium head blight (FHB) resistance. Previous analysis using a bi-parental population identified two FHB resistance quantitative trait loci (QTL) on chromosome 5A 5A1 was co-located with a plant height QTL, and 5A2 with a major maturity QTL. A Genome-Wide Association Study (GWAS) of DT696 derivative lines from 72 crosses based on multi-environment FHB resistance, plant height, and maturity phenotypic data was conducted to improve the mapping resolution and further elucidate the genetic relationship of height and maturity with FHB resistance. The Global Tetraploid Wheat Collection (GTWC) was exploited to identify durum wheat lines with DT696 allele and additional recombination events. The 5A2 QTL was confirmed in the derivatives, suggesting the expression stability of the 5A2 QTL in various genetic backgrounds. The GWAS led to an improved mapping resolution rendering the 5A2 interval 10 Mbp shorter than the bi-parental QTL mapping interval. Haplotype analysis using SNPs within the 5A2 QTL applied to the GTWC identified novel haplotypes and recombination breakpoints, which could be exploited for further improvement of the mapping resolution. This study suggested that GWAS of derivative breeding lines is a credible strategy for improving mapping resolution.The limited number of antifungals and the rising frequency of azole-resistant Candida species are growing challenges to human medicine. Drug repurposing signifies an appealing approach to enhance the activity of current antifungal drugs. Here, we evaluated the ability of Pharmakon 1600 drug library to sensitize an azole-resistant Candida albicans to the effect of fluconazole. The primary screen revealed 44 non-antifungal hits were able to act synergistically with fluconazole against the test strain. Of note, 21 compounds, showed aptness for systemic administration and limited toxic effects, were considered as potential fluconazole adjuvants and thus were termed as "repositionable hits". A follow-up analysis revealed pitavastatin displaying the most potent fluconazole chemosensitizing activity against the test strain (ΣFICI 0.05) and thus was further evaluated against 18 isolates of C. albicans (n = 9), C. glabrata (n = 4), and C. auris (n = 5). Pitavastatin displayed broad-spectrum synergistic interactions with both fluconazole and voriconazole against ~89% of the tested strains (ΣFICI 0.05-0.5). CID-1067700 ic50 Additionally, the pitavastatin-fluconazole combination significantly reduced the biofilm-forming abilities of the tested Candida species by up to 73%, and successfully reduced the fungal burdens in a Caenorhabditis elegans infection model by up to 96%. This study presents pitavastatin as a potent azole chemosensitizing agent that warrant further investigation.Delivery of drugs into the brain is poor due to the blood brain barrier (BBB). This study describes the development of a novel liposome-based brain-targeting drug delivery system. The liposomes incorporate a diacylglycerol moiety coupled through a linker to a peptide of 5 amino acids selected from amyloid precursor protein (APP), which is recognized by specific transporter(s)/receptor(s) in the BBB. This liposomal system enables the delivery of drugs across the BBB into the brain. The brain-directed liposomal system was used in a mouse model of Parkinson's disease (PD). Intra-peritoneal (IP) administration of liposomes loaded with dopamine (DA) demonstrated a good correlation between liposomal DA dose and the behavioral effects in hemiparkinsonian amphetamine-treated mice, with an optimal DA dose of 60 µg/kg. This is significantly lower dose than commonly used doses of the DA precursor levodopa (in the mg/kg range). IP injection of the APP-targeted liposomes loaded with a DA dose of 800 µg/kg, resulted in a significant increase in striatal DA within 5 min (6.9-fold, p  less then  0.05), in amphetamine-treated mice. The increase in striatal DA content persisted for at least 3 h after administration, which indicates a slow DA release from the delivery system. No elevation in DA content was detected in the heart or the liver. Similar increases in striatal DA were observed also in rats and mini-pigs. The liposomal delivery system enables penetration of compounds through the BBB and may be a candidate for the treatment of PD and other brain diseases.Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P  less then  5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.Psychiatry is undergoing a paradigm shift from the acceptance of distinct diagnoses to a representation of psychiatric illness that crosses diagnostic boundaries. How this transition is supported by a shared neurobiology remains largely unknown. In this study, we first identify single nucleotide polymorphisms (SNPs) associated with psychiatric disorders based on 136 genome-wide association studies. We then conduct a joint analysis of these SNPs and brain structural connectomes in 678 healthy children in the PING study. We discovered a strong, robust, and transdiagnostic mode of genome-connectome covariation which is positively and specifically correlated with genetic risk for psychiatric illness at the level of individual SNPs. Similarly, this mode is also significantly positively correlated with polygenic risk scores for schizophrenia, alcohol use disorder, major depressive disorder, a combined bipolar disorder-schizophrenia phenotype, and a broader cross-disorder phenotype, and significantly negatively correlated with a polygenic risk score for educational attainment. The resulting "vulnerability network" is shown to mediate the influence of genetic risks onto behaviors related to psychiatric vulnerability (e.g., marijuana, alcohol, and caffeine misuse, perceived stress, and impulsive behavior). Its anatomy overlaps with the default-mode network, with a network of cognitive control, and with the occipital cortex. These findings suggest that the brain vulnerability network represents an endophenotype funneling genetic risks for various psychiatric illnesses through a common neurobiological root. It may form part of the neural underpinning of the well-recognized but poorly explained overlap and comorbidity between psychiatric disorders.Ammonia is one of the most basic components on the planet and its high-pressure characteristics play an important role in planetary science. Solid ammonia crystals frequently adopt multiple distinct polymorphs exhibiting different properties. Predicting the crystal structure of these polymorphs and under what thermodynamic conditions these polymorphs are stable would be of great value to environmental industry and other fields. Theoretical calculations based on the classical force fields and density-functional theory (DFT) are versatile methods but lack of accurate description of weak intermolecular interactions for molecular crystals. In this study, we employ an ab initio computational study on the solid ammonia at high pressures, using the second-order Møller-Plesset perturbation (MP2) theory and the coupled cluster singles, doubles, and perturbative triples (CCSD(T)) theory along with the embedded fragmentation method. The proposed algorithm is capable of performing large-scale calculations using high-level wavefunction theories, and accurately describing covalent, ionic, hydrogen bonding, and dispersion interactions within molecular crystals, and therefore can predict the crystal structures, Raman spectra and phase transition of solid ammonia phases I and IV accurately. We confirm the crystal structures of solid ammonia phases I and IV that have been controversial for a long time and predict their phase transition that occurs at 1.17 GPa and 210 K with small temperature dependence, which is in line with experiment.Plant growth promoting rhizobacteria can improve plant health by providing enhanced nutrition, disease suppression and abiotic stress resistance, and have potential to contribute to sustainable agriculture. We have developed a sphagnum peat-based compost platform for investigating plant-microbe interactions. The chemical, physical and biological status of the system can be manipulated to understand the relative importance of these factors for plant health, demonstrated using three case studies 1. Nutrient depleted compost retained its structure, but plants grown in this medium were severely stunted in growth due to removal of essential soluble nutrients - particularly, nitrogen, phosphorus and potassium. Compost nutrient status was replenished with the addition of selected soluble nutrients, validated by plant biomass; 2. When comparing milled and unmilled compost, we found nutrient status to be more important than matrix structure for plant growth; 3. In compost deficient in soluble P, supplemented with an insoluble inorganic form of P (Ca3(PO4)2), application of a phosphate solubilising Pseudomonas strain to plant roots provides a significant growth boost when compared with a Pseudomonas strain incapable of solubilising Ca3(PO4)2.
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