Archerhoyle2184

Squalene is a triterpene hydrocarbon, a biochemical precursor for all steroids in plants and animals. It is a principal component of human surface lipids, in particular of sebum. Squalene has several applications in the food, pharmaceutical, and medical sectors. It is essentially used as a dietary supplement, vaccine adjuvant, moisturizer, cardio-protective agent, anti-tumor agent and natural antioxidant. With the increased demand for squalene along with regulations on shark-derived squalene, there is a need to find alternatives for squalene production which are low-cost as well as sustainable. Microbial platforms are being considered as a potential option to meet such challenges. Considerable progress has been made using both wild-type and engineered microbial strains for improved productivity and yields of squalene. Native strains for squalene production are usually limited by low growth rates and lesser titers. Metabolic engineering, which is a rational strain engineering tool, has enabled the development of microbial strains such as Saccharomyces cerevisiae and Yarrowia lipolytica, to overproduce the squalene in high titers. This review focuses on key strain engineering strategies involving both in-silico and in-vitro techniques. Emphasis is made on gene manipulations for improved precursor pool, enzyme modifications, cofactor regeneration, up-regulation of limiting reactions, and downregulation of competing reactions during squalene production. Process strategies and challenges related to both upstream and downstream during mass cultivation are detailed.Current treatments for dysphagia in ALS do not target the underlying tongue weakness and denervation atrophy that is prevalent in spinal and bulbar ALS cases. To address this clinical gap, we studied the low copy number SOD1-G93A (LCN-SOD1) mouse model of ALS to quantify the impact of limb phenotype on tongue denervation atrophy, dysphagia penetrance, and survival time in preparation for future treatment-based studies. Two male LCN-SOD1 breeders and 125 offspring were followed for limb phenotype inheritance, of which 52 (30 LCN-SOD1 and 22 wild-type/WT, both sexes) underwent characterization of dysphagia penetrance (via videofluoroscopic swallow study; VFSS) and survival time at disease end-stage (15-20% body weight loss). From these, 16 mice (8/genotype) underwent postmortem histological analysis of the genioglossus for evidence of denervation atrophy. Results revealed that both breeders displayed a mixed (hindlimb and forelimb) ALS phenotype and sired equal proportions of hindlimb vs. mixed phenotype offspring. Dysphagia penetrance was complete for mixed (100%) versus incomplete for hindlimb (64%) phenotype mice; yet survival times were similar. selleck chemicals llc Regardless of limb phenotype, LCN-SOD1 mice had significantly smaller genioglossus myofibers and more centralized myonuclei compared to WT mice (p  less then  0.05). These biomarkers of denervation atrophy were significantly correlated with VFSS metrics (lick and swallow rates, p  less then  0.05) but not survival time. In conclusion, both LCN-SOD1 phenotypes had significant tongue denervation atrophy, even hindlimb phenotype mice without dysphagia. This finding recapitulates human ALS, providing robust rationale for using this preclinical model to explore targeted treatments for tongue denervation atrophy and ensuing dysphagia.A study was conducted to investigate the effects of zinc proteinate (Zn-P) on laying performance, egg quality, antioxidant indices, and egg zinc content in laying hens from 38 to 49 weeks of age. A total of 150 White Leghorn layers were randomly assigned to five treatments, each with six replicates with five birds per replication. Dietary treatments included a corn-soybean meal-based basal diet with no zinc addition and basal diet supplemented with Zn-P at 40, 80, 120, or 160 mg/kg of feed for 12 weeks. The analyzed zinc concentrations of the five diets were 29.5, 70.8, 110.2, 147.5, and 187.5 mg Zn/kg, respectively. Dietary Zn-P supplementation had no effect on feed intake and egg production. However, raising the zinc level improved egg weight (P  less then  0.01) and egg mass (P  less then  0.05) and lowered the feed conversion ratio (P  less then  0.05) during the later (46-49 weeks) period. The Zn-P supplementation also significantly (P  less then  0.05) increased Haugh units, egg shell strength, and shell thickness and had no influence on other egg quality parameters. Increasing zinc levels in the diet resulted in increase in egg zinc contents and serum zinc level. The serum triglyceride and LDL-cholesterol levels significantly decreased (P  less then  0.05) in Zn-P-supplemented groups. Supplementation of Zn-P significantly (P  less then  0.05) increased serum Cu-Zn-SOD activity and reduced MDA concentration. It could be concluded that dietary supplementation of higher levels of Zn-P, more than 80 mg/kg diet, significantly improved the egg zinc content, some egg quality traits, antioxidant activity, and serum zinc levels.Intra- and inter-specific resource partitioning within predator communities is a fundamental component of trophic ecology, and one proposed mechanism for how populations partition resources is through individual niche variation. The Niche Variation Hypothesis (NVH) predicts that inter-individual trait variation leads to functional trade-offs in foraging efficiency, resulting in populations composed of individual dietary specialists. The degree to which niche specialization persists within a population is plastic and responsive to fluctuating resource availability. We quantified niche overlap and tested the NVH within an Arctic raptor guild, focusing on three species that employ different foraging strategies golden eagles (generalists); gyrfalcons (facultative specialists); and rough-legged hawks (specialists). Tundra ecosystems exhibit cyclic populations of arvicoline rodents (lemmings and voles), providing a unique system in which to examine predator diet in response to interannual fluctuations in resource availability. Using blood δ13C and δ15N values from 189 raptor nestlings on Alaska's Seward Peninsula (2014-2019), we calculated isotopic niche width and used Bayesian stable isotope mixing models (BSIMMs) to characterize individual specialization and test the NVH. Nest-level specialization estimated from stable isotopes was strongly correlated with indices of specialization based on camera trap data. We observed a high degree of isotopic niche overlap between the three species and gyrfalcons displayed a positive relationship between individual specialization and population niche width on an interannual basis consistent with the NVH. Our findings suggest plasticity in niche specialization may reduce intra- and inter-specific resource competition under dynamic ecological conditions.

PSMA PET/MRI showed the potential to increase the sensitivity for extraprostatic disease (EPD) assessment over mpMRI; however, the interreader variability for EPD is still high. Therefore, we aimed to assess whether quantitative PSMA and mpMRI imaging parameters could yield a more robust EPD prediction.

We retrospectively evaluated PCa patients who underwent staging mpMRI and [

Ga]PSMA-PET, followed by radical prostatectomy at our institution between 01.02.2016 and 31.07.2019. Fifty-eight cases with PET/MRI and 15 cases with PET/CT were identified. EPD was determined on histopathology and correlated with quantitative PSMA and mpMRI parameters assessed by two readers ADC (mm

/1000s), longest capsular contact (LCC, mm), tumor volume (cm

), PSMA-SUV

and volume-based parameters using a fixed threshold at SUV > 4 to delineate PSMA

(g/ml) and PSMA

(cm

). The t test was used to compare means, Pearson's test for categorical correlation, and ROC curve to determine the best cutoff. Interclass correlation (ICC) was performed for interreader agreement (95% CI).

Seventy-three patients were included (64.5 ± 6.0years; PSA 14.4 ± 17.1ng/ml), and 31 had EPD (42.5%). From mpMRI, only LCC reached significance (p = 0.005), while both volume-based PET parameters PSMA

and PSMA

were significantly associated with EPD (p = 0.008 and p = 0.004, respectively). On ROC analysis, LCC, PSMA

, and PSMA

reached an AUC of 0.712 (p = 0.002), 0.709 (p = 0.002), and 0.718 (p = 0.002), respectively. ICC was moderate-good for LCC 0.727 (0.565-0.828) and excellent for PSMA

and PSMA

with 0.944 (0.990-0.996) and 0.985 (0.976-0.991), respectively.

Quantitative PSMA parameters have a similar potential as mpMRI LCC to predict EPD of PCa, with a significantly higher interreader agreement.

Quantitative PSMA parameters have a similar potential as mpMRI LCC to predict EPD of PCa, with a significantly higher interreader agreement.Pseudomonas aeruginosa (PA) is an electrogenic bacterium, in which extracellular electron transfer (EET) is mediated by microbially-produced phenazines, especially pyocyanin. Increasing EET rate in electrogenic bacteria is key for the development of biosensors and bioelectrofermentation processes. In this work, the production of pyocyanin, Nicotinamide Adenine Dinucleotide (NAD) and NAD synthetase by the electrogenic strain PA-A4 is determined using a Microbial Fuel Cell (MFC). Effects of metabolic inhibition and enhancement of pyocyanin and NAD synthetase on NAD/NADH levels and electrogenicity was demonstrated by short chronoamperometry measurements (0-48 h). Combined overexpression of two intermediate NAD synthetase production genes-nicotinic acid mononucleotide adenyltransferase (nadD) and quinolic acid phosphoribosyltransferase (nadC) genes, which are distant on the PA genomic map, enabled co-transcription and increased NAD synthetase activity. The resulting PA-A4 nadD + nadC shows increases in pyocyanin concentration, NAD synthetase activity, NAD/NADH levels, and MFC potential, all significantly higher than its wild type. Extracellular respiratory mechanisms in PA are linked with NAD metabolism, and targeted increased yield of NAD could directly lead to enhanced EET. A previous attempt at enhancing NAD synthetase for electrogenicity by targeting the terminal NAD synthetase gene (nadE) in standard P. aeruginosa PA01 had earlier been reported. Our work however, poses another route to electrogenicity enhancement in PA using; a combination of nadD and nadC. Further experiments are needed to understand specific intracellular mechanisms governing how over-expression of nadD and nadC induced activity of NadE protein. These findings significantly advance the knowledge of the versatility of NAD biosynthetic genes in PA electrogenicity.To evaluate combined effects of co-existed pesticides and nanomaterials on aquatic plants, the toxicity of herbicide atrazine (ATZ) on Iris pseudacorus in the presence and absence of Graphene oxide (GO) was investigated using chlorophyll a fluorescence transients. Results showed that GO reduced ATZ accumulation in plant. ATZ or ATZ combined with GO mainly blocked electron transport beyond QA at PSII as indicated by the sharp rise of the J-step level of fluorescence rise kinetics. The pronounced increase in Fm and the loss of I-step were observed when ATZ was at 2.0 mg·L- 1 implying the damage on the oxygen evolution complex and PSI. GO at environmentally relevant concentration did not exhibit significant photosynthetic inhibitory effects on I. pseudacorus. GO at 1.0 mg·L- 1 promoted photosynthesis of I. pseudacorus under ATZ stress at 2.0 mg·L- 1. These result indicated that the presence of GO alleviated the photosynthesis inhibition by ATZ at high levels.