Novel combination of feed enzymes to improve the degradation of Chlorella vulgaris recalcitrant cell wall

Research Areas: Science & TechnologyABSTRACT - In this study, a rational combination of 200 pre-selected Carbohydrate-Active enzymes (CAZymes) and sulfatases were tested, individually or combined, according to their ability to degrade Chlorella vulgaris cell wall to access its valuable nutritional compounds. The disruption of microalgae cell walls by a four enzyme mixture (Mix) in comparison with the control, enabled to release up to 1.21g/L of reducing sugars (p<0.001), led to an eight-fold increase in oligosaccharides release (p<0.001), and reduced the fuorescence intensity by 47% after staining with Calcofuor White (p<0.001). The Mix treatment was successful in releasing proteins (p<0.001), some MUFA (p<0.05), and the benefcial 18:3n-3 fatty acid (p0.05), total carotenoids were increased in the supernatant (p<0.05) from the Mix treatment, relative to the control. Taken together, these results indicate that this four-enzyme Mix displays an efective capacity to degrade C. vulgaris cell wall. Thus, these enzymes may constitute a good approach to improve the bioavailability of C. vulgaris nutrients for monogastric diets, in particular, and to facilitate the cost-efective use of microalgae by the feed industry, in general.info:eu-repo/semantics/publishedVersio

Joint Genetic Analysis of Gene Expression Data with Inferred Cellular Phenotypes

Even within a defined cell type, the expression level of a gene differs in individual samples. The effects of genotype, measured factors such as environmental conditions, and their interactions have been explored in recent studies. Methods have also been developed to identify unmeasured intermediate factors that coherently influence transcript levels of multiple genes. Here, we show how to bring these two approaches together and analyse genetic effects in the context of inferred determinants of gene expression. We use a sparse factor analysis model to infer hidden factors, which we treat as intermediate cellular phenotypes that in turn affect gene expression in a yeast dataset. We find that the inferred phenotypes are associated with locus genotypes and environmental conditions and can explain genetic associations to genes in trans. For the first time, we consider and find interactions between genotype and intermediate phenotypes inferred from gene expression levels, complementing and extending established results

Nos2 Inactivation Promotes the Development of Medulloblastoma in Ptch1+/− Mice by Deregulation of Gap43–Dependent Granule Cell Precursor Migration

Medulloblastoma is the most common malignant brain tumor in children. A subset of medulloblastoma originates from granule cell precursors (GCPs) of the developing cerebellum and demonstrates aberrant hedgehog signaling, typically due to inactivating mutations in the receptor PTCH1, a pathomechanism recapitulated in Ptch1+/− mice. As nitric oxide may regulate GCP proliferation and differentiation, we crossed Ptch1+/− mice with mice lacking inducible nitric oxide synthase (Nos2) to investigate a possible influence on tumorigenesis. We observed a two-fold higher medulloblastoma rate in Ptch1+/− Nos2−/− mice compared to Ptch1+/− Nos2+/+ mice. To identify the molecular mechanisms underlying this finding, we performed gene expression profiling of medulloblastomas from both genotypes, as well as normal cerebellar tissue samples of different developmental stages and genotypes. Downregulation of hedgehog target genes was observed in postnatal cerebellum from Ptch1+/+ Nos2−/− mice but not from Ptch1+/− Nos2−/− mice. The most consistent effect of Nos2 deficiency was downregulation of growth-associated protein 43 (Gap43). Functional studies in neuronal progenitor cells demonstrated nitric oxide dependence of Gap43 expression and impaired migration upon Gap43 knock-down. Both effects were confirmed in situ by immunofluorescence analyses on tissue sections of the developing cerebellum. Finally, the number of proliferating GCPs at the cerebellar periphery was decreased in Ptch1+/+ Nos2−/− mice but increased in Ptch1+/− Nos2−/− mice relative to Ptch1+/− Nos2+/+ mice. Taken together, these results indicate that Nos2 deficiency promotes medulloblastoma development in Ptch1+/− mice through retention of proliferating GCPs in the external granular layer due to reduced Gap43 expression. This study illustrates a new role of nitric oxide signaling in cerebellar development and demonstrates that the localization of pre-neoplastic cells during morphogenesis is crucial for their malignant progression

Dynamic purine signaling and metabolism during neutrophil–endothelial interactions

During episodes of hypoxia and inflammation, polymorphonuclear leukocytes (PMN) move into underlying tissues by initially passing between endothelial cells that line the inner surface of blood vessels (transendothelial migration, TEM). TEM creates the potential for disturbances in vascular barrier and concomitant loss of extravascular fluid and resultant edema. Recent studies have demonstrated a crucial role for nucleotide metabolism and nucleoside signaling during inflammation. These studies have implicated multiple adenine nucleotides as endogenous tissue protective mechanisms invivo. Here, we review the functional components of vascular barrier, identify strategies for increasing nucleotide generation and nucleoside signaling, and discuss potential therapeutic targets to regulate the vascular barrier during inflammation

Autophagy as a modulator and target in prostate cancer

Autophagy, or “self eating,” is an adaptive process that helps cells cope with metabolic, toxic, and even infectious stressors. While the adaptive capability of autophagy is generally beneficial, autophagy can also facilitate enhanced nutrient utilization and improved growth characteristics in cancer cells. Moreover, autophagy can promote greater cellular robustness in the context of therapeutic intervention. This has proven to be the case in advanced prostate cancer, where preclinical data largely supports that autophagy facilitates both disease progression and therapeutic resistance. Notably, androgen deprivation therapy, taxane-based chemotherapy, targeted kinase inhibition, and nutrient restriction all induce significant cellular distress. Autophagy is subsequently up-regulated through core metabolic regulatory signaling cascades (i.e. AMPK, PI3K, and mTOR), and more favorable growth and nutrient conditions are established. Current research also demonstrates that when the autophagic machinery is inhibited, greater cell killing and tumor responsiveness can be obtained. In this review, we will cover current prostate cancer treatments associated with alterations in autophagy; data supporting autophagic modulation with added emphasis on alterations occurring within prostate cancer models; and finally, research supporting adjuvant autophagic modulation with current prostate cancer treatment paradigms