A note on ensiling characteristics of the tropical grass Setaria sphacelata var. splendida (Stapf).

The objective of this study was to evaluate the ensiling characteristics of Setaria sphacelata var. splendida (S. splendida) and to identify ensilability limiting factors of this tropical grass, locally produced

Role of a family 11 carbohydrate-binding module in the function of a recombinant cellulase used to supplement a barley based diet for broiler chickens

Cellulases and xylanases display a modular architecture that comprises a catalytic module linked to one or more non-catalytic carbohydrate-binding modules (CBMs). CBMs have been classified into 52 different families, based on primary structure similarity. These non-catalytic modules mediate a prolonged and intimate contact of the enzyme with the target substrate eliciting efficient hydrolysis of the target polysaccharides. 2. A study was undertaken to investigate the importance of a family 11 CBM, displaying high affinities for barley -glucans, in the function of recombinant derivatives of cellulase CtLic26A-Cel5E of Clostridium thermocellum used to supplement a barley-based diet for broiler chicken. 3. The results showed that birds fed on diets containing the recombinant CtLic26A-Cel5E modular derivatives or the commercial enzyme mixture RovabioTM Excel AP displayed improved performance when compared with birds fed on diets not supplemented with exogenous enzymes. 4. It is suggested that the enzyme dosage used in this study (30 U/kg of basal diet), was probably too high for the efficacy of the family 11 CBM to be noticed. It remains to be established if the targeting effect resulting from the incorporation of CBMs in plant cell wall hydrolases may be effective at lower exogenous enzyme dosages

Crop -glucanase activity limits the effectiveness of a recombinant cellulase used to supplement a barley-based feed for free-range broilers

1. The supplementation of diets rich in soluble polysaccharides with microbial cellulases and hemicellulases decreases digesta viscosity and promotes broiler performance. 2. In contrast, recent experiments suggest that polysaccharidases are ineffective for improving the nutritive value of pasture biomass used by free-range broilers. However, the feasibility of using cellulases and hemicellulases to improve the utilisation of cereal-based feeds by pastured poultry remains to be established. 3. A study was undertaken to investigate the capacity of a recombinant cellulase from Clostridium thermocellum to improve the nutritive value of a barley-based feed for free-range pastured broilers of the RedBro Cou Nu RedBro M genotype. 4. The results show that supplementation of a barley-based diet with a recombinant -glucanase had no effect on the performance of free-range broilers, foraging in legume-based diets from d 28 to 56. In addition, the results confirm that the lack of effect of the recombinant enzyme in improving the nutritive value of the barley-based feed does not result from enzyme proteolysis or inhibition in the gastrointestinal tract. 5. Significantly, -glucanase activity was identified in the crop of non-supplemented animals. The data suggest that endogenous cellulases originated both from the barley-based feed and from the crop microflora. 6. The results presented here suggest that in older birds of slow-growing genotypes associated with free-range production systems, previously unknown sources of -glucanases, such as the feed and microbial symbiotic microflora, can affect the effectiveness of exogenous enzymes added to the feed

Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies

Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype