👤 Bishnu Prasad Bhattarai

The effects of extruded flaxseed-pulse mixture (LinPRO-24) on growth performance, tissue fatty acid composition, carcass traits, and meat quality in broilers were investigated. A total of 540-day-old male 308 Ross chicks were placed in pens (30 chicks/pen) and allocated to three diets (n = 6) in a completely randomized design. The diets were: CON (basal corn-soybean meal diet); LPA (CON+2.5% LinPRO-24); and LPB (CON+ 5.0% LinPRO-24). Diets were isocaloric and isonitrogenous, formulated for starter (day 1-10), grower (day 11-24), and finisher (day 24-34). Feed intake and body weight (BW) were recorded daily, and mortalities as they occurred to calculate average daily gain (AWG) and FCR. On day 34, visceral organs, breast tissue, and leg tissue were sampled. The CON group exhibited higher overall BW, AWG, and AFI than LPB (P < 0.05). Breast and leg tissues of birds fed LPB had the highest concentration of Alpha-linolenic acid (ALA) and total ω-3 PUFA followed by LPA; both had a higher ALA concentration than the CON group (P < 0.05). Thus, the ω-6:ω-3 ratio in these tissues was lower for LPA and LPB groups (P < 0.05). Additionally, both LPA and LPB groups had lower Docosatetraenoic acid (DTA, C22:4 ω-6), higher Docosapentaenoic acid (DPA, C22:5 ω-3) and total PUFA content, resulting in a reduced SFA:PUFA ratio in leg tissue compared with the CON group (P < 0.05). However, LPB negatively affected the water-holding capacity (WHC) in breast meat compared with the CON and in leg tissue compared with LPA treatment (P < 0.05). Moreover, LPB increased muscle hardness and gumminess in the breast compared with the CON group (P < 0.05), thereby negatively affecting meat textural qualities. Overall, both LPA and LPB diets increased the ω-3 PUFA content in poultry meat, thereby reducing the ω-6:ω-3 ratio. However, the current study suggests that the use of LinPRO-24 at 2.5% may be more appropriate for improving the fatty acid profile of broiler meat without compromising production performance and meat quality. Show less

Angiopoietin-like 3 (ANGPTL3) is a major regulator of lipoprotein metabolism. ANGPTL3 deficiency results in lower levels of triglycerides, LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C), and may protect from cardiovascular disease. ANGPTL3 oligomerizes with ANGPTL8 to inhibit lipoprotein lipase (LPL), the enzyme responsible for plasma triglyceride hydrolysis. Independently of ANGPTL8, oligomers of ANGPTL3 can inhibit endothelial lipase (EL), which regulates circulating HDL-C and LDL-C levels through the hydrolysis of lipoprotein phospholipids. The N-terminal region of ANGPTL3 is necessary for both oligomerization and lipase inhibition. However, our understanding of the specific residues that contribute to these functions is incomplete. In this study, we performed mutagenesis of the N-terminal region to identify residues important for EL inhibition and oligomerization. We also assessed the presence of different ANGPTL3 species in human plasma. We identified a motif important for lipase inhibition, and protein structure prediction suggested that this region interacted directly with EL. We also found that recombinant ANGPTL3 formed a homotrimer and was unable to inhibit EL activity when trimerization was disrupted. Surprisingly, we observed that human plasma contained more monomeric ANGPTL3 than trimeric ANGPTL3. An important implication of these findings is that previous correlations between circulating ANGPTL3 and circulating triglyceride-rich lipoproteins need to be revisited. Show less

Ciliopathies are a group of heterogeneous disorders associated with ciliary dysfunction. Diseases in this group display considerable phenotypic variation within individual syndromes and overlapping phenotypes among clinically distinct disorders. Particularly, mutations in CEP290 cause phenotypically diverse ciliopathies ranging from isolated retinal degeneration, nephronophthisis and Joubert syndrome, to the neonatal lethal Meckel-Gruber syndrome. However, the underlying mechanisms of the variable expressivity in ciliopathies are not well understood. Here, we show that components of the BBSome, a protein complex composed of seven Bardet-Biedl syndrome (BBS) proteins, physically and genetically interact with CEP290 and modulate the expression of disease phenotypes caused by CEP290 mutations. The BBSome binds to the N-terminal region of CEP290 through BBS4 and co-localizes with CEP290 to the transition zone (TZ) of primary cilia and centriolar satellites in ciliated cells, as well as to the connecting cilium in photoreceptor cells. Although CEP290 still localizes to the TZ and connecting cilium in BBSome-depleted cells, its localization to centriolar satellites is disrupted and CEP290 appears to disperse throughout the cytoplasm in BBSome-depleted cells. Genetic interactions were tested using Cep290(rd16)- and Bbs4-null mutant mouse lines. Additional loss of Bbs4 alleles in Cep290(rd16/rd16) mice results in increased body weight and accelerated photoreceptor degeneration compared with mice without Bbs4 mutations. Furthermore, double-heterozygous mice (Cep290(+/rd16);Bbs4(+/-)) have increased body weight compared with single-heterozygous animals. Our data indicate that genetic interactions between BBSome components and CEP290 could underlie the variable expression and overlapping phenotypes of ciliopathies caused by CEP290 mutations. Show less