Project description:The Aster-C protein (encoded by the Gramd1c gene) is an endoplasmic reticulum (ER) resident protein that has been reported to transport cholesterol from the plasma membrane to the ER . Although there is a clear role for the closely-related Aster-B protein in cholesterol transport and downstream esterification in the adrenal gland, the specific role for Aster-C in tissue cholesterol homeostasis is not well understood. Here, we have examined whole body cholesterol balance in mice globally lacking Aster-C under low or high dietary cholesterol conditions.transport and metabolism under divergent dietary cholesterol conditions. These results strongly suggest that Aster-C alone is not sufficient to control whole body cholesterol balance, but can modestly impact circulating cortisol and bile acid levels when dietary cholesterol is limited.
Project description:Here we describe a genome-wide analysis of copy number variations (CNVs) in Chinese domestic cattle by using array comparative genomic hybridization (array CGH) and quantitative PCR (qPCR). We conducted array CGH analysis on 30 male cattle individuals, animals from consisting of 12 breeds of Bos taurus/Bos indicus, 1 Bos grunniens and and two ones of Bubalus bubalis breeds for with beef, and/or dairy or dual purpose. We identified over 470 candidate CNV regions (CNVRs) in Bos B. taurus/B. indicus; 118 candidate CNV regions (CNVRs) in B. grunniens, 139 CNVRs in B. bubalis. Furthermore, based on the Y haplotypes of B. taurus/ B. indicus, Wwe also identified 69, 337, and 251 candidate CNV regions (CNVRs) in the sub-groups of Y1, Y2 and Y3 haplotypes.
Project description:Background: The Malnad Gidda are unique dwarf Bos indicus cattle native to heavy rainfall Malnad and coastal areas of Karnataka in India. These cattle are highly adapted to harsh climatic conditions and are more resistant to Foot and Mouth disease as compared to other breeds of B.indicus. Since the first genome reference became available from B.taurus Hereford breed, only a few other breeds have been genotyped using high-throughput platforms. Also despite the known reports on high diversity within indicine breeds as compared to taurine breeds, only one draft genome of Nellore and horn transcriptome of Kankrej breed were sequenced at base level resolution. Because of the special characteristics Malnad Gidda possess, it becomes the choice of breed among many indicine cows to study at molecular level and genotyping. Results: Sequencing mRNA from the PBMCs isolated from blood of one selected Malnad Gidda bull resulted in generation of 55 million paired-end reads of 100bp length. Raw sequencing data is processed to trim the adaptor and low quality bases, and are aligned against the whole genome and transcript assemblies of Bos taurus UMD 3.1 and Bos indicus (Nellore breed) respectively. About 72% of the sequenced reads from our study could be mapped against the B.taurus genome where as only 41% of reads could be mapped against the Bos indicus transcript assembly. Transcript assembly from the alignment carried out against the annotated B.taurus UMD 3.1 genome resulted in identification of ~10,000 genes with significant expression (FPKM>1). In a similar analysis against the B.indicus Kankrej assembled transcripts we could identify only ~6,000 transcripts. From the variant analysis of the sequencing data we found ~10,000 SNPs in coding regions among which ~9,000 are novel and ~6,400 are amino acid changing. Conclusions: For the first time we have genotyped and explored the transcriptome of B.indicus Malnad Gidda breed. A comparative analysis of mapping the RNA-Seq data against the available reference genome and transcript sequences is demonstrated. An enhanced utility of transcript sequencing could be achieved by improving or completing the sequence assembly of any B.indicus breed to better characterize the indicine breeds for productivity features and selective breeding.
Project description:The coordination of chloroplast and nuclear genome status are critical for plant cell function, but the mechanism remain largely unclear. In this study, we report that Arabidopsis thaliana CHLOROPLAST AND NUCLEUS DUAL-LOCALIZED PROTEIN 1 (CND1) maintains genome stability in both the chloroplast and the nucleus.
Project description:Intestinal cholesterol absorption is an important determinant of systemic cholesterol homeostasis. Niemann-Pick C1 Like 1 (NPC1L1), the target of the drug ezetimibe, is a critical player in dietary cholesterol uptake. But how cholesterol moves within the cell downstream of NPC1L1 is unknown. Here we show that the nonvesicular sterol transporters Aster-B and -C cooperate with NPC1L1 to deliver dietary cholesterol from the gut lumen to the enterocyte ER for chylomicron packaging. Aster proteins are recruited to the enterocyte plasma membrane (PM) in response to NPC1L1-dependent cholesterol accumulation. Mice lacking Asters in intestine have impaired cholesterol absorption, and reduced plasma cholesterol. NanoSIMS imaging and tracer studies reveal delayed lipid trafficking into chylomicrons in Aster-deficient enterocytes. Interestingly, in addition to potently blocking NPC1L1, ezetimibe is also a low-affinity inhibitor of Aster-B and -C but not -A, and the structure of the Aster-C-ezetimibe complex reveals the basis for this selectivity. Our findings support a model in which NPC1L1 enriches dietary cholesterol at the apical PM, and ASTERs subsequently traffic this cholesterol to the ER. The findings identify the enterocyte Aster pathway as potential target for treatment of hypercholesterolemia. Alessandra Ferrari, PhD