Genetics of acute and chronic pancreatitis: An update

Progress made in identifying the genetic susceptibility underlying acute and chronic pancreatitis has benefitted the clinicians in understanding the pathogenesis of the disease in a better way. The identification of mutations in cationic trypsinogen gene(PRSS1 gene; functional gain mutations) and serine protease inhibitor kazal type 1(SPINK1 gene; functional loss mutations) and other potential susceptibility factors in genes that play an important role in the pancreatic secretory functions or response to inflammation during pancreatic injury has changed the current concepts and understanding of a complex multifactorial disease like pancreatitis. An indi-vidual's susceptibility to the disease is governed by ge-netic factors in combination with environmental factors. Candidate gene and genetic linkage studies have iden-tified polymorphisms in cationic trypsinogen(PRSS1), SPINK1, cystic fibrosis trans-membrane conductance regulator(CFTR), Chymotrypsinogen C(CTRC), Ca-thepsin B(CTSB) and calcium sensing receptor(CASR). Individuals with polymorphisms in the mentioned genes and other as yet identified genes are at an enhanced risk for the disease. Recently, polymorphisms in genes other than those involved in "intra-pancreatic trypsin regulatory mechanism" namely Claudin-2(CLDN2) andCarboxypeptidase A1(CPA1) gene have also been iden-tified for their association with pancreatitis. With ever growing number of studies trying to identify the genetic susceptibility in the form of single nucleotide polymor-phisms, this review is an attempt to compile the avail-able information on the topic.     

Long-range patterns of diversity and linkage disequilibrium surrounding the maize Y1 gene are indicative of an asymmetric selective sweep

Both yellow and white corn occurs among ancestral open pollinated varieties. More recently, breeders have selected yellow endosperm variants of maize over ancestral white phenotypes for their increased nutritional value resulting from the up-regulation of the Y1 phytoene synthase gene product in endosperm tissue. As a result, diversity within yellow maize lines at the Y1 gene is dramatically decreased as compared to white corn. We analyzed patterns of sequence diversity and linkage disequilibrium in nine low copy regions located at varying distances from the Y1 gene, including a homolog of the barley Mlo gene. Patterns consistent with a selective sweep, such as significant associations of informative single-nucleotide polymorphisms with endosperm color phenotype, linkage disequilibrium, and significantly reduced diversity within the yellow endosperm haplotypes, were observed up to 600 kb downstream of Y1, whereas the upstream region showed a more rapid recovery. The starch branching enzyme 1 (sbe1) gene is the first region downstream of Y1 that does not have a highly conserved haplotype in the yellow endosperm germplasm.     

The utilization of protein from a low-protein diet as determined by limiting essential amino acids

Protein utilization was determined by assay with low-protein diets limiting in one of nine essential amino acids. The diets contained 50 g protein/kg and the amino acid score of the protein was 0.50. Protein utilization was found to be related to the particular limiting essential amino acids present. The usefulness of Bender's (1965) standard amino acid requirement for the estimation of amino acid utilization from a low-protein diet is discussed.     

Enteroendocrine K Cells Exert Complementary Effects to Control Bone Quality and Mass in Mice

The involvement of a gut-bone axis in controlling bone physiology has been long suspected, although the exact mechanisms are unclear. We explored whether glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine K cells were involved in this process. The bone phenotype of transgenic mouse models lacking GIP secretion (GIP-GFP-KI) or enteroendocrine K cells (GIP-DT) was investigated. Mice deficient in GIP secretion exhibited lower bone strength, trabecular bone mass, trabecular number, and cortical thickness, notably due to higher bone resorption. Alterations of microstructure, modifications of bone compositional parameters, represented by lower collagen cross-linking, were also apparent. None of these alterations were observed in GIP-DT mice lacking enteroendocrine K cells, suggesting that another K-cell secretory product acts to counteract GIP action. To assess this, stable analogues of the known K-cell peptide hormones, xenin and GIP, were administered to mature NIH Swiss male mice. Both were capable of modulating bone strength mostly by altering bone microstructure, bone gene expression, and bone compositional parameters. However, the two molecules exhibited opposite actions on bone physiology, with evidence that xenin effects are mediated indirectly, possibly via neural networks. Our data highlight a previously unknown interaction between GIP and xenin, which both moderate gut-bone connectivity. © 2020 American Society for Bone and Mineral Research.     

Non-invasive real-time assessment of hepatic macrovesicular steatosis in liver donors:Hypothesis,design and proof-of-concept study

Macrovesicular Steatosis(MS) is an independent risk factor for adverse post-liver transplant(LT) outcomes. The degree of MS is intimately related to the viability of the liver graft, which in turn is crucial to the success of the operation. An ideal liver graft should have no MS and most centres would find it unacceptable to use a donor liver with severe MS for LT. While a formal liver biopsy is the goldstandard diagnostic test for MS, given the logistical and time constraints it is not universally feasible. Other tests like a frozen section biopsy are plagued by issues of fallibility with reporting and sampling bias making them inferior to a liver biopsy. Hence, the development of an accurate, non-invasive, easy-to-use,handheld, real-time device for quantification of MS would fill this lacuna in the deceased donor selection process. We present the hypothesis, design and proof-ofconcept of a study, which aims to standardise and determine the feasibility and accuracy of a novel handheld device applying the principle of diffuse reflectance spectroscopy for real-time quantification of MS.