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11.
The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs. 相似文献
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A recently silenced, duplicate PgiC locus in Clarkia 总被引:1,自引:0,他引:1
Previous electrophoretic analysis showed that 17 diploid species of the
wildflower Clarkia (Onagraceae) have two cytosolic isozymes of
phosphoglucose isomerase (PGIC; EC 5.3.1.9), whereas 15 other diploid
species have a single PGIC. Molecular studies revealed that the two
isozymes in the former species are encoded by duplicate genes, PgiC1 and
PgiC2, whereas the single isozyme in the latter is always encoded by PgiC1.
Phylogenetic analysis of the nucleotide sequences implied that PgiC2 was
silenced four times independently in the genus. Here we describe a psi
PgiC2 from C. mildrediae, a species in which only PgiC1 is expressed. The
discovery of the psi PgiC2 is significant because it confirms a formal
prediction of the phylogenetic analysis. The psi PgiC2 includes 5,039
nucleotides corresponding to 18 of the 23 exons of PgiC, as well as the
intervening introns and 3' nontranslated region. The absence of an increase
of nucleotide substitutions in its "exons" suggests that the gene was
silenced recently. The present study appears to be the first to establish
that a specific duplicate gene locus regularly expressed in a group of
related plant species has been silenced in one of them. The multiple
independent silencings of PgiC2 suggest that it remained functional but
inessential in ancestral lineages. We discuss the possibility that PgiC2
may have been preserved in these lineages by selection against mutants
causing defective PGIC1- PGIC2 heterodimers.
相似文献
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Kalicharan Sharma Omprakash Tanwar Girdhar Singh Deora S. Ali M.M. Alam M.S. Zaman Vagolu Siva Krishna Dharmarajan Sriram Mymoona Akhter 《Bioorganic & medicinal chemistry》2019,27(7):1421-1429
A series of 1-(1-benzyl-2-methyl-5-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)-1H-indol-3-yl)ethanone and ethyl 1-benzyl-2-methyl-5-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)-1H-indole-3-carboxylate derivatives were designed based on bioisosteric replacement of previously reported antitubercular agent (IND-07). Twenty ligands were successfully synthesized and some of them were found to have good in vitro activity (MIC?<?10?μM) against the H37Rv strain of Mycobacterium tuberculosis. Among these compounds, KC-08 and KC-11 inhibited Mtb-DHFR with 4- and 18-fold selectivity for Mtb-DHFR over h-DHFR, respectively. Compound KC-11 display acceptable ADME, and better pharmacokinetic profiles than IND-07. Docking studies were performed to predict the binding mode of the compounds within the active site of Mtb-DHFR and h-DHFR. The results of our study suggest that compound KC-11 may serve as a valuable lead for the design and development of selective inhibitors of Mtb-DHFR with potential therapeutic application in tuberculosis. 相似文献
16.
Nicholas?M?Chesarino Jocelyn?C?Hach James?L?Chen Balyn?W?Zaro Murugesan?VS?Rajaram Joanne?Turner Larry?S?Schlesinger Matthew?R?Pratt Howard?C?Hang Jacob?S?YountEmail author 《BMC biology》2014,12(1):91
Background
Palmitoylation is a 16-carbon lipid post-translational modification that increases protein hydrophobicity. This form of protein fatty acylation is emerging as a critical regulatory modification for multiple aspects of cellular interactions and signaling. Despite recent advances in the development of chemical tools for the rapid identification and visualization of palmitoylated proteins, the palmitoyl proteome has not been fully defined. Here we sought to identify and compare the palmitoylated proteins in murine fibroblasts and dendritic cells.Results
A total of 563 putative palmitoylation substrates were identified, more than 200 of which have not been previously suggested to be palmitoylated in past proteomic studies. Here we validate the palmitoylation of several new proteins including Toll-like receptors (TLRs) 2, 5 and 10, CD80, CD86, and NEDD4. Palmitoylation of TLR2, which was uniquely identified in dendritic cells, was mapped to a transmembrane domain-proximal cysteine. Inhibition of TLR2 S-palmitoylation pharmacologically or by cysteine mutagenesis led to decreased cell surface expression and a decreased inflammatory response to microbial ligands.Conclusions
This work identifies many fatty acylated proteins involved in fundamental cellular processes as well as cell type-specific functions, highlighting the value of examining the palmitoyl proteomes of multiple cell types. S-palmitoylation of TLR2 is a previously unknown immunoregulatory mechanism that represents an entirely novel avenue for modulation of TLR2 inflammatory activity.17.
Germline mutations of the Liver Kinase b1 (LKB1/STK11) tumor suppressor gene have been linked to Peutz-Jeghers Syndrome (PJS), an autosomal-dominant, cancer-prone disorder in which patients develop neoplasms in several organs, including the oviduct, ovary, and cervix. We have conditionally deleted Lkb1 in Müllerian duct mesenchyme-derived cells of the female reproductive tract and observed expansion of the stromal compartment and hyperplasia and/or neoplasia of adjacent epithelial cells throughout the reproductive tract with paratubal cysts and adenomyomas in oviducts and, eventually, endometrial cancer. Examination of the proliferation marker phospho-histone H3 and mammalian Target Of Rapamycin Complex 1 (mTORC1) pathway members revealed increased proliferation and mTORC1 activation in stromal cells of both the oviduct and uterus. Treatment with rapamycin, an inhibitor of mTORC1 activity, decreased tumor burden in adult Lkb1 mutant mice. Deletion of the genes for Tuberous Sclerosis 1 (Tsc1) or Tsc2, regulators of mTORC1 that are downstream of LKB1 signaling, in the oviductal and uterine stroma phenocopies some of the defects observed in Lkb1 mutant mice, confirming that dysregulated mTORC1 activation in the Lkb1-deleted stroma contributes to the phenotype. Loss of PTEN, an upstream regulator of mTORC1 signaling, along with Lkb1 deletion significantly increased tumor burden in uteri and induced tumorigenesis in the cervix and vagina. These studies show that LKB1/TSC1/TSC2/mTORC1 signaling in mesenchymal cells is important for the maintenance of epithelial integrity and suppression of carcinogenesis in adjacent epithelial cells. Because similar changes in the stromal population are also observed in human oviductal/ovarian adenoma and endometrial adenocarcinoma patients, we predict that dysregulated mTORC1 activity by upstream mechanisms similar to those described in these model systems contributes to the pathogenesis of these human diseases. 相似文献
18.
Some non-protein α-amino acids were derivatized with 1-fluoro-2,4-dinitrophenyl-5-l-alaninamide (Marfey’s reagent, MR, FDNP-l-Ala-NH2,) and four of its structural variants FDNP-l-Phe-NH2, FDNP-l-Val-NH2, FDNP-l-Leu-NH2 and FDNP-l-Pro-NH2. The resultant diastereomers were separated by normal and reversed phase thin layer chromatography (TLC) and reversed phase
HPLC. In normal phase TLC, best resolution was obtained with solvent combination of phenol-water (3:1) while in reversed phase
TLC mixtures of acetonitrile with triethylammonium phosphate buffer were found successful for resolution of diastereomers.
The separation behavior of diastereomers prepared with different reagents was compared. The diastereomers of most of the amino
acids prepared with FDNP-l-Leu-NH2 were best separated while those prepared with FDNP-l-Pro-NH2 failed to separate in most of the cases. The diastereomers were also separated on a reversed phase C8 column with gradient elution using mixture of aqueous-trifluoroacetic acid (TFA) and acetonitrile and with detection at 340 nm.
The effects of TFA concentration, flow rate and run time on HPLC separation were studied. 相似文献
19.
Aulus EAD Barbosa Érika VS Albuquerque Maria CM Silva Djair SL Souza Osmundo B Oliveira-Neto Arnubio Valencia Thales L Rocha Maria F Grossi-de-Sa 《BMC biotechnology》2010,10(1):44
Background
Coffee is an important crop and is crucial to the economy of many developing countries, generating around US70 billion per year. There are 115 species in the < i > Coffea < /i > genus, but only two, < i > C. arabica < /i > and < i > C. canephora < /i > , are commercially cultivated. Coffee plants are attacked by many pathogens and insect-pests, which affect not only the production of coffee but also its grain quality, reducing the commercial value of the product. The main insect-pest, the coffee berry borer ( < i > Hypotheneumus hampei < /i > ), is responsible for worldwide annual losses of around US70 billion per year. There are 115 species in the Coffea genus, but only two, C. arabica and C. canephora, are commercially cultivated. Coffee plants are attacked by many pathogens and insect-pests, which affect not only the production of coffee but also its grain quality, reducing the commercial value of the product. The main insect-pest, the coffee berry borer (Hypotheneumus hampei), is responsible for worldwide annual losses of around US500 million. The coffee berry borer exclusively damages the coffee berries, and it is mainly controlled by organochlorine insecticides that are both toxic and carcinogenic. Unfortunately, natural resistance in the genus Coffea to H. hampei has not been documented. To overcome these problems, biotechnological strategies can be used to introduce an α-amylase inhibitor gene (α-AI1), which confers resistance against the coffee berry borer insect-pest, into C. arabica plants. 相似文献20.
A Cl- and NO3- insensitive oxalate oxidase, purified from the roots of 10-day old seedlings of grain Sorghum has been immobilized on polyvinyl alcohol (PVA) membrane through entrapment with 96.07% retention of initial activity. The membrane bound enzyme showed an increase in optimum pH (from 5.0 to 6.5), time of incubation (from 5 to 10 min) and Km for oxalate (from 0.38 to 6.23 mM), but decrease in incubation temperature for maximum activity (from 37 to 30 degrees C) and Vmax (from 70 nmol/min/ml to 9.7 nmol H2O2/min) and was unaffected by Cl- and NO3. The membrane bound enzyme lost 50% of its initial activity after 30 days of storage at room temperature. The use of membrane bound oxalate oxidase in determination of serum oxalate of urinary stone patients is demonstrated. 相似文献