Anticipation in families with MLH1-associated Lynch syndrome.

Background: Lynch syndrome (LS) is an autosomal-dominant, hereditary cancer predisposition syndrome caused by pathogenic variants (PVs) in one of the mismatch-repair genes MLH1, MSH2/EPCAM, MSH6, or PMS2. Individuals who have MLH1 PVs have high lifetime risks of colorectal cancer (CRC) and endometrial cancer (EC). There is controversy regarding whether a younger age at diagnosis (or anticipation) occurs in MLH1-associated LS.

Performance of Tumor Surveillance for Children With Cancer Predisposition.

Importance: Pediatric oncology patients are increasingly recognized as having an underlying cancer predisposition syndrome (CPS). Surveillance is often recommended to detect new tumors at their earliest and most curable stages. Data on the effectiveness and outcomes of surveillance for children with CPS are limited.

Binding modes of potential anti-prion phytochemicals to PrP structures in silico.

Background: Prion diseases involve the conversion of a normal, cell-surface glycoprotein (PrP) into a misfolded pathogenic form (PrP). One possible strategy to inhibit PrP formation is to stabilize the native conformation of PrP and interfere with the conversion of PrP to PrP. Many compounds have been shown to inhibit the conversion process, however, no promising drugs have been identified to cure prion diseases.

Temperature-dependent near-surface interstitial segregation in niobium.

Niobium's superconducting properties are affected by the presence and precipitation of impurities in the near-surface region. A systematic wide-temperature range x-ray diffraction study is presented addressing the effect of low temperatures (108 K-130 K) and annealing treatments (523 K in nitrogen atmosphere, 400 K in UHV) on the near-surface region of a hydrogen-loaded Nb(100) single-crystal. Under these conditions, the response of the natural surface oxides (NbO, NbO, and NbO) and the changes in the subsurface concentration of interstitial species in Nb are explored, thereby including the cryogenic temperature regime relevant for device operation.

A novel frameshift mutation in the gene in a patient with Lynch syndrome.

A novel mutation in the MLH1 gene likely to be pathogenic for Lynch syndrome was discovered in a proband with a family history of colon cancer. Immunohistochemistry showed negative expression of PMS2 and MLH1 in the resected tumor sample. The mutation lies at the highly conserved C-terminus of the MLH1 protein, the region through which it dimerizes with PMS2 to carry out its mismatch repair function.

Proximate and mineral composition of Kadamba () fruit and its use in the development of nutraceutical enriched beverage.

, commonly known as Kadamba, is one of the economically important trees, which is being exploited for paper, pulp and wood industries, however uses of its fruits are not reported. In the present investigation the fruits were analysed for their proximate and mineral content at different stages of maturity, and the ripe fruit was used for nectar preparation. Proximate analysis of the ripe edible fruit showed that it is rich in fat (2.

Phytochemical composition, in vitro antioxidant activity and antibacterial mechanisms of Neolamarckia cadamba fruits extracts.

Aqueous extracts of Neolamarckia cadamba fruits prepared at different maturity stages were used for the analysis of various phytochemicals, and their antioxidant and antibacterial activities were determined. Ripe fruit extract had highest phenolics (3.14 mM GAE/ g fruit extract) with caffeic acid, tannic acid, syringic acid and quercetin as major phenolic compounds.

Traditional uses, phytochemistry and pharmacological properties of Neolamarckia cadamba: A review.

Ethnopharmacological Relevance: There are more than 3000 officially documented plants in the Indian subcontinent that hold great medicinal potential. One such under-explored plant is an evergreen tropical tree Neolamarckia cadamba (Roxb.) Bosser (Rubiaceae).

Nicotine exposure, blood pressure, and inflammation in tobacco smokers and chewers in a rural community in Nepal.

Tobacco consumption is high amongst the people of Xxx. This study was carried out in 2011 in a rural community of Xxx, to compare pathological parameters associated with tobacco use in relation to nicotine metabolism between smokers, chewers, and a control group. A total of 216 volunteers provided blood and urine samples for testing nicotine metabolites, C-reactive protein, and cell counts.

Roles of the redox-active disulfide and histidine residues forming a catalytic dyad in reactions catalyzed by 2-ketopropyl coenzyme M oxidoreductase/carboxylase.

NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC), an atypical member of the disulfide oxidoreductase (DSOR) family of enzymes, catalyzes the reductive cleavage and carboxylation of 2-ketopropyl-coenzyme M [2-(2-ketopropylthio)ethanesulfonate; 2-KPC] to form acetoacetate and coenzyme M (CoM) in the bacterial pathway of propylene metabolism. Structural studies of 2-KPCC from Xanthobacter autotrophicus strain Py2 have revealed a distinctive active-site architecture that includes a putative catalytic triad consisting of two histidine residues that are hydrogen bonded to an ordered water molecule proposed to stabilize enolacetone formed from dithiol-mediated 2-KPC thioether bond cleavage. Site-directed mutants of 2-KPCC were constructed to test the tenets of the mechanism proposed from studies of the native enzyme.

Selection criteria and pre-clinical academic performance in a private medical college in Nepal: a case study.

Background: All medical schools in Nepal use academic merit as the criterion for selecting students. Medical educationists in Nepal seek to make the selection process more transparent and fair to applicants from different socio-economic backgrounds, while striving to raise the educational standards.

Aim: To evaluate the efficacy of selection methods in relation to academic success.

Structural basis for carbon dioxide binding by 2-ketopropyl coenzyme M oxidoreductase/carboxylase.

The structure of 2-ketopropyl coenzyme M oxidoreductase/carboxylase (2-KPCC) has been determined in a state in which CO(2) is observed providing insights into the mechanism of carboxylation. In the substrate encapsulated state of the enzyme, CO(2) is bound at the base of a narrow hydrophobic substrate access channel. The base of the channel is demarcated by a transition from a hydrophobic to hydrophilic environment where CO(2) is located in position for attack on the carbanion of the ketopropyl group of the substrate to ultimately produce acetoacetate.

Metabolic disease in Nepal: a perspective.

Inborn errors of metabolism or metabolic diseases, are a group of genetically determined metabolic disorders that result in mental retardation or early death. The prevalence of IEM in various countries shows a prevalence varying between 1 in 800 to 1 in 5000. As the technology for detecting metabolites has become more advanced, studies utilizing more modern methods report a higher prevalence.

Neurootological differentiations in endogenous tinnitus.

Vertigo and tinnitus are very frequent complaints. Often, we find multisensory syndromes combined with tinnitus, hearing impairment, vertigo, and nausea. From more than 10,000 cases, we evaluated 757 randomly selected neurootological patients suffering from endogenous tinnitus.

Dithiomethylether as a ligand in the hydrogenase h-cluster.

An X-ray crystallographic refinement of the H-cluster of [FeFe]-hydrogenase from Clostridium pasteurianum has been carried out to close-to atomic resolution and is the highest resolution [FeFe]-hydrogenase presented to date. The 1.39 A, anisotropically refined [FeFe]-hydrogenase structure provides a basis for examining the outstanding issue of the composition of the unique nonprotein dithiolate ligand of the H-cluster.

Mechanistic implications of the structure of the mixed-disulfide intermediate of the disulfide oxidoreductase, 2-ketopropyl-coenzyme M oxidoreductase/carboxylase.

The structure of the mixed, enzyme-cofactor disulfide intermediate of ketopropyl-coenzyme M oxidoreductase/carboxylase has been determined by X-ray diffraction methods. Ketopropyl-coenzyme M oxidoreductase/carboxylase belongs to a family of pyridine nucleotide-containing flavin-dependent disulfide oxidoreductases, which couple the transfer of hydride derived from the NADPH to the reduction of protein cysteine disulfide. Ketopropyl-coenzyme M oxidoreductase/carboxylase, a unique member of this enzyme class, catalyzes thioether bond cleavage of the substrate, 2-ketopropyl-coenzyme M, and carboxylation of what is thought to be an enzyme-stabilized enolacetone intermediate.

A comparison of phosphonothioic acids with phosphonic acids as phosphatase inhibitors.

Phosphorothioates, analogues of phosphate esters in which a sulfur replaces an oxygen atom in the phosphoryl group, are competent surrogate substrates for a number of phosphatases. In some cases the thio analogues show similar binding (as estimated by K(m)) while other phosphatases show quite different K(m) values for phosphate compared to phosphorothioate esters. On this basis it was hypothesized that there might be different inhibitory tendencies by the nonhydrolyzable analogues, phosphonothioic acids compared with phosphonic acids.