MSH6, a Saccharomyces cerevisiae protein that binds to mismatches as a heterodimer with MSH2

The process of post-replicative DNA-mismatch repair seems to be highly evolutionarily conserved. In Escherichia coli, DNA mismatches are recognized by the MutS protein. Homologues of the E. coli mutS and mutL mismatch-repair genes have been identified in other prokaryotes, as well as in yeast and mammals. Recombinant Saccharomyces cerevisiae MSH2 (MSH for MutS homologue) and human hMSH2 proteins have been shown to bind to mismatch-containing DNA in vitro. However, the physiological role of hMSH2 is unclear, as shown by the recent finding that the mismatch-binding factor hMutS alpha isolated from extracts of human cells is a heterodimer of hMSH2 and another member of the MSH family, GTBP. It has been reported that S. cerevisiae possesses a mismatch-binding activity, which most probably contains MSH2. We show here that, as in human cells, the S. cerevisiae binding factor is composed of MSH2 and a new functional MutS homologue, MSH6, identified by its homology to GTBP.     

RS-17053 (N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl-1H-indole-3-ethanamine hydrochloride), a selective alpha 1A-adrenoceptor antagonist, displays low affinity for functional alpha 1-adrenoceptors in human prostate: implications for adrenoceptor classification

Hereditary developmental abnormalities of the upper or lower limbs in humans are easily recognizable phenotypes that can be used in the mapping and cloning of genes involved in normal human development. We studied a large Indian pedigree (UR002) with an autosomal dominant triphalangeal thumb (TPT) and polysyndactyly (PSD). The abnormalities were present only in the upper limbs, and the phenotype was fully penetrant. The expression of the phenotype was variable and ranged from unilateral TPT to bilateral TPT, preaxial du-, tri-, or quadruplication of the thumb, or syndactyly of multiple thumbs. There were 112 affected individuals in the pedigree. Previous linkage analyses on apparently similar phenotypes have identified a locus at 7q36 [Heutink et al., 1994, Nature Genet 6:287-291; Tsukurov et al., 1994]. To map the gene responsible for the TPT-PSD in family UR002, we performed linkage analysis in DNA from 47 affected and 7 normal individuals. Marker D7S550, located at 7q36, yielded a maximum LOD score of 11.31 at theta = 0.00. Additional markers in the region also showed no recombination. These data indicate that the gene responsible for the hand abnormality in pedigree UR002 maps to the same region as that in previous pedigrees with similar phenotype. Further analyses of recombinants among all the linked families by using new polymorphic markers will narrow the critical genomic region and facilitate positional cloning of the elusive gene.     

Conjugation of classic Bowman-Birk soy inhibitor with a copolymer of ethylene oxide and propylene oxide

A classical soybean inhibitor of the Bowman-Birk type (BBI) with a copolymer of ethylene oxide and propylene oxide (PE) has been synthesized. The BBI-PE conjugate contain five covalently bound polymeric chains per one protein molecule and retains its capacity to inhibit trypsin (Ki = 10(-10) M), alpha-chymotrypsin (Ki = 7 x 10(-8) M) and human granulocyte elastase (Ki = 3 x 10(-8) M). The preservation of the antiproteinase activity in the antichymotrypsin center creates a prerequisite for the manifestation of the anticarcinogenic effect of the inhibitor.     

Tempora mutantur, nos et mutamur in illis!

In March 1992, KAP investigation and HIV blood test were carried out for 860 drug users and 82 spouses in Ruili, Luxi, Longchuan of Yunnan Province, China. The results show that there were 285 IDUs (33.1%) among 860 drug users. Among 282 blood samples of IDUs, the HIV infection rate was 49.0%, highest in Ruili (81.8%, 63/77), then Longchuan (44.6%, 77/166), lowest in Luxi County (5.1%, 2/36). Twelve new HIV+ were found from 75 persons, who had been tested as HIV- in recent two years. Sixty-two blood samples were collected among 82 spouses of IDUs with HIV+, 6 were HIV+ (9.8%), with an increase of 6.7% comparing with results of the investigation two-years ago (3.1%, 2/64).     

High-Temperature Rotational Transitions of Water in Sunspot and Laboratory Spectra

Assignments are presented for spectra of hot water obtained in absorption in sunspots (T approximately 3000°C and 750 相似文献   

Ganglioside GM1 protects cAMP 3'5':phosphodiesterase from inactivation caused by lipid peroxidation in brain synaptosomes of rats

The preincubation of synaptosomes with nanomolar concentrations of ganglioside GM1 was shown to protect Ca(2+)-dependent and Ca(2+)-independent cyclic nucleotide phosphodiesterase from inactivation caused by lipid peroxidation (LPO) induction. Thus, Ca(2+)-dependent phosphodiesterase activity decreased to approximately 34% of the initial value following 30 min of LPO induction, but it constituted more than 60% of the control activity if synaptosomes were preincubated with 10(-8)M GM1, the difference being statistically significant. 10(-6)M alpha-tocopherol had a similar effect. As far as the lipid matrix is concerned, gangliosides were found to prevent to a great extent malonic dialdehyde (MDA) accumulation and to protect polyenoic fatty acids from oxidative destruction. The ability of gangliosides to protect phosphodiesterase from inactivation caused by LPO induction appears to be owing not only to the inhibition of the accumulation of LPO products, but to the direct activation of the enzyme as well, 10(-7) M of ganglioside GM1 having the maximal activating effect. In contrast to alpha-tocopherol and other antioxidants reacting directly with free radicals, the inhibitory effect of gangliosides appears to be mediated by signal transduction systems.     

Aiding troubled employees: the prevalence, cost, and characteristics of employee assistance programs in the United States

Bilirubin neurotoxicity can be mediated by numerous mechanisms due to its increased permeability in neuronal membranes. The present study tests the hypothesis that a prolonged bilirubin infusion modifies the N-methyl-D-aspartate (NMDA) receptor/ ion channel complex in the cerebral cortex of newborn piglets. Studies were performed in seven control and six bilirubin-exposed piglets, 2-4 d of age. Piglets in the bilirubin group received a 35 mg/kg bolus of bilirubin followed by a 4-h infusion (25 mg/kg/h) of a buffer solution containing 0.1 N NaOH, 5% human albumin, and 0.055 Na2HPO4 with 3 mg/mL bilirubin. The final mean bilirubin concentration in the bilirubin group was 495.9 +/- 85.5 mumol/L (29.0 +/- 5.0 mg/dL). The control group received a bilirubin-free buffer solution. Sulfisoxazole was administered to animals in both groups. P2 membrane fractions were prepared from the cerebral cortex. [3H]MK-801 binding assays were performed to study NMDA receptor modification. The Bmax in the control and bilirubin groups were 1.20 +/- 0.10 (mean +/- SD) and 1.32 +/- 0.14 pmol/mg protein, respectively. The value for Kd in the control brains was 6.97 +/- 0.80 nM compared with 4.80 +/- 0.28 nM in the bilirubin-exposed brains (p < 0.001). [3H]Glutamate binding studies did not show a significant difference in the Bmax and Kd for the NMDA-specific glutamate site in the two groups. The results show that in vivo exposure to bilirubin increases the affinity of the receptor (decreased Kd) for [3H]MK-801, indicating that bilirubin modifies the function of the NMDA receptor/ion channel complex in the brain of the newborn piglet. We speculate that the affinity of bilirubin for neuronal membranes leads to bilirubin-mediated neurotoxicity, resulting in either short- or long-term disruption of neuronal function.