Phenotypic variability and therapeutic implications of Candida species in patients with oral lichen planus

We investigated the prevalence and phenotypic variation of Candida species in oral lichen planus (OLP) and the therapeutic implications of our findings. Eighty patients with clinically and histopathologically confirmed cases of OLP (64 non-erosive, 16 erosive) and a control group of 80 healthy individuals with no predisposing factors for oral candidiasis were examined for evidence of Candida infection. Oral swabs and smears were obtained for cytology and culture. Identification, speciation and antifungal susceptibility tests of Candida isolates were performed using an automated microbial identification system. Fifty percent of erosive OLP cases, 28% of non-erosive cases and none of the controls showed evidence of Candida. Candida albicans was found predominantly in non-erosive OLP, while other Candida species were predominate in erosive OLP. Non-Candida albicans isolates (C. glabrata, C. krusei) were resistant to the commonly used antifungals, clotrimazole and fluconazole. Candida infection is common in cases of OLP. We recommend antifungal sensitivity testing prior to antifungal therapy for the erosive form of OLP.     

Estrogen-Induced Synthesis of Yolk Proteins in Roosters

Vitellogenin is the serum precursor of the yolk proteins -lipovitellin,rß-lipovitellin, and phosvitin. The precursor canbe dissociated to produce the yolk proteins only by proteolyticenzymatic action, to which it is very susceptible. Denaturationin sodium dodecyl sulfate, combined with reduction of disulfidebridges and blocking of thiols, yields a complex with a molecularweight of 200,000 to 250,000. -Lipovitellin contains three polypeptides,with molecular weights of about 135,000, 105,000, and 40,000,and rß-lipovitellin is composed of two polypeptidechains with molecular weights of 135,000 and 30,000. The 40,000subunit of -lipovitellin and both rß-lipovitellinsubunits are phosphopeptides We tested RNA isolated from the liver of estrogen-treated roostersfor mRNA activity in a cell-free reticulocyte system. The vitellogeninmRNA has a sedimentation coefficient greater than 28S and thuscontains enough information to code for a long polypeptide chain.Estrogen administration to roosters induces the appearance ofvitellogenin and a lowdensity lipoprotein, the syntheses ofwhich are not coordinated. The course of vitellogenin synthesiswas calculated from accumulation and turnover data, and it wasfound that from about 25 hr after estradiol-17rß administrationthe rate of vitellogenin synthesis increases linearly for severaldays, paralleling an increase in vitellogenin-synthesizing polysomes.Thus, we estimate a constant translation rate of about 8 aminoacids per ribosome per sec. A "memory" effect is observed when a second hormone dose isgiven some time after the vitellogenin induced by the firstdose has disappeared from the blood. After the second dose vitellogeninsynthesis is detected sooner, and its initial increase is morerapid, than after the first dose. Although the synthesis ofvitellogenin starts 3 to 4 hr after the second as well as afterthe first injection, the rate of synthesis after the first injectionincreases much more slowly during the first 15 hr than duringthe subsequent period of linear accumulation, whereas afterthe second injection the linear increase in the rate of synthesisbegins immediately after the lag period of 3 to 4 hr. The "memory"effect is undiminished even 50 days after the first hormonedose; thus, the causative factor either is very stable or issynthesized in great excess during the first stimulation. Whenthe second injection is given during the descending part ofthe turnover curve, an increase in vitellogenin synthesis isobserved within 3.5 hr. There are thus at least three different effects of estradiol;(i) the "memory" effect, which probably is due to commitmentor differentiation of vitellogenin-synthesizing cells; (ii)the effect that causes the committed cells to give full responseafter the 3- to 4-hr lag period; and (iii) the effect that causesthe immediate response. To explain these results we suggestthat committed cells can synthesize vitellogenin mRNA only duringa certain period of the cell cycle.     

Specific stimulation of ribosomal RNA synthesis in E. coli by a protein factor

Summary Ribosomal RNA synthesis in a purified system is stimulated by a crude protein fraction prepared from E. coli. The positive effector which is not associated with RNA polymerase, nor is the sigma factor, increases the initiation frequency on a rRNA operon. The additional rRNA synthesis is inhibited by ppGpp to the same extent as the basal one.The evidence presented points to the existence of a positive control element for rRNA synthesis, which activity depends upon the physiological state of the cell.     

Characterization of a polymorphism in the 3′ part of the chicken vitellogenin gene

Summary An allele giving rise to a polymorphism within the 3 part of the chicken vitellogenin gene was cloned, sequenced, and compared to the previously cloned allele. The polymorphism is formed by a perfect copy of 343 bp from intron 32 in tandem array with a perfect copy of 244 bp from intron 33; this 587-bp element is inserted in a head-to-tail arrangement in intron 33. We propose a mechanism in which an unequal crossing-over resulted in a vitellogenin gene with two exons 33, one of which was subsequently deleted. Thus, intron 33 was enlarged by the tandem repeats without affecting the protein-encoding sequence of the gene. At the boundaries of the repeated elements, two short direct repeats are found that resemble the recombination signals of immunoglobulin genes. They may have had a key role in the formation of the new allele.     

The GLUT9 gene is associated with serum uric acid levels in Sardinia and Chianti cohorts

High serum uric acid levels elevate pro-inflammatory–state gout crystal arthropathy and place individuals at high risk for cardiovascular morbidity and mortality. Genome-wide scans in the genetically isolated Sardinian population identified variants associated with serum uric acid levels as a quantitative trait. They mapped within GLUT9, a Chromosome 4 glucose transporter gene predominantly expressed in liver and kidney. SNP rs6855911 showed the strongest association (p = 1.84 × 10⁻¹⁶), along with eight others (p = 7.75 × 10⁻¹⁶ to 6.05 × 10⁻¹¹). Individuals homozygous for the rare allele of rs6855911 (minor allele frequency = 0.26) had 0.6 mg/dl less uric acid than those homozygous for the common allele; the results were replicated in an unrelated cohort from Tuscany. Our results suggest that polymorphisms in GLUT9 could affect glucose metabolism and uric acid synthesis and/or renal reabsorption, influencing serum uric acid levels over a wide range of values.     

The high-resolution NMR structure of the R21A Spc-SH3:P41 complex: Understanding the determinants of binding affinity by comparison with Abl-SH3

Background  

SH3 domains are small protein modules of 60–85 amino acids that bind to short proline-rich sequences with moderate-to-low affinity and specificity. Interactions with SH3 domains play a crucial role in regulation of many cellular processes (some are related to cancer and AIDS) and have thus been interesting targets in drug design. The decapeptide APSYSPPPPP (p41) binds with relatively high affinity to the SH3 domain of the Abl tyrosine kinase (Abl-SH3), while it has a 100 times lower affinity for the α-spectrin SH3 domain (Spc-SH3).     

GENOME: a rapid coalescent-based whole genome simulator

Summary: GENOME proposes a rapid coalescent-based approach tosimulate whole genome data. In addition to features of standardcoalescent simulators, the program allows for recombinationrates to vary along the genome and for flexible population histories.Within small regions, we have evaluated samples simulated byGENOME to verify that GENOME provides the expected LD patternsand frequency spectra. The program can be used to study thesampling properties of any statistic for a whole genome study. Availability: The program and C++ source code are availableonline at http://www.sph.umich.edu/csg/liang/genome/ Contact: lianglim{at}umich.edu Supplementary information: Supplementary data are availableat Bioinformatics online. Associate Editor: Martin Bishop     

A comparison of phasing algorithms for trios and unrelated individuals

Knowledge of haplotype phase is valuable for many analysis methods in the study of disease, population, and evolutionary genetics. Considerable research effort has been devoted to the development of statistical and computational methods that infer haplotype phase from genotype data. Although a substantial number of such methods have been developed, they have focused principally on inference from unrelated individuals, and comparisons between methods have been rather limited. Here, we describe the extension of five leading algorithms for phase inference for handling father-mother-child trios. We performed a comprehensive assessment of the methods applied to both trios and to unrelated individuals, with a focus on genomic-scale problems, using both simulated data and data from the HapMap project. The most accurate algorithm was PHASE (v2.1). For this method, the percentages of genotypes whose phase was incorrectly inferred were 0.12%, 0.05%, and 0.16% for trios from simulated data, HapMap Centre d'Etude du Polymorphisme Humain (CEPH) trios, and HapMap Yoruban trios, respectively, and 5.2% and 5.9% for unrelated individuals in simulated data and the HapMap CEPH data, respectively. The other methods considered in this work had comparable but slightly worse error rates. The error rates for trios are similar to the levels of genotyping error and missing data expected. We thus conclude that all the methods considered will provide highly accurate estimates of haplotypes when applied to trio data sets. Running times differ substantially between methods. Although it is one of the slowest methods, PHASE (v2.1) was used to infer haplotypes for the 1 million-SNP HapMap data set. Finally, we evaluated methods of estimating the value of r(2) between a pair of SNPs and concluded that all methods estimated r(2) well when the estimated value was >or=0.8.