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.     

Nucleotide sequence of a chicken vitellogenin gene and derived amino acid sequence of the encoded yolk precursor protein

The gene encoding the major vitellogenin from chicken has been completely sequenced and its exon-intron organization has been established. The gene is 20,342 base-pairs long and contains 35 exons with a combined length of 5787 base-pairs. They encode the 1850-amino acid pre-peptide of vitellogenin, which is the precursor of the mature yolk proteins, the serine-rich and heavily phosphorylated phosvitin and the lipovitellin. The 217-amino acid phosvitin polypeptide occupies an internal position (residue 1112 through 1328) within the vitellogenin molecule. The 125,000 and 30,000 Mr lipovitellin polypeptides are encoded by the sequences at the N-terminal and the C-terminal sides of the phosvitin section, respectively. The main features of the gene and protein sequences, and the evolutionary implications, are discussed.     

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.     

Dependence of the intensity of the immune response on the characteristics of the formation of a Salmonella typhi antigen depot on erythrocytes

Experiments on inbred mice, opposite in the capacity of their erythrocytes for the sorption of S. typhi antigens, have revealed that the intensity of immune response to the antigens depends on the functional potency of immunocompetent cells and the conditions of their priming. The optimal manifestations of the conditions for lymphocyte priming depends on the character of the antigen fixation by erythrocytes and antigen supply from the depot into the blood stream.     

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).     

Functional consequences of DECTIN-1 early stop codon polymorphism Y238X in rheumatoid arthritis

Introduction

We have previously demonstrated that ex vivo inhibition of costimulatory molecules on antigen-pulsed dendritic cells (DCs) can be useful for induction of antigen-specific immune deviation and suppression of autoimmune arthritis in the collagen induced arthritis (CIA) model. The current study evaluated a practical method of immune modulation through temporary systemic inhibition of the costimulatory molecule CD40.

Methods

Mice with collagen II (CII)-induced arthritis (CIA) were administered siRNA targeting the CD40 molecule. Therapeutic effects were evaluated by clinical symptoms, histopathology, Ag-specific T cell and B cell immune responses.

Results

Systemic administration of CD40-targeting siRNA can inhibit antigen-specific T cell response to collagen II, as well as prevent pathogenesis of disease in both a pre- and post-immunization manner in the CIA model. Disease amelioration was associated with suppression of Th1 cytokines, attenuation of antibody production, and upregulation of T regulatory cells.

Conclusions

These studies support the feasibility of transient gene silencing at a systemic level as a mechanism of resetting autoreactive immunity.     

Structure of the DNA-bound BRCA1 C-terminal Region from Human Replication Factor C p140 and Model of the Protein-DNA Complex

BRCA1 C-terminal domain (BRCT)-containing proteins are found widely throughout the animal and bacteria kingdoms where they are exclusively involved in cell cycle regulation and DNA metabolism. Whereas most BRCT domains are involved in protein-protein interactions, a small subset has bona fide DNA binding activity. Here, we present the solution structure of the BRCT region of the large subunit of replication factor C bound to DNA and a model of the structure-specific complex with 5′-phosphorylated double-stranded DNA. The replication factor C BRCT domain possesses a large basic patch on one face, which includes residues that are structurally conserved and ligate the phosphate in phosphopeptide binding BRCT domains. An extra α-helix at the N terminus, which is required for DNA binding, inserts into the major groove and makes extensive contacts to the DNA backbone. The model of the protein-DNA complex suggests 5′-phosphate recognition by the BRCT domains of bacterial NAD⁺-dependent ligases and a nonclamp loading role for the replication factor C complex in DNA transactions.     

Identifying potential survival strategies of HIV-1 through virus-host protein interaction networks

Background  

The National Institute of Allergy and Infectious Diseases has launched the HIV-1 Human Protein Interaction Database in an effort to catalogue all published interactions between HIV-1 and human proteins. In order to systematically investigate these interactions functionally and dynamically, we have constructed an HIV-1 human protein interaction network. This network was analyzed for important proteins and processes that are specific for the HIV life-cycle. In order to expose viral strategies, network motif analysis was carried out showing reoccurring patterns in virus-host dynamics.