Animal somatic cell DNA is characterized by a bimodal pattern of methylation: tissue-specific genes are methylated in most cell types whereas housekeeping genes have 5' CpG islands which are constitutively unmethylated. Because methyl moieties derived from the gametes are erased in the morula and early blastula, this profile must be re-established in every generation; this is apparently accomplished by a wave of non-CpG island de novo methylation that occurs at implantation. Using transfection into embryonic stem cells and transgenic mice as a model system, we now show that Sp1 elements play a key role in protecting a CpG island in the adenine phosphoribosyltransferase (APRT) gene from de novo methylation. This recognition mechanism represents a critical step in embryogenesis, as it is responsible for setting up the correct genome methylation pattern which, in turn, is involved in regulating basal gene expression in the organism.

Clinical isolates of Klebsiella pneumoniae and Enterobacter spp. collected from 1990 through 2005 at a tertiary care center were studied for qnr genes. Isolates bearing these genes emerged in the mid-1990s, coinciding with the time of a rapid increase in fluoroquinolone resistance. Sixty percent of these isolates were ciprofloxacin susceptible by CLSI breakpoints.Plasmid-mediated qnr genes confer low-level quinolone resistance that is below the Clinical and Laboratory Standards Institute (CLSI) nonsusceptibility breakpoint but substantial enough to facilitate the selection of chromosomal mutations that confer higher-level resistance (4, 5). qnr has therefore been hypothesized to be a potential contributor to the increase in the prevalence of quinolone resistance among gram-negative bacteria. Epidemiological surveys have found qnrA, qnrB, and qnrS in various Enterobacteriaceae (9). These surveys generally have been performed with outbreak strains or isolates collected over a short period. Hence, little is known about the epidemiological patterns of these genes in a general clinical population over time. We therefore surveyed bloodstream isolates of Enterobacter spp. and Klebsiella pneumoniae collected over a 16-year period for qnr genes in order to more broadly characterize the epidemiology of these resistance elements in a clinical population.(This work was presented in part at the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, 2006.) Methods. All patient-unique bloodstream isolates had been prospectively collected at Hadassah Ein-Kerem Hospital, Jerusalem, since 1990 and kept at Ϫ70°C. For this study, we used Enterobacter spp., including Enterobacter cloacae and Enterobacter aerogenes, and K. pneumoniae and screened all available isolates from selected years from 1990 through 2005. Our selection strategy was to test all isolates from the first year for which all isolates were available (1990 for Enterobacter spp. and 1991 for K. pneumoniae) until the first year that qnr genes were detected. This allowed an accurate determination of the time at which qnr emerged in these populations. The qnr prevalence after emergence was determined by testing all isolates from selected subsequent years; these years were chosen based on convenience and complete isolate availability. All tested isolates were included in the final analysis. For E. cloacae, the following years were chosen:

No abstract

Familial dysautonomia (FD) is an autosomal recessive disorder characterized by developmental arrest in the sensory and autonomic nervous systems and by Ashkenazi Jewish ancestry. We previously had mapped the defective gene (DYS) to an 11-cM segment of chromosome 9q31-33, flanked by D9S53 and D9S105. By using 11 new polymorphic loci, we now have narrowed the location of DYS to <0.5 cM between the markers 43B1GAGT and 157A3. Two markers in this interval, 164D1 and D9S1677, show no recombination with the disease. Haplotype analysis confirmed this candidate region and revealed a major haplotype shared by 435 of 441 FD chromosomes, indicating a striking founder effect. Three other haplotypes, found on the remaining 6 FD chromosomes, might represent independent mutations. The frequency of the major FD haplotype in the Ashkenazim (5 in 324 control chromosomes) was consistent with the estimated DYS carrier frequency of 1 in 32, and none of the four haplotypes associated with FD was observed on 492 non-FD chromosomes from obligatory carriers. It is now possible to provide accurate genetic testing both for families with FD and for carriers, on the basis of close flanking markers and the capacity to identify >98% of FD chromosomes by their haplotype.

A single CRKP clone ST512 has spread efficiently in our region. In this clone, aac(6')-Ib, common in CRKP strains, is carried on a different plasmid from bla(KPC-3).

Contaminated lubricant gel was the cause of this outbreak. The practice of repeatedly refilling gel containers with nonsterile gel was replaced by the use of individual sterile gel sachets in each patient. No further cases occurred. During an invasive procedure involving a sterile body site, such as transrectal ultrasound guided prostate biopsy, using sterile gel is essential. Our experience emphasizes the crucial need to review all invasive procedures from an infection control perspective.

Fusobacterium infections in children can cause a diverse spectrum of disease and is associated with high rates of abscess formation and intracranial complications. Although Fusobacterium nucleatum is abundant in the oral cavity, F. necrophorum is the main pathogen that causes severe infections in healthy children.

We previously showed that the colorectal cancer colonizing bacterium Fusobacterium nucleatum protects tumors from immune cell attack via binding of the fusbacterial Fap2 outer-membrane protein to TIGIT, a checkpoint inhibitory receptor expressed on T cells and NK cells. Helicobacter pylori, the causative agent for peptic ulcer disease, is associated with the development of gastric adenocarcinoma and MALT lymphoma. The HopQ outer-membrane adhesin of H. pylori was recently shown to bind carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) including CEACAM1, an inhibitory receptor expressed mainly by activated T and NK cells. Here we investigated the possibility that similar to Fap2, HopQ can also inhibit immune cell activities by interacting with CEACAM1. We used several approaches to confirm that HopQ indeed interacts with CEACAM1, and show that CEACAM1-mediated activation by HopQ, may inhibit NK and T cell functions.