Characteristics of enterobacteria isolated from patients with urogenital pathology

Species composition and a number of persistence characteristics enterobacteria isolated from urine of 42 pregnant and 22 nonpregnant women with pyelonephritis (relapse, remission), from prostatic fluid of 225 males and secretions of cervical canal of 124 women with urogenital pathology (prostatitis, salpingo-oophoritis) were studied. The study revealed that enterobacteria, including Escherichia coli, prevailed in the structure of uromicroflora (66.7-83.3%) and constituted a relatively small proportion among "genital" isolates of microorganisms (19.9-22.2%). Male and female sterility and the presence of enterobacteria in the reproductive tract of patients were found to be directly correlated. Clinical isolates of enterobacteria were shown to possess pronounced seroresistance and the complex of persistence characteristics, including antilysozyme, anti-intercidal and anticomplementary activity.     

Ecovariant differences of Escherichia coli strains with respect to colicinogenicity and colicin resistance

The analysis of 173 Escherichia coli strains, isolated from different sources, for colicinogenicity and colicin resistance revealed that frequency of these signs increased in the following order: water in open reservoirs, intestine, extraintestinal localizations. In most cases resistance to 5 or more bacterial colicins was due to the absence of the corresponding receptors to colicins. Colicin resistance and colicinogenicity render E. coli selective advantages under the conditions of intestinal microbiocenosis.     

The in-vitro effect of the leukocytic cationic protein preparation Intercide on Escherichia coli]

Intercide is a cationic protein with the molecular weight of 11.0-11.5 kD from human leukocytes. The in vitro effect of its different concentrations (0.6 to 1.8 mg/ml) on populations of Escherichia coli M17 and K12 and 120 E.coli isolates from various sources such as water, feces of healthy humans and patients with extraintestinal escherichiosis was studied. The experiments with the bacterial suspensions and broth cultures demonstrated that Intercide had an antibacterial action on both the stationary and growing cells. However, some strains of E.coli were resistant to the lethal effect of Intercide. It was observed for the first time that in a concentration of 1.8 mg/ml Intercide was able to stimulate the biomass growth of some E.coli strains in broth culture. The factor analysis showed that the Intercide stimulating effect was more often evident with respect to extraintestinal escherichiosis pathogens with high anti-Intercide and antilysozyme activities.     

Localization in the cell of the protein forming ATP-dependent potassium-selective channels in a bilayer lipid membrane. An ultrastructural study

The localization in cell of the protein forming in BLM the ATP-dependent potassium-selective channels was studied. The electron-microscopic investigation of rat liver and heart tissue sections after their incubation with Abs against the studied protein and visualization of the protein with secondary Abs conjugated with colloid gold were carried out. The colloid gold particles were observed both in mitochondrial membranes and in membranes of endoplasmic and sarcoplasmic reticulum. In heart mitochondria these particles were significantly greater then in liver mitochondria. The detection of the channel-protein localization both in mitochondria and reticulum, as well as structural similarity between the mitochondrial channel and the precursor of calreticulin suggests that the channel protein belongs to the calreticulin family. The possible function of the studied protein as a channel subunit of the mitochondrial ATP-dependent potassium channel is discussed.     

HK022 bacteriophage Integrase mediated RMCE as a potential tool for human gene therapy

HK022 coliphage site-specific recombinase Integrase (Int) can catalyze integrative site-specific recombination and recombinase-mediated cassette exchange (RMCE) reactions in mammalian cell cultures. Owing to the promiscuity of the 7 bp overlap sequence in its att sites, active ‘attB’ sites flanking human deleterious mutations were previously identified that may serve as substrates for RMCE reactions for future potential gene therapy. However, the wild type Int proved inefficient in catalyzing such RMCE reactions. To address this low efficiency, variants of Int were constructed and examined by integrative site-specific recombination and RMCE assays in human cells using native ‘attB’ sites. As a proof of concept, various Int derivatives have demonstrated successful RMCE reactions using a pair of native ‘attB’ sites that were inserted as a substrate into the human genome. Moreover, successful RMCE reactions were demonstrated in native locations of the human CTNS and DMD genes whose mutations are responsible for Cystinosis and Duchene Muscular Dystrophy diseases, respectively. This work provides a steppingstone for potential downstream therapeutic applications.     

An Examination of the Association between 5-HTTLPR,Combat Exposure,and PTSD Diagnosis among U.S. Veterans

Objective

To examine the association between the 5-HTTLPR polymorphism of the serotonin transporter (SLC6A4) gene, combat exposure, and posttraumatic stress disorder (PTSD) diagnosis and among two samples of combat-exposed veterans.

Method

The first sample included 550 non-Hispanic Black (NHB) combat-exposed veterans. The second sample included 555 non-Hispanic White (NHW) combat-exposed veterans. Participants were genotyped for the 5-HTTLPR/rs25531 variants of the SLC6A4 gene. A structured clinical interview was used to diagnose PTSD. Combat and civilian trauma exposure were assessed with validated self-report instruments. Logistic regression was used to test for main effects of 5-HTTLPR on PTSD diagnosis as well as gene x environment (GxE) interactions after adjusting for sex, ancestry proportion scores, civilian trauma exposure, and combat exposure.

Results

Within the NHB sample, a significant additive effect was observed for 5-HTTLPR (OR = 1.502, p = .0025), such that the odds of having a current diagnosis of PTSD increased by 1.502 for each additional S’ allele. No evidence for an association between 5-HTTLPR and PTSD was observed in the NHW sample. In addition, no evidence for combat x 5-HTTLPR effects were observed in either sample.

Conclusion

The present study suggests that there may be an association between 5-HTTLPR genotype and PTSD diagnosis among NHB veterans; however, no evidence for the hypothesized 5-HTTLPR x combat interaction was found.     

Vasopressin needs an audience: neuropeptide elicited stress responses are contingent upon perceived social evaluative threats

The nonapeptide arginine vasopressin (AVP) plays an important role in hypothalamus-pituitary-adrenal axis regulation and also functions as a social hormone in a wide variety of species, from voles to humans. In the current report we use a variety of stress inducing tasks, including the Trier Social Stress Test (TSST) and intranasal administration of AVP to show that intranasal administration of this neuropeptide leads to a significant increase in salivary cortisol and pulse rate, specifically in conditions where subjects perform tasks in the presence of a social evaluative threat (task performance could be negatively judged by others). In contrast, in conditions without a social evaluative threat (no task condition, modified TSST without audience and bike ergometry), subjects receiving AVP did not differ from subjects receiving placebo. Thus exogenous AVP's influence is contingent upon a circumscribed set of initial conditions that constitute a direct threat to the maintenance of our social selves. Stress evoked by social threat is an integral part of social life and is related to self-esteem and in extreme forms, to poor mental health (e.g., social phobia). Our findings suggest that AVP is a key component in the circuit that interlaces stress and social threat and findings offer inroads to our understanding of individual differences in sociability and in stress response elicited in threatening social situations.     

Spatial phosphoprotein profiling reveals a compartmentalized extracellular signal-regulated kinase switch governing neurite growth and retraction

Brain development and spinal cord regeneration require neurite sprouting and growth cone navigation in response to extension and collapsing factors present in the extracellular environment. These external guidance cues control neurite growth cone extension and retraction processes through intracellular protein phosphorylation of numerous cytoskeletal, adhesion, and polarity complex signaling proteins. However, the complex kinase/substrate signaling networks that mediate neuritogenesis have not been investigated. Here, we compare the neurite phosphoproteome under growth and retraction conditions using neurite purification methodology combined with mass spectrometry. More than 4000 non-redundant phosphorylation sites from 1883 proteins have been annotated and mapped to signaling pathways that control kinase/phosphatase networks, cytoskeleton remodeling, and axon/dendrite specification. Comprehensive informatics and functional studies revealed a compartmentalized ERK activation/deactivation cytoskeletal switch that governs neurite growth and retraction, respectively. Our findings provide the first system-wide analysis of the phosphoprotein signaling networks that enable neurite growth and retraction and reveal an important molecular switch that governs neuritogenesis.