Decoy peptides that bind dynorphin noncovalently prevent NMDA receptor-mediated neurotoxicity

Prodynorphin-derived peptides elicit various pathological effects including neurological dysfunction and cell death. These actions are reduced by N-methyl-d-aspartate receptor (NMDAR) but not opioid receptor antagonists suggesting NMDAR-mediation. Here, we show that a conserved epitope (KVNSEEEEEDA) of the NR1 subunit of the NMDAR binds dynorphin peptides (DYNp) noncovalently. Synthetic peptides containing this epitope form stable complexes with DYNp and prevent the potentiation of NMDAR-gated currents produced by DYNp. They attenuate DYNp-evoked cell death in spinal cord and prevent, as well as reverse, DYNp-induced paralysis and allodynia. The data reveal a novel mechanism whereby prodynorphin-derived peptides facilitate NMDAR function and produce neurotoxicity. Furthermore, they suggest that synthetic peptides that bind DYNp, thus preventing their interaction with NMDAR, may be novel therapeutic agents for the treatment of spinal cord injury.     

Fine haplotype structure of a chromosome 17 region in the laboratory and wild mouse

Extensive linkage disequilibrium among classical laboratory strains represents an obstacle in the high-resolution haplotype mapping of mouse quantitative trait loci (QTL). To determine the potential of wild-derived mouse strains for fine QTL mapping, we constructed a haplotype map of a 250-kb region of the t-complex on chromosome 17 containing the Hybrid sterility 1 (Hst1) gene. We resequenced 33 loci from up to 80 chromosomes of five mouse (sub)species. Trans-species single-nucleotide polymorphisms (SNPs) were rare between Mus m. musculus (Mmmu) and Mus m. domesticus (Mmd). The haplotypes in Mmmu and Mmd differed and therefore strains from these subspecies should not be combined for haplotype-associated mapping. The haplotypes of t-chromosomes differed from all non-t Mmmu and Mmd haplotypes. Half of the SNPs and SN indels but only one of seven longer rearrangements found in classical laboratory strains were useful for haplotype mapping in the wild-derived M. m. domesticus. The largest Mmd haplotype block contained three genes of a highly conserved synteny. The lengths of the haplotype blocks deduced from 36 domesticus chromosomes were in tens of kilobases, suggesting that the wild-derived Mmd strains are suitable for fine interval-specific mapping.     

Fluid flow induces biofilm formation in Staphylococcus epidermidis polysaccharide intracellular adhesin-positive clinical isolates

Staphylococcus epidermidis is a common cause of catheter-related bloodstream infections, resulting in significant morbidity and mortality and increased hospital costs. The ability to form biofilms plays a crucial role in pathogenesis; however, not all clinical isolates form biofilms under normal in vitro conditions. Strains containing the ica operon can display significant phenotypic variation with respect to polysaccharide intracellular adhesin (PIA)-based biofilm formation, including the induction of biofilms upon environmental stress. Using a parallel microfluidic approach to investigate flow as an environmental signal for S. epidermidis biofilm formation, we demonstrate that fluid shear alone induces PIA-positive biofilms of certain clinical isolates and influences biofilm structure. These findings suggest an important role of the catheter microenvironment, particularly fluid flow, in the establishment of S. epidermidis infections by PIA-dependent biofilm formation.     

Expression of DENDRIN in several glomerular diseases and correlation to pathological parameters and renal failure - preliminary study

Background

In glomerular injury dendrin translocates from the slit diaphragm to the podocyte nucleus, inducing apoptosis. We analyzed dendrin expression in IgA glomerulonephritis and Henoch Schönlein purpura (IgAN/HSP) versus in podocytopathies minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), and compared it to pathohistological findings and renal function at the time of biopsy and the last follow-up.

Methods

Twenty males and 13 females with median of age 35?years (min-max: 3–76) who underwent percutaneous renal biopsy and had diagnosis of glomerular disease (GD) were included in this retrospective study. Fifteen patients had IgAN/HSP and eighteen podocytopathy. Control group consisted of ten patients who underwent nephrectomy due to renal cancer. Dendrin expression pattern (membranous, dual, nuclear or negative), number of dendrin positive nuclei and proportion of dendrin negative glomeruli were analyzed.

Results

In GD and the control group significant differences in number of dendrin positive nuclei and proportion of dendrin negative glomeruli were found (P?=?0.004 and P?=?0.003, respectively). Number of dendrin positive nuclei was higher in podocytopathies than in IgAN/HSP, 3.90 versus 1.67 (P?=?0.028). Proportion of dendrin negative glomeruli correlated to higher rates of interstitial fibrosis (P?=?0.038), tubular atrophy (P?=?0.011) and globally sclerotic glomeruli (P?=?0.008). Dual and nuclear dendrin expression pattern were connected with lower rate of interstitial fibrosis and tubular atrophy than negative dendrin expression pattern (P?=?0.024 and P?=?0.017, respectively). Proportion of dendrin negative glomeruli correlated with lower creatinine clearance (CC) at the time of biopsy and the last follow-up (P?=?0.010 and P?<?0.001, respectively). Dendrin expression pattern correlated to CC at the last follow-up (P?=?0.009), being lower in patients with negative than nuclear or dual dendrin expression (P?=?0.034 and P?=?0.004, respectively).

Conclusion

In this pilot study the number of dendrin positive nuclei was higher in podocytopathies than in inflammatory GD. Negative dendrin expression pattern correlated to chronic tubulointerstitial changes and lower CC, which needs to be confirmed in a larger series.

     

Inhibitory effect of essential oil from <Emphasis Type="Italic">Nepeta rtanjensis</Emphasis> on fungal spore germination

The ability of Nepeta rtanjensis essential oil to inhibit conidia germination of fungi was evaluated in vitro. Tested fungi included in research were Cladosporium cladosporioides, Trichoderma viride and two Alternaria species originally isolated from N. rtanjensis. The conidia of Cladosporium cladosporioides were most susceptible to the N. rtanjensis essential oil treatment, and the oil concentration of 0.1 μg ml⁻¹ caused the maximum of conidia germination inhibition. The highest concentration used in experiment that caused the maximum of conidia germination inhibition was 0.6 μg ml⁻¹ for Alternaria isolated from leaf surface of N. rtanjensis. The germ tube elongation of Alternaria isolates significantly decreased in response of different concentrations of oil used in experiment.     

Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse

Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm) and Mus m. domesticus (Mmd), it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2) genomic locus on Chromosome X (Chr X) by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s) responsible for variation in the global recombination rate between closely related mouse subspecies.     

In vitro inhibition of Helicobacter pylori by micromycetes

The anti-Helicobacter pylori effect of 22 micromycetes were studied against one standard strain and 11 clinical isolates of H. pylori. Penicillium ochlochloron and Penicillium funiculosum have been proven the most active fungi against this microorganism. Further bio-guided chemical analysis of P. funiculosum afforded an active component identified as (-) 2,3,4-trihydroxybutanamide.     

Serum sickness and uveitis

Serum sickness is immune response to a foreign antigen, usually a heterologous protein. Incidence rate is less than 0.5%. Antigens and responding antibodies form circulating immunocomplex that is characteristic for serum sickness. The condition occurs 7-15 days after exposure to the antigen, usually with clinical picture of glomerulonephritis. The immunocomplex circulates to other tissues where it sediments and causes inflammation, such as arteritis, neuritis, synovitis. The aim of this research is to present the break out of serum sickness in form of anterior uveitis due to azithromycin therapy administered by mouth. Identifying of anterior uveitis may help in early diagnostics and treatment of serum sickness.     

Intraocular histiocytosis in a 12-year-old girl without systemic disease

Isolated intraocular histiocytosis is a rare disease that may manifest by recurrent uveitis and solid subretinal masses. The course, diagnosis and treatment of isolated intraocular histiocytosis in a 12-year-old girl are presented. As extensive diagnosis and therapy with corticosteroids and tuberculostatics failed to produce satisfactory results, diagnostic-therapeutic vitrectomy was performed. The intraoperatively obtained material was examined by the methods of histopathology, cytology and immunocytochemistry, along with herpes and cytomegalovirus polymerase chain reaction. The vitreous inflammatory exudate and subretinal masses were operatively removed. Analysis of the intraoperatively obtained material pointed to histiocytosis, whereas additional examinations revealed no systemic manifestations of the disease. Chronic uveitides that respond poorly to classic immunosuppressive therapy require multidisciplinary analysis of intraocular material. Pars plana vitrectomy is an appropriate diagnostic-therapeutic operative procedure.