Diazoxide attenuates autoimmune encephalomyelitis and modulates lymphocyte proliferation and dendritic cell functionality

Activation of mitochondrial ATP-sensitive potassium (KATP) channels is postulated as an effective mechanism to confer cardio and neuroprotection, especially in situations associated to oxidative stress. Pharmacological activation of these channels inhibits glia-mediated neuroinflammation. In this way, diazoxide, an old-known mitochondrial KATP channel opener, has been proposed as an effective and safe treatment for different neurodegenerative diseases, demonstrating efficacy in different animal models, including the experimental autoimmune encephalomyelitis (EAE), an animal model for Multiple Sclerosis. Although neuroprotection and modulation of glial reactivity could alone explain the positive effects of diazoxide administration in EAE mice, little is known of its effects on the immune system and the autoimmune reaction that triggers the EAE pathology. The aim of the present work was to study the effects of diazoxide in autoimmune key processes related with EAE, such as antigen presentation and lymphocyte activation and proliferation. Results show that, although diazoxide treatment inhibited in vitro and ex-vivo lymphocyte proliferation from whole splenocytes it had no effect in isolated CD4(+) T cells. In any case, treatment had no impact in lymphocyte activation. Diazoxide can also slightly decrease CD83, CD80, CD86 and major histocompatibility complex class II expression in cultured dendritic cells, demonstrating a possible role in modulating antigen presentation. Taken together, our results indicate that diazoxide treatment attenuates autoimmune encephalomyelitis pathology without immunosuppressive effect

Effects of climate and land-use changes on fish catches across lakes at a global scale

Globally, our knowledge on lake fisheries is still limited despite their importance to food security and livelihoods. Here we show that fish catches can respond either positively or negatively to climate and land-use changes, by analyzing time-series data (1970–2014) for 31 lakes across five continents. We find that effects of a climate or land-use driver (e.g., air temperature) on lake environment could be relatively consistent in directions, but consequential changes in a lake-environmental factor (e.g., water temperature) could result in either increases or decreases in fish catch in a given lake. A subsequent correlation analysis indicates that reductions in fish catch was less likely to occur in response to potential climate and land-use changes if a lake is located in a region with greater access to clean water. This finding suggests that adequate investments for water-quality protection and water-use efficiency can provide additional benefits to lake fisheries and food security

Does size matter for horny beetles? A geometric morphometric analysis of interspecific and intersexual size and shape variation in Colophon haughtoni Barnard, 1929, and C. kawaii Mizukami, 1997 (Coleoptera: Lucanidae)

Colophon is an understudied, rare and endangered stag beetle genus with all species endemic to isolated mountain peaks in South Africa’s Western Cape. Geometric morphometrics was used to analyse intersexual and interspecific variation of size and shape in the mandibles, heads, pronota and elytra of two sympatric species: Colophon haughtoni and Colophon kawaii. All measured structures showed significant sexual dimorphism, which may result from male-male competition for females. Female mandibles were too small and featureless for analysis, but male Colophon beetles possess large, ornate mandibles for fighting. Males had significantly larger heads and pronota that demonstrated shape changes which may relate to resource diversion to the mandibles and their supporting structures. Females are indistinguishable across species, but males were accurately identified using mandibles, heads and pronota. Male C. kawaii were significantly larger than C. haughtoni for all structures. These results support the species status of C. kawaii, which is currently in doubt due to its hybridisation with C. haughtoni. We also demonstrate the value of geometric morphometrics as a tool which may aid Colophon conservation by providing biological and phylogenetic insights and enabling species identification

Cervical epithelial damage promotes Ureaplasma parvum ascending infection, intrauterine inflammation and preterm birth induction in mice

Around 40% of preterm births are attributed to ascending intrauterine infection, and Ureaplasma parvum (UP) is commonly isolated in these cases. Here we present a mouse model of ascending UP infection that resembles human disease, using vaginal inoculation combined with mild cervical injury induced by a common spermicide (Nonoxynol-9, as a surrogate for any mechanism of cervical epithelial damage). We measure bacterial load in a non-invasive manner using a luciferase-expressing UP strain, and post-mortem by qPCR and bacterial titration. Cervical exposure to Nonoxynol-9, 24 h pre-inoculation, facilitates intrauterine UP infection, upregulates pro-inflammatory cytokines, and increases preterm birth rates from 13 to 28%. Our results highlight the crucial role of the cervical epithelium as a barrier against ascending infection. In addition, we expect the mouse model will facilitate further research on the potential links between UP infection and preterm birth

From insect to man: Photorhabdus sheds light on the emergence of human pathogenicity

Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway

Incidence and antibiotic susceptibility of genital mycoplasmas in sexually active individuals in Hungary

The aim of this study was to examine the incidence and antibiotic sensitivity of Ureaplasma urealyticum and Mycoplasma hominis strains cultured from the genital discharges of sexually active individuals who attended our STD outpatient service. Samples were taken with universal swab (Biolab®, Budapest, Hungary) into the Urea-Myco DUO kit (Bio-Rad®, Budapest, Hungary) and incubated in ambient air for 48 h at 37 °C. The determination of antibiotic sensitivity was performed in U9 and arginin broth using the SIR Mycoplasma kit (Bio-Rad®, Budapest, Hungary) under the same conditions. Between 01.05.2008 and 31.12.2011, 373/4,466 (8.35 %) genito-urethral samples with U. urealyticum and 41/4,466 (0.91 %) genito-urethral samples with M. hominis infection were diagnosed in sexually active individuals in the National STD Center, Semmelweis University. U. urealyticum was isolated in 12.54 % in the cervix and 4.1 % in the male urethra, while M. hominis was isolated in 1.33 % in the cervix and 0.51 % in the male urethra. The affected age group was between 21 and 60 years old. U. urealyticum strains were sensitive to tetracycline (95.9 %), doxycycline (97.32 %), and azithromycin (85.79 %), and resistant to erythromycin (81.23 %), clindamycin (75.06 %), and ofloxacin (25.2 %). Cross-resistance occurred in 38.71 % of patients to erythromycin and clindamycin. M. hominis strains were sensitive to clindamycin, ofloxacin, and doxycycline in more than 95 %, to tetracycline in 82.92 %, and no cross-resistance was detected among the antibiotics. Our study confirms that the continuously changing antibiotic resistance of ureaplasmas and mycoplasmas should be followed at least in a few centers in every country, so as to determine the best local therapy options for sexually transmitted infection (STI) patients. © 2013 Springer-Verlag Berlin Heidelberg