An insight into the sialome of Simulium guianense (DIPTERA:SIMulIIDAE), the main vector of River Blindness Disease in Brazil

<p>Abstract</p> <p>Background</p> <p>Little is known about the composition and function of the saliva in black flies such as <it>Simulium guianense</it>, the main vector of river blindness disease in Brazil. The complex salivary potion of hematophagous arthropods counteracts their host's hemostasis, inflammation, and immunity.</p> <p>Results</p> <p>Transcriptome analysis revealed ubiquitous salivary protein families--such as the Antigen-5, Yellow, Kunitz domain, and serine proteases--in the <it>S. guianense </it>sialotranscriptome. Insect-specific families were also found. About 63.4% of all secreted products revealed protein families found only in <it>Simulium</it>. Additionally, we found a novel peptide similar to kunitoxin with a structure distantly related to serine protease inhibitors. This study revealed a relative increase of transcripts of the SVEP protein family when compared with <it>Simulium vittatum </it>and <it>S. nigrimanum </it>sialotranscriptomes. We were able to extract coding sequences from 164 proteins associated with blood and sugar feeding, the majority of which were confirmed by proteome analysis.</p> <p>Conclusions</p> <p>Our results contribute to understanding the role of <it>Simulium </it>saliva in transmission of <it>Onchocerca volvulus </it>and evolution of salivary proteins in black flies. It also consists of a platform for mining novel anti-hemostatic compounds, vaccine candidates against filariasis, and immuno-epidemiologic markers of vector exposure.</p

Synthetic lethal targeting of oncogenic transcription factors in acute leukemia by PARP inhibitors

Acute myeloid leukemia (AML) is mostly driven by oncogenic transcription factors, which have been classically viewed as intractable targets using small molecule inhibitor approaches. Here, we demonstrate that AML driven by repressive transcription factors including AML1-ETO and PML-RARα are extremely sensitive to Poly (ADP-ribose) Polymerase (PARP) inhibitor (PARPi), in part due to their suppressed expression of key homologous recombination genes and thus compromised DNA damage response (DDR). In contrast, leukemia driven by MLL fusions with dominant transactivation ability is proficient in DDR and insensitive to PARP inhibition. Intriguing, depletion of an MLL downstream target, Hoxa9 that activates expression of various HR genes, impairs DDR and sensitizes MLL leukemia to PARPi. Conversely, Hoxa9 over-expression confers PARPi resistance to AML1-ETO and PML-RARα transformed cells. Together, these studies describe a potential utility of PARPi-induced synthetic lethality for leukemia treatment and reveal a novel molecular mechanism governing PARPi sensitivity in AML

BpsR Modulates Bordetella Biofilm Formation by Negatively Regulating the Expression of the Bps Polysaccharide

Bordetella bacteria are Gram-negative respiratory pathogens of animals, birds, and humans. A hallmark feature of some Bordetella species is their ability to efficiently survive in the respiratory tract even after vaccination. Bordetella bronchiseptica and Bordetella pertussis form biofilms on abiotic surfaces and in the mouse respiratory tract. The Bps exopolysaccharide is one of the critical determinants for biofilm formation and the survival of Bordetella in the murine respiratory tract. In order to gain a better understanding of regulation of biofilm formation, we sought to study the mechanism by which Bps expression is controlled in Bordetella. Expression of bpsABCD (bpsA-D) is elevated in biofilms compared with levels in planktonically grown cells. We found that bpsA-D is expressed independently of BvgAS. Subsequently, we identified an open reading frame (ORF), BB1771 (designated here bpsR), that is located upstream of and in the opposite orientation to the bpsA-D locus. BpsR is homologous to the MarR family of transcriptional regulators. Measurement of bpsA and bpsD transcripts and the Bps polysaccharide levels from the wild-type and the ΔbpsR strains suggested that BpsR functions as a repressor. Consistent with enhanced production of Bps, the bpsR mutant displayed considerably more structured biofilms. We mapped the bpsA-D promoter region and showed that purified BpsR protein specifically bound to the bpsA-D promoter. Our results provide mechanistic insights into the regulatory strategy employed by Bordetella for control of the production of the Bps polysaccharide and biofilm formation

Surgical site infections following colorectal cancer surgery: a randomized prospective trial comparing common and advanced antimicrobial dressing containing ionic silver

<p>Abstract</p> <p>Background</p> <p>An antimicrobial dressing containing ionic silver was found effective in reducing surgical-site infection in a preliminary study of colorectal cancer elective surgery. We decided to test this finding in a randomized, double-blind trial.</p> <p>Methods</p> <p>Adults undergoing elective colorectal cancer surgery at two university-affiliated hospitals were randomly assigned to have the surgical incision dressed with Aquacel® Ag Hydrofiber dressing or a common dressing. To blind the patient and the nursing and medical staff to the nature of the dressing used, scrub nurses covered Aquacel® Ag Hydrofiber with a common wound dressing in the experimental arm, whereas a double common dressing was applied to patients of control group. The primary end-point of the study was the occurrence of any surgical-site infection within 30 days of surgery.</p> <p>Results</p> <p>A total of 112 patients (58 in the experimental arm and 54 in the control group) qualified for primary end-point analysis. The characteristics of the patient population and their surgical procedures were similar. The overall rate of surgical-site infection was lower in the experimental group (11.1% center 1, 17.5% center 2; overall 15.5%) than in controls (14.3% center 1, 24.2% center 2, overall 20.4%), but the observed difference was not statistically significant (<it>P</it> = 0.451), even with respect to surgical-site infection grade 1 (superficial) versus grades 2 and 3, or grade 1 and 2 versus grade 3.</p> <p>Conclusions</p> <p>This randomized trial did not confirm a statistically significant superiority of Aquacel® Ag Hydrofiber dressing in reducing surgical-site infection after elective colorectal cancer surgery.</p> <p>Trial registration</p> <p>Clinicaltrials.gov: NCT00981110</p