Chemically synthesized zinc finger molecules as nano-addressable probes for double-stranded DNAs

Our experiments describe an alternative method of dsDNA recognition using zinc finger (ZF) molecules which bind DNA specifically and with high affinity. Our aim was to develop zinc finger probes which are able to bind to dsDNA molecules at predetermined sites. In our basic approach we used pairs of complementary oligonucleotides to form dsDNAs, containing one of the three SP1-transcription factor motifs as a zinc finger recognition site. Two zinc finger probes of the SP1 motif were chemically synthesized and modified with a Dy-633 fluorophore. The SP1 peptides were folded into functional zinc fingers using zinc chloride. The addressable dsDNAs were immobilized on optical fibres, and the kinetics and binding rates of the artificial zinc finger probes were measured by a fluorescence detecting device (photomultiplying tube). The two zinc fingers and their corresponding DNA recognition sites served as specific probes and controls for the matching site and vice versa. Our experiments showed that a variety of dsDNA-binding probes may be created by modification of the amino acid sequence of natural zinc finger proteins. Our findings offer an alternative approach of addressing dsDNA molecules, for example for use in a nanoarray device

Cuticular hydrocarbons on old museum specimens of the spiny mason wasp, Odynerus spinipes (Hymenoptera: Vespidae: Eumeninae), shed light on the distribution and on regional frequencies of distinct chemotypes

The mason wasp Odynerus spinipes shows an exceptional case of intrasexual cuticular hydrocarbon (CHC) profile dimorphism. Females of this species display one of two CHC profiles (chemotypes) that differ qualitatively and quantitatively from each other. The ratio of the two chemotypes was previously shown to be close to 1:1 at three sites in Southern Germany, which might not be representative given the Palearctic distribution of the species. To infer the frequency of the two chemotypes across the entire distributional range of the species, we analyzed with GC–MS the CHC profile of 1042 dry-mounted specimens stored in private and museum collections. We complemented our sampling by including 324 samples collected and preserved specifically for studying their CHCs. We were capable of reliably identifying the chemotypes in 91% of drymounted samples, some of which collected almost 200 years ago. We found both chemotypes to occur in the Far East, the presumed glacial refuge of the species, and their frequency to differ considerably between sites and geographic regions. The geographic structure in the chemotype frequencies could be the result of differential selection regimes and/or different dispersal routes during the colonization of the Western Palearctic. The presented data pave the route for disentangling these factors by providing information where to geographically sample O. spinipes for population genetic analyses. They also form the much-needed basis for future studies aiming to understand the evolutionary and geographic origin as well as the genetics of the astounding CHC profile dimorphism that O. spinipes females exhibit

Can J Infect Dis Med Microbiol

Primary muscular echinococcosis is an uncommon localization of hydatid cysts. The nonspecific clinical presentation and possible post-therapeutic complications lead to problems for the diagnosis of this infection and the support of the patient. The authors describe an unusual case of double hydatid cyst of the vastus intermedius muscle. After a precise preoperative evaluation based on clinical, radiological and biological examinations, a surgical excision by pericystectomy combined with perioperative chemotherapy enabled the authors to treat the patient and to prevent postoperative complications. The diagnostic tools and the treatment of this particular type of echinococcosis are discussed. L’échinococcose musculaire primaire est un foyer inhabituel des kystes hydatiques. La présentation clinique non spécifique et les complications post-thérapeutiques éventuelles peuvent s’associer à des difficultés à diagnostiquer cette infection et à soutenir le patient. Les auteurs décrivent un cas inhabituel de double kyste hydatique du muscle vaste intermédiaire. Après une évaluation préopératoire détaillée fondée sur des examens clinique, radiologique et biologique, les auteurs ont traité le patient en procédant à une excision chirurgicale par périkystectomie conjuguée à une chimiothérapie périopératoire, ce qui a permis d’éviter les complications postopératoires. Ils présentent également les outils diagnostiques et le traitement de ce type d’échinococcose

Parasite

A 72-year-old man consulted in November 2012 for abdominal pain in the right upper quadrant. The patient had a history of suspected hepatic amebiasis treated in Senegal in 1985 and has not traveled to endemic areas since 1990. Abdominal CT scan revealed a liver abscess. At first, no parasitological tests were performed and the patient was treated with broad-spectrum antibiotics. Only after failure of this therapy, serology and PCR performed after liver abscess puncture established the diagnosis of hepatic amebiasis. The patient was treated with metronidazole and tiliquinol-tilbroquinol. Amebic liver abscess is the most frequent extra-intestinal manifestation. Hepatic amebiasis 22 years after the last visit to an endemic area is exceptional and raises questions on the mechanisms of latency and recurrence of these intestinal protozoan parasites. Un homme de 72 ans consulte en novembre 2012 pour des douleurs abdominales dans le quadrant supérieur droit. Le patient présente un antécédent probable d’abcès amibien du foie traité en 1985 au Sénégal et n’a pas voyagé en région d’endémie depuis 1990. Le scanner abdominal réalisé met en évidence un abcès hépatique. Dans un premier temps, aucun examen parasitologique n’est effectué et le patient est traité par des antibiotiques à large spectre. Suite à l’échec de ce traitement, la sérologie et la PCR réalisées après ponction de l’abcès hépatique, établissent le diagnostic d’amibiase hépatique. Le patient est traité par métronidazole et tiliquinol-tilbroquinol. L’abcès amibien du foie est la manifestation extra-intestinale de l’amibiase la plus fréquente. L’amibiase hépatique 22 ans après le dernier voyage en zone d’endémie est exceptionnelle et soulève des questions concernant les mécanismes de latence et de récurrence des protozoaires intestinaux

The impact of corporate social responsibility disclosure on financial performance : evidence from the GCC Islamic banking sector.

This paper examines the relationship between corporate social responsibility (CSR) and financial performance for Islamic banks in the Gulf Cooperation Council (GCC) region over the period 2000–2014 by generating CSR-related data through disclosure analysis of the annual reports of the sampled banks. The findings of this study indicate that there is a significant positive relationship between CSR disclosure and the financial performance of Islamic banks in the GCC countries. The results also show a positive relationship between CSR disclosure and the future financial performance of GCC Islamic banks, potentially indicating that current CSR activities carried out by Islamic banks in the GCC could have a long-term impact on their financial performance. Furthermore, despite demonstrating a significant positive relationship between the composite measure of the CSR disclosure index and financial performance, the findings show no statistically significant relationship between the individual dimensions of the CSR disclosure index and the current financial performance measure except for ‘mission and vision’ and ‘products and services’. Similarly, the empirical results detect a positive significant association only between ‘mission and vision’ dimension and future financial performance of the examined banks

NUDT2 Disruption Elevates Diadenosine Tetraphosphate (Ap4A) and Down-Regulates Immune Response and Cancer Promotion Genes.

Regulation of gene expression is one of several roles proposed for the stress-induced nucleotide diadenosine tetraphosphate (Ap4A). We have examined this directly by a comparative RNA-Seq analysis of KBM-7 chronic myelogenous leukemia cells and KBM-7 cells in which the NUDT2 Ap4A hydrolase gene had been disrupted (NuKO cells), causing a 175-fold increase in intracellular Ap4A. 6,288 differentially expressed genes were identified with P < 0.05. Of these, 980 were up-regulated and 705 down-regulated in NuKO cells with a fold-change ≥ 2. Ingenuity® Pathway Analysis (IPA®) was used to assign these genes to known canonical pathways and functional networks. Pathways associated with interferon responses, pattern recognition receptors and inflammation scored highly in the down-regulated set of genes while functions associated with MHC class II antigens were prominent among the up-regulated genes, which otherwise showed little organization into major functional gene sets. Tryptophan catabolism was also strongly down-regulated as were numerous genes known to be involved in tumor promotion in other systems, with roles in the epithelial-mesenchymal transition, proliferation, invasion and metastasis. Conversely, some pro-apoptotic genes were up-regulated. Major upstream factors predicted by IPA® for gene down-regulation included NFκB, STAT1/2, IRF3/4 and SP1 but no major factors controlling gene up-regulation were identified. Potential mechanisms for gene regulation mediated by Ap4A and/or NUDT2 disruption include binding of Ap4A to the HINT1 co-repressor, autocrine activation of purinoceptors by Ap4A, chromatin remodeling, effects of NUDT2 loss on transcript stability, and inhibition of ATP-dependent regulatory factors such as protein kinases by Ap4A. Existing evidence favors the last of these as the most probable mechanism. Regardless, our results suggest that the NUDT2 protein could be a novel cancer chemotherapeutic target, with its inhibition potentially exerting strong anti-tumor effects via multiple pathways involving metastasis, invasion, immunosuppression and apoptosis