Carbonic anhydrase inhibitors. Aromatic/heterocyclic sulfonamides incorporating phenacetyl,pyridylacetyl and thienylacetyl tails act as potent inhibitors of human mitochondrial isoforms VA and VB

A series of aromatic/heterocyclic sulfonamides incorporating phenyl(alkyl), halogenosubstituted-phenyl- or 1,3,4-thiadiazole-sulfonamide moieties and thienylacetamido; phenacetamido and pyridinylacetamido tails were prepared and assayed as inhibitors of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic human (h) hCA I and hCA II, and the mitochondrial hCA VA and hCA VB. The new compounds showed moderate inhibition of the two cytosolic isoforms (K_Is of 50–390 nM) and excellent inhibitory activity against the two mitochondrial enzymes, with many low nanomolar inhibitors detected (K_Is in the range of 5.9–10.2 nM). All substitution patterns explored here lead to effective hCA VA/VB inhibitors. Some hCA VA/VB selective inhibitors were also detected, with selectivity ratios for inhibiting the mitochondrial over the cytosolic isozymes of around 55.5–56.9. As hCA VA/VB are involved in several biosynthetic processes catalyzed by pyruvate carboxylase, acetyl CoA carboxylase, and carbamoyl phosphate synthetases I and II, providing the bicarbonate substrate to these carboxylating enzymes involved in fatty acid biosynthesis, their selective inhibition may lead to the development of antiobesity agents possessing a new mechanism of action.     

The interaction of multiple environmental stressors affects adaptation to a novel habitat in the natterjack toad Bufo calamita

The potential to adapt to novel environmental conditions is a key area of interest for evolutionary biology. However, the role of multiple selection pressures on adaptive responses has rarely been investigated in natural populations. In Sweden, the natterjack toad Bufo calamita inhabits two separate distribution areas, one in southernmost Sweden and one on the west coast. We characterized the larval habitat in terms of pond size and salinity in the two areas, and found that the western populations are more affected by both desiccation risk and pond salinity than the southern populations. In a common garden experiment manipulating salinity and temperature, we found that toads from the west coast populations were locally adapted to shorter pond duration as indicated by their higher development and growth rates. However, despite being subjected to higher salinity stress in nature, west coast toads had a poorer performance in saline treatments. We found that survival in the saline treatments in the west coast populations was positively affected by larger body mass and longer larval period. Furthermore, we found negative genetic correlations between body mass and growth rate and their plastic responses to salinity. These results implicate that the occurrence of multiple environmental stressors needs to be accounted for when assessing the adaptive potential of organisms and suggest that genetic correlations may play a role in constraining adaptation of natural populations.     

G-308A TNF-α polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: Case-control study

Background: Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine that may act as an endogenous tumor promoter. A genetic polymorphism of TNF-α gene at position ?308 promoter region is involved in the regulation of expression level and has been found to be associated with susceptibility to various types of cancer. Methods: To determine the association of the TNF-α gene G-308A polymorphism on the risk of hepatocellular carcinoma (HCC) in a Turkish population, a hospital-based case-control study was designed consisting of 110 diagnosis subjects with hepatocellular carcinoma and 110 cancer-free control subjects matched on age, gender, smoking and alcohol status. The genotype frequency of this polymorphism was determined by using a polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay. Results: The distribution G-308A genotype was significantly associated with the risk of HCC (p < 0.001, odds ratio [OR] = 4.75, 95% confidence interval [CI] = 2.25–9.82 for ?308 AA/GA genotypes versus GG genotype). Conclusion: We suggested that the presence of the high producer allele ?308A in the TNF-α gene appears to be associated with an increased risk for the development of HCC in Turkish population.     

Investigation of binding properties of dicationic styrylimidazo[1,2‐a]pyridinium dyes to human serum albumin by spectroscopic techniques

The binding interaction between two dicationic styrylimidazo[1,2‐a]pyridinium dyes and human serum albumin (HSA) was investigated at physiological conditions using fluorescence, UV–vis absorption, and circular dichroism (CD) spectroscopies. Analysis of the fluorescence titration data at different temperatures suggested that the fluorescence quenching mechanism of HSA by these dyes was static. The calculated thermodynamic parameters (ΔG°, ΔH° and ΔS°) indicated that hydrogen bonding and van der Waals forces played a major role in the formation of the dye–HSA complex. Binding distances (r) between dyes and HSA were calculated according to Förster's non‐radiative energy transfer theory. Studies of conformational changes of HSA using CD measurements indicate that the α‐helical content of the protein decreased upon binding of the dyes. Copyright © 2016 John Wiley & Sons, Ltd.     

Determination of some structural features of the nest paper materials of Dolichovespula Saxonica Fabricius, 1793 (Hymenoptera: Vespinae) in Turkey

The purpose of this paper is to identify the nest materials, some physical characteristics and the elemental composition of the nest of Dolichovespula saxonica (Fabricius, 1793). The nest surfaces were observed with a stereomicroscope and scanning electron microscope (SEM). In the inner surface of the D. saxonica nest the medium thickness of the fibers in the envelope and comb varied between 7.14 and 26.9 μm, respectively and averaged 16.4 μm. In the outer surface of the nest the medium thickness of the fibers in the envelope and comb were between 3.52 and 5.70 μm, respectively and averaged 4.63 μm. The nitrogen concentration of the nest of D. saxonica was 0.616% and the amount of protein was 3.08%. The percentages of the fibers, saliva, oil and the water absorption capacity were calculated as 67–70%, 23–30%, 12–18% and 110–140%, respectively. However, the amount of the element Cadmium (Cd) in the nest was found to have a value of 0.2 ppm. The major compounds of wasp nests are plant fibers, saliva and oil. However, the concentrations and ratios of the nest material compounds depend on the plant variety, place of origin, and time of harvest as well as on the processing and saliva conditions. The colors of the nest are beige, cream and grey with long dark brown lines. As a result of our study, we have found that the rates and quantities of physical characteristics, elemental composition and the fibers in the envelope and comb of the nest of D. saxonica change with environmental conditions.     

Phytoplasmas of sesame and Orosius orientalis are genetically diverse based on 16S rDNA sequencing and PCR-RFLP in Turkey

Sesame phyllody causes significant yield losses mainly in Mediterranean region of Turkey. To detect and identify phytoplasmas of sesame and the cicadellid vector Orosius orientalis, samples were collected during 2011–2013 in Antalya. Nested PCR amplification of the 16S rDNA gave an amplification band of approximately 1246 bp corresponding to the 16Sr F2nR2 region. Identification of the phytoplasmas based on sequence homology revealed presence of the 16Sr groups II (Peanut witches’-broom, PnWB), VI (Clover proliferation, CP) and IX (Pigeon pea witches’-broom, PPWB) in sesame plants. PnWB and CP were detected in O. orientalis. Subgroups were determined by sequencing and PCR-RFLP of the F2nR2 region. 16Sr subgroups II-D, VI-A and IX-C were identified from sesame and II-D and VI-A subgroups from the insect vector. This study shows that phytoplasmas in sesame and O. orientalis are genetically diverse and to the knowledge, VI-A group phytoplasmas from sesame and O. orientalis were characterised molecularly for the first time in Turkey.