Synthesis,Molecular Modeling,and Biological Evaluation of Novel Chiral Thiosemicarbazone Derivatives as Potent Anticancer Agents

A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF‐7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC‐27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound 17b exhibited the most potent activity (IC₅₀ 4.6 μM) against HGC‐27 as compared with the reference compound, sindaxel (IC₅₀ 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents. Chirality 27:177–188, 2015. © 2014 Wiley Periodicals, Inc.     

A stereological study of the effects of mercury inhalation on the cerebellum

Mercury in the environment that arises from organic and inorganic sources can cause irreversible damage to the nervous system. Toxicity may be direct or may arise from interactions with other metals in the environment. We evaluated the possible effects of mercury vapor on rat cerebellum. Twelve adult female rats were divided into control and experimental groups. The rats in the experimental group were exposed to mercury vapor for 9 h/day for 45 days. Cerebellar tissue samples were evaluated using stereology and for histopathology. The total number of Purkinje cells was estimated using a physical disector method. We found that in the experimental group, overall volume decreased and the number of Purkinje cells was reduced. We also found cellular damage including pycnotic nuclei, eosinophilic cytoplasm and vacuolization; these features were absent in the control group. We found that chronic exposure to inorganic mercury vapor is toxic to the cerebellum.     

Comparison of ITO and ZnO ternary glassy composites in terms of radiation shielding properties by Monte Carlo N-particle transport code and BXCOM

In the present study, radiation shielding properties of two glassy composite materials that are widely used in electronics, photovoltaic applications, and sensor technology, were investigated in the photon energy range from 15 keV to 15 MeV. The materials chosen were (ITO)/V2O5/B2O3 and ZnO/V2O5/B2O3 including various concentrations of B2O3. Radiation interaction was simulated and shielding parameters calculated by means of the MCNP and BXCOM codes. More specifically, buildup factors, effective electron density ($$N_{\text{eff}}$$) and effective atomic number ($$Z_{\text{eff}}$$) were calculated with BXCOM, while mass attenuation coefficients ($$\mu /\rho$$), half-value layer (HVL) and tenth-value layer (TVL) values were calculated with MCNP. The results were compared with those obtained with the WinXCOM code, for validation. Acceptable and preferable results were obtained for both composites as alternative to other glassy shielding materials. The composite including ITO showed better shielding properties than the composite including ZnO. In terms of radiation shielding, both composites turned out to be better than concrete and close to lead.     

The tetrameric pheromone module SteC‐MkkB‐MpkB‐SteD regulates asexual sporulation,sclerotia formation and aflatoxin production in Aspergillus flavus

For eukaryotes like fungi to regulate biological responses to environmental stimuli, various signalling cascades are utilized, like the highly conserved mitogen‐activated protein kinase (MAPK) pathways. In the model fungus Aspergillus nidulans, a MAPK pathway known as the pheromone module regulates development and the production of secondary metabolites (SMs). This pathway consists five proteins, the three kinases SteC, MkkB and MpkB, the adaptor SteD and the scaffold HamE. In this study, homologs of these five pheromone module proteins have been identified in the plant and human pathogenic fungus Aspergillus flavus. We have shown that a tetrameric complex consisting of the three kinases and the SteD adaptor is assembled in this species. It was observed that this complex assembles in the cytoplasm and that MpkB translocates into the nucleus. Deletion of steC, mkkB, mpkB or steD results in abolishment of both asexual sporulation and sclerotia production. This complex is required for the positive regulation of aflatoxin production and negative regulation of various SMs, including leporin B and cyclopiazonic acid (CPA), likely via MpkB interactions in the nucleus. These data highlight the conservation of the pheromone module in Aspergillus species, signifying the importance of this pathway in regulating fungal development and secondary metabolism.     

The effects of desert dust storms,air pollution,and temperature on morbidity due to spontaneous abortions and toxemia of pregnancy: 5-year analysis

International Journal of Biometeorology - Epidemiological studies have suggested an association between particulate air pollution, increased temperatures, and morbidity related to pregnancy...     

Two calcium‐binding chaperones from the fat body of the Colorado potato beetle,Leptinotarsa decemlineata (Coleoptera: Chrysomelidae) involved in diapause

Molecular chaperones are crucial for the correct folding of newly synthesized polypeptides, in particular, under stress conditions. Various studies have revealed the involvement of molecular chaperones, such as heat shock proteins, in diapause maintenance and starvation; however, the role of other chaperones in diapause and starvation relatively is unknown. In the current study, we identified two lectin‐type chaperones with calcium affinity, a calreticulin (LdCrT) and a calnexin (LdCnX), that were present in the fat body of the Colorado potato beetle, Leptinotarsa decemlineata (Coleoptera: Chrysomelidae) during diapause. Both proteins possessed an N‐globular domain, a P‐arm domain, and a highly charged C‐terminal domain, while an additional transmembrane domain was present in LdCnX. Phylogenetic analysis revealed distinction at the order level. Both genes were expressed in multiple tissues in larval and adult stages, and constitutively throughout development, though a starvation response was detected only for LdCrT. In females, diapause‐related expression analysis in the whole body revealed an upregulation of both genes by post‐diapause, but a downregulation by diapause only for LdCrT. By contrast, males revealed no alteration in their diapause‐related expression pattern in the entire body for both genes. Fat body‐specific expression analysis of both genes in relation to diapause revealed the same expression pattern with no alteration in females and downregulation in males by post‐diapause. This study suggests that calcium‐binding chaperones play similar and possibly gender‐specific roles during diapause.     

Melanocortin-4 Receptor Gene Polymorphisms in Obese Patients

Obesity is a complex disease caused by both genetics and environmental factors. Melanocortin-4 receptor (MC4R) (MIM 155541) gene polymorphisms were reported to be the cause of monogenic obesity in humans. We studied three polymorphisms (Val50Met, Val103Ile, and Ser58Cys) and a mutation (Asn274Ser) of the MC4R gene in 203 obese patients and in 110 healthy subjects in the Turkish population. A high incidence of Val103Ile and Val50Met polymorphisms as well as the Asn274Ser mutation was found in the obese patients, whereas no significant correlation was found regarding the Ser58Cys polymorphism. We conclude that there is a concordance between the polymorphisms (Val103Ile, Val50Met, Ser58Cys) that were first studied in the Turkish population with obesity.