Synthesis of some 4-arylidenamino-4H-1,2,4-triazole-3-thiols and their antituberculosis activity

The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new triazoles were synthesized and evaluated for antituberculosis activity. A series of 4-arylidenamino-4H-1,2,4-triazole-3-thiol derivatives (2a–n) were synthesized from the treatment of 4-amino-4H-1,2,4-triazoles-3-thiol (1) with the respective aldehydes and were evaluated for antituberculosis activity against Mycobacterium tuberculosis H₃₇Rv (ATCC 27294), using the BACTEC 460 radiometric system and BACTEC 12B medium. Compound 2k showed an intereting activity at 6.25 μg/mL with a 87 percentage inhibition.     

Parkin‐independent mitophagy requires Drp1 and maintains the integrity of mammalian heart and brain

Mitochondrial dynamics and mitophagy have been linked to cardiovascular and neurodegenerative diseases. Here, we demonstrate that the mitochondrial division dynamin Drp1 and the Parkinson's disease‐associated E3 ubiquitin ligase parkin synergistically maintain the integrity of mitochondrial structure and function in mouse heart and brain. Mice lacking cardiac Drp1 exhibited lethal heart defects. In Drp1KO cardiomyocytes, mitochondria increased their connectivity, accumulated ubiquitinated proteins, and decreased their respiration. In contrast to the current views of the role of parkin in ubiquitination of mitochondrial proteins, mitochondrial ubiquitination was independent of parkin in Drp1KO hearts, and simultaneous loss of Drp1 and parkin worsened cardiac defects. Drp1 and parkin also play synergistic roles in neuronal mitochondrial homeostasis and survival. Mitochondrial degradation was further decreased by combination of Drp1 and parkin deficiency, compared with their single loss. Thus, the physiological importance of parkin in mitochondrial homeostasis is revealed in the absence of mitochondrial division in mammals.     

Partial Purification and Some Interesting Properties of Glutathione Peroxidase from Liver of Camel (<Emphasis Type="Italic">Camelus dromedarius</Emphasis>)

Climate change and increasing temperatures are global concerns. Well adapted to desert life, the camel (Camelus dromedarius) lives most of its life under high environmental stress and represents an ideal model for studying desert adaptation among mammals. Glutathione peroxidase is the principal antioxidant defense system capable of protecting cells from oxidative stress. Glutathione Peroxidase from camel liver was purified (11.64-fold purification with 1.73% yield) and characterized The molecular weight of the enzyme was estimated to be about 69 kDa by gel filtration and 34 kDa by SDS-PAGE, implying dimeric structure of the protein. An optimum temperature of 47°C and an optimum pH of 7.8 were found. This enzyme is a typical SH-enzyme that is inhibited by D,L-dithiothreitol and β-mercaptoethanol and sensitive to bivalent cations. The enzyme had common specificity toward hydroperoxides and high specificity for reduced glutathione. The K_m and V_max values for hydrogen peroxide and reduced glutathione were 0.57 and 2.10 mM and 1.11 and 0.87 U/mg, respectively. The purified enzyme contained 16 ng of selenium per mg of protein. Our results show that the camel glutathione peroxidse exhibits properties different of those reported for other mammalian species. Lower molecular weight, homodimeric structure, higher optimum temperature, relatively low optimum pH, high affinity for hydrogen peroxide at low concentration of reduced glutathione and very low content of selenium could be explained by adaptation of the camel to living in the desert under intense environmental stress.     

Evaluation of haploidization efficiency in winter squash (Cucurbita maxima Duch.) and pumpkin (Cucurbita moschata Duch.) through anther culture

The production of large numbers of haploids is the crucial point of the dihaploidisation process. Although in vitro haploid plants were successfully produced by irradiated pollen technique in winter squash (Cucurbita maxima Duch.) and pumpkin (Cucurbita moschata Duch.), the frequency is still insufficient for using in a large-scale breeding programme. Thus, the present study was conducted to determine the efficacy of the anther culture technique on the production of in vitro haploids in the aforementioned species for which there have been no successful reports concerning by androgenesis. The anthers at uninucleate microspore stage were collected at different florescence times and then cultured on a solid MS medium supplemented by different combinations of 2,4-D (2,4-dichlorophenoxyacetic acid), BAP (6-benzylaminopurine), KN (kinetin) with the constant addition of NAA (naphthalene acetic acid) to induce callogenesis, embryogenesis and plantlet initiation. The combination of PGR, genotype and anther collection time played an important role in the androgenic response. The highest response was obtained from 57S?21 and G9 lines with the combination of 2.0 or 4.0 mg/l BAP?+?0.05 mg/l NAA (E6 medium) at the first anther collection time. Plantlets were regenerated and rooted on MS medium supplemented by 0.01 mg/l IAA. In total, 74 plants were recovered and propagated with micro-cuttings. The ploidy analyses revealed that 35 plants (47.3?%) were haploid (n?=?20), and the others (52.7?%) were diploid (2n?=?40).     

Coupling between Catalytic Loop Motions and Enzyme Global Dynamics

Catalytic loop motions facilitate substrate recognition and binding in many enzymes. While these motions appear to be highly flexible, their functional significance suggests that structure-encoded preferences may play a role in selecting particular mechanisms of motions. We performed an extensive study on a set of enzymes to assess whether the collective/global dynamics, as predicted by elastic network models (ENMs), facilitates or even defines the local motions undergone by functional loops. Our dataset includes a total of 117 crystal structures for ten enzymes of different sizes and oligomerization states. Each enzyme contains a specific functional/catalytic loop (10–21 residues long) that closes over the active site during catalysis. Principal component analysis (PCA) of the available crystal structures (including apo and ligand-bound forms) for each enzyme revealed the dominant conformational changes taking place in these loops upon substrate binding. These experimentally observed loop reconfigurations are shown to be predominantly driven by energetically favored modes of motion intrinsically accessible to the enzyme in the absence of its substrate. The analysis suggests that robust global modes cooperatively defined by the overall enzyme architecture also entail local components that assist in suitable opening/closure of the catalytic loop over the active site.     

Combined point mutations in codon 12 and 13 of KRAS oncogene in prostate carcinomas

Prostate cancer is a common malignancy that develops by structural mutation(s) and/or other genetic alterations in specific genes.The G to T transversions in codon 12 and C to T transitions in codon 13 of KRAS proto-oncogene are predominant point mutations that occur in about 20% of different cancers in human. In the current study it was aimed to investigate the prevalence and predictive significance of KRAS mutations in patients with prostate carcinomas. In a total of 30 fresh tumoural tissue specimens were investigated in patients with prostate carcinoma. All tumoural specimens were histo-pathologically diagnosed and genotyped for codon 12, 13 KRAS point mutations by reverse hybridisation and direct sequencing methods. KRAS mutations were found in 12 (40%) samples with 29 samples deriving from adenocarcinomas and 1 sample was small cell prostate carcinoma. In 1 (3.44%) sample codon 12 was found to be mutated and in 2 (6.8%) samples codon 13 and in 9 (31%) samples combined codon 12 and 13 were found to be mutated particularly in higher grade of tumoural tissues. Our study, based on representative collection of human prostate tumours, indicates that combined mutations in codons 12 and 13 KRAS are relatively infrequent and most commonly occur in prostate carcinomas.     

In vitro genotoxic effects of four Helichrysum species in human lymphocytes cultures

Helichrysum sanguineum, Helichrysum pamphylicum, Helichrysum orientale, Helichrysum noeanum (Asteraceae) are medicinal plants. For centuries, they have been used as tea in Turkey because of their medicinal properties. So far no scientific evidence has been found in a literature survey regarding the genotoxic effects of these plants. This work evaluated the genotoxic effects on human lymphocyte cultures induced by methanol extracts of these plants, assayed in different concentrations (0.01, 0.05, 0.1, 0.5 and 1 mg/mL). According to the results, Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum induced the formation of micronuclei and decreased the mitotic and replication indexes. Helichrysum orientale did not affect these parameters, whereas Helichrysum noeanum, Helichrysum pamphylicum and Helichrysum sanguineum were clearly genotoxic. They should therefore not be used freely in alternative medicine, although their antiproliferative activity may suggest antimitotic and anticarcinogenic properties. Helichrysum orientale could be used in alternative medicine.     

<Emphasis Type="Italic">Bracon (Lucobracon) iskilipus</Emphasis> sp. n. (Hymenoptera: Braconidae: Braconinae) from the Central Black Sea region of Turkey

During the studies on the Turkish Braconidae, a new species Bracon (Lucobracon) iskilipus sp. n. from the Turkish Central Black Sea region was recorded. Bracon (Lucobracon) iskilipus sp. n. was described, its morphological diagnostic characters were illustrated and it was compared with the related Bracon (Lucobracon) moczari Papp.     

Analysis of essential oil of Coridothymus capitatus (L.) and its antibacterial and antifungal activity

The water-distilled essential oil the leaves of Coridothymus capitatus were analyzed by GC/MS and also analyzed by direct thermal desorption GC/MS. Comparison was made between two analyses techniques. The essential oil consisted mainly of monoterpenes 98.9%, while oxygenated hydrocarbons were identified as 55.6 % and non-oxygenated hydrocarbons as 43.6%. As major components were found carvacrol (35.6%), p-cymene (21.0%), thymol (18.6%), gamma-terpinene (12.3%), alpha-terpinene (3.2%), beta-myrcene (3.0%) and alpha-thujene (1.3%) by hydrodistillation and by the GC/MS method. The direct thermal desorption GC/MS analysis also showed the same major components, namely carvacrol (51.6%), thymol (21.7%), p-cymene (9.7%) gamma-terpinene (8.2%), alpha-terpinene (1.64%). The essential oil of C. capitatus showed strong activity against S. aureus, P. vulgaris, P. aeruginosa, E. coli, K. pneumonia, B.