Synthesis,Biological Evaluation,and Molecular Modeling Studies of New 1,3,4-Thiadiazole Derivatives as Potent Antimicrobial Agents

In this work, the synthesis, characterization, and biological activities of a new series of 1,3,4-thiadiazole derivatives were investigated. The structures of final compounds were identified using ¹H-NMR, ¹³C-NMR, elemental analysis, and HRMS. All the new synthesized compounds were then screened for their antimicrobial activity against four types of pathogenic bacteria and one fungal strain, by application of the MIC assays, using Ampicilin, Gentamycin, Vancomycin, and Fluconazole as standards. Among the compounds, the MIC values of 4 and 8 μg/mL of the compounds 3f and 3g , respectively, are remarkable and indicate that these compounds are good candidates for antifungal activity. The docking experiments were used to identify the binding forms of produced ligands with sterol 14-demethylase to acquire insight into relevant proteins. The MD performed about 100 ns simulations to validate selected compounds’ theoretical studies. Finally, using density functional theory (DFT) to predict reactivity, the chemical characteristics and quantum factors of synthesized compounds were computed. These results were then correlated with the experimental data. Furthermore, computational estimation was performed to predict the ADME properties of the most active compound 3f .     

Comparison of first and second heart sounds after mechanical heart valve replacement

In this article, the spectral features of first heart sounds (S1) and second heart sounds (S2), which comprise the mechanical heart valve sounds obtained after aortic valve replacement (AVR) and mitral valve replacement (MVR), are compared to find out the effect of mechanical heart valve replacement and recording area on S1 and S2. For this aim, the Welch method and the autoregressive (AR) method are applied on the S1 and S2 taken from 66 recordings of 8 patients with AVR and 98 recordings from 11 patients with MVR, thereby yielding power spectrum of the heart sounds. Three features relating to frequency of heart sounds and three features relating to energy of heart sounds are obtained. Results show that in comparison to natural heart valves, mechanical heart valves contain higher frequency components and energy, and energy and frequency components do not show common behaviour for either AVR or MVR depending on the recording areas. Aside from the frequency content and energy of the sound generated by mechanical heart valves being affected by the structure of the lungs–thorax and the recording areas, the pressure across the valve incurred during AVR or MVR is a significant factor in determining the frequency and energy levels of the valve sound produced. Though studies on native heart sounds as a non-invasive diagnostic method has been done for many years, it is observed that studies on mechanical heart valves sounds are limited. The results of this paper will contribute to other studies on using a non-invasive method for assessing the mechanical heart valve sounds.     

Patterns of time since last meal revealed by sparse PCA in an observational LC–MS based metabolomics study

In metabolomics studies, liquid chromatography mass spectrometry (LC–MS) provides comprehensive information on biological samples. However, extraction of few relevant metabolites from this large and complex data is cumbersome. To resolve this issue, we have employed sparse principal component analysis (SPCA) to capture the underlying patterns and select relevant metabolites from LC–MS plasma profiles. The study involves a small pilot cohort with 270 subjects where each subject’s time since last meal (TSLM) has been recorded prior to plasma sampling. Our results have demonstrated that both PCA and SPCA can capture the TSLM patterns. Nevertheless, SPCA provides more easily interpretable loadings in terms of selection of relevant metabolites, which are identified as amino acids and lyso-lipids. This study demonstrates the utility of SPCA as a pattern recognition and variable selection tool in metabolomics. Furthermore, amino acids and lyso-lipids are determined as dominating compounds in response to TSLM.     

Thirty-one flavors of Drosophila rab proteins

Rab proteins are small GTPases that play important roles in transport of vesicle cargo and recruitment, association of motor and other proteins with vesicles, and docking and fusion of vesicles at defined locations. In vertebrates, >75 Rab genes have been identified, some of which have been intensively studied for their roles in endosome and synaptic vesicle trafficking. Recent studies of the functions of certain Rab proteins have revealed specific roles in mediating developmental signal transduction. We have begun a systematic genetic study of the 33 Rab genes in Drosophila. Most of the fly proteins are clearly related to specific vertebrate proteins. We report here the creation of a set of transgenic fly lines that allow spatially and temporally regulated expression of Drosophila Rab proteins. We generated fluorescent protein-tagged wild-type, dominant-negative, and constitutively active forms of 31 Drosophila Rab proteins. We describe Drosophila Rab expression patterns during embryogenesis, the subcellular localization of some Rab proteins, and comparisons of the localization of wild-type, dominant-negative, and constitutively active forms of selected Rab proteins. The high evolutionary conservation and low redundancy of Drosophila Rab proteins make these transgenic lines a useful tool kit for investigating Rab functions in vivo.     

Palaeoecology of Upper Pleistocene-Holocene bryozoan and foraminiferal assemblages from Ku?dili (Kadiköy, Istanbul, Turkey)

Bryozoan and foraminiferal assemblages from a core drilled in the Kusdili (Kadiköy, Istanbul) Upper Pleistocene-Holocene sequence were studied. Assemblages are absent from the very basal and top parts but they are well represented all along the middle part of the sequence. All the species found presently live in the Mediterranean. In the area sedimentation seemingly started about 13?000 years ago in very shallow near-shore environments with the deposition of pebbly sediments rapidly evolving to mud. Near the base, the presence of erosional surface allows to recognize three successive sedimentary cycles. Bryozoan and foraminiferal assemblages found in the middle part of the sequence testify to a shallow water, estuarine or lagoonal paleo-environment, in which effects of low salinity waters, more obvious toward the top, could be related to the reestablishment of a connection between the Marmara Sea and the Black Sea through the Bosphorus, about 7000 years BP.     

A partial trisomy 15q due to 15;17 translocation detected by conventional cytogenetic and FISH techniques

We report a case having multiple abnormalities including the simultaneous presence of the heart defect and central nerve system abnormalities, which has been reported in a few cases, and with a partial trisomy 15q. Partial trisomy 15q has been inherited from a balanced translocation carried by his phenotypically normal father, detected by traditional banding and fluorescence in situ hybridization (FISH). Application of FISH using whole chromosome specific library probes, locus specific and repetitive probes allowed us to detect the translocation between chromosomes 15q and 17q. Simultaneous application of probes revealed the position of the translocation. Interestingly, in addition to the chromosomes 15 pericentromeric signals, the use of chromosome 15 beta-satellite III probe demonstrated an extra signal on chromosome 14 in both metaphase, and lighted three signals interphase nuclei which was inherited from his father. This patient is compared with other partial trisomy 15q patients reported in the literature. The results are also discussed in relation to genetic counselling for the possible relation of chromosome abnormality and clinical findings.     

A safer and relatively shorter method for Southern blot hybridization analysis

The study presented here describes a Southern blot hybridization technique which is performed in a shorter time and safer than the classical one. In this study DNA was isolated from a small amount of blood sample and the probe for hybridization was prepared with (35)S by polymerase chain reaction.     

In vivo consequences of cholesterol-24S-hydroxylase (CYP46A1) inhibition by voriconazole on cholesterol homeostasis and function in the rat retina

Cholesterol 24S-hydroxylase (CYP46A1) converts cholesterol into 24S-hydroxycholesterol in neurons and participates in cholesterol homeostasis in the central nervous system, including the retina. We aimed to evaluate the consequences of CYP46A1 inhibition by voriconazole on cholesterol homeostasis and function in the retina. Rats received daily intraperitoneal injections of voriconazole (60 mg/kg), minocycline (22 mg/kg), voriconazole plus minocycline, or vehicle during five consecutive days. The rats were submitted to electroretinography to monitor retinal functionality. Cholesterol and 24S-hydroxycholesterol were measured in plasma, brain and retina by gas chromatography-mass spectrometry. The expression of CYP46A1, and GFAP as a marker for glial activation was analyzed in the retina and brain. Cytokines and chemokines were measured in plasma, vitreous, retina and brain. Voriconazole significantly impaired the functioning of the retina as exemplified by the reduced amplitude and increased latency of the b-wave of the electroretinogram, and altered oscillary potentials. Voriconazole decreased 24S-hydroxycholesterol levels in the retina. Unexpectedly, CYP46A1 and GFAP expression was increased in the retina of voriconazole-treated rats. ICAM-1 and MCP-1 showed significant increases in the retina and vitreous body. Minocycline did not reverse the effects of voriconazole. Our data highlighted the cross talk between retinal ganglion cells and glial cells in the retina, suggesting that reduced 24S-hydroxycholesterol concentration in the retina may be detected by glial cells, which were consequently activated.     

Comparison of two different cryopreservation protocols for freezing goat semen

In this study, two different semen cryopreservation protocols were compared to freeze goat semen. The ejaculates (n = 12) were collected by using electro-ejaculator from six mature bucks (two ejaculates per each buck). Each ejaculate was divided into two groups as Protocol 1 (P1) and Protocol 2 (P2). In P1, semen was diluted directly in an extender containing 15% egg yolk, 300 mM Tris, 28 mM glucose, 95 mM citric acid 5% glycerol to a concentration of 200 × 10⁶ sperm/mL. In P2, after the removal of seminal plasma by centrifugation, the semen sample was diluted with the first portion of milk extender consist of 100 mg/mL skimmed milk powder and 27.75 mM glucose (without glycerol) to a concentration of 400 × 10⁶ sperm/mL. The second portion of the milk extender containing 14% glycerol was added to semen gradually in order to achieve sperm concentration 200 × 10⁶ sperm/mL and 7% glycerol level in the final volume. Extended semen was loaded in 0.25 mL straws, held for 2 h at 4 °C, frozen in nitrogen vapor and stored in liquid nitrogen. Post-thaw motility and live sperm rate (mean ± SEM) were significantly lower (P < 0.05) in P1 as compared to P2 (47.50 ± 1.23% vs. 55.63 ± 1.72%; 80.04 ± 1.29% vs. 84.04 ± 1.08%, respectively). However, live intact, total intact, abnormal, reacted acrosome and DNA damaged sperm rates were similar (P > 0.05) in both protocols. It was concluded that both protocols used in this study provided reasonable post-thaw parameters; however, P2 yielded better motility and live sperm rate compared to P1.