Fluorinated Phthalocyanine/Silver Nanoconjugates for Multifunctional Biological Applications

In this study, a new phthalonitrile derivative namely 4-[(2,4-difluorophenyl)ethynyl]phthalonitrile ( 1 ) and its metal phthalocyanines ( 2 and 3 ) were synthesized. The resultant compounds were conjugated to silver nanoparticles and characterized using transmission electron microscopy (TEM) images. The biological properties of compounds ( 1 – 3 ), their nanoconjugates ( 4 – 6 ), and silver nanoparticles ( 7 ) were examined for the first time in this study. The antioxidant activities of biological candidates ( 1 – 7 ) were studied by applying the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The highest antioxidant activity was obtained 97.47 % for 200 mg/L manganese phthalocyanine-silver nanoconjugates ( 6 ). The antimicrobial and antimicrobial photodynamic therapy (APDT) activities of biological candidates ( 1 – 7 ) were examined using a micro-dilution assay. The highest MIC value was obtained 8 mg/L for nanoconjugate 6 against E. hirae. The studied compounds and their silver nanoconjugates exhibited high APDT activities against all the studied microorganisms. The most effective APDT activities were obtained 4 mg/L for nanoconjugates ( 5 and 6 ) against L. pneumophila and E. hirae, respectively. All the studied biological candidates displayed high cell viability inhibition activities against E. coli cell growth. The biofilm inhibition activities of the tested biological candidates were also investigated against S. aureus and P. Aeruginosa. Biological candidates ( 1 – 6 ) can be considered efficient metal nanoparticle-based materials for multi-disciplinary biological applications.     

Loss of kindlin-1, a human homolog of the Caenorhabditis elegans actin-extracellular-matrix linker protein UNC-112, causes Kindler syndrome

Kindler syndrome is an autosomal recessive disorder characterized by neonatal blistering, sun sensitivity, atrophy, abnormal pigmentation, and fragility of the skin. Linkage and homozygosity analysis in an isolated Panamanian cohort and in additional inbred families mapped the gene to 20p12.3. Loss-of-function mutations were identified in the FLJ20116 gene (renamed “KIND1” [encoding kindlin-1]). Kindlin-1 is a human homolog of the Caenorhabditis elegans protein UNC-112, a membrane-associated structural/signaling protein that has been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM). Thus, Kindler syndrome is, to our knowledge, the first skin fragility disorder caused by a defect in actin-ECM linkage, rather than keratin-ECM linkage.     

Production of resistant starch from taro (Colocasia esculenta L. Schott) corm and determination of its effects on health by in vitro methods

The aim of the study was the production of resistant starch from taro (Colocasia esculenta L. Schott) corm and determination of its effects on health by in vitro methods. Starch was isolated from taro corms with 98% purity, and 10.4±0.5% amylose content. By application of heating, autoclaving, enzymatic debranching, retrogradation, and drying processes to taro starch for two times, resistant starch (RS) content was increased 16 fold (35.1±1.9%, dry basis). The expected glycemic index (eGI) of taro starch and taro resistant starch was determined as 60.6±0.5 and 51.9±0.9, respectively and the decrease in the glycemic index of taro resistant starch was found as statistically significant (P<0.05). The in vitro binding of bile acids by taro starch and taro resistant starch relative to cholesterol decreasing drug cholestyramine were 5.2±0.2% and 7.6±1.7%, respectively.     

Culturalizing politics,hyper-politicizing ‘culture’: ‘White’ vs. ‘Black Turks’ and the making of authoritarian populism in Turkey

This paper focuses on the uses and abuses of two terms, ‘White’ and ‘Black Turk’, which have been significant in the ways modern Turkish society and national identity have been defined and contested in recent decades. Initially emerging in social analysis in the 1990s, ‘White Turk’ was a metaphor for and critique of the class culture, subjectivity and worldviews of the ‘new middle classes’ in a period of rapid integration to neoliberalism and globalized capitalism. Over time, both White and Black Turks have come to be used as part of a politics of identity and a politics of authenticity to characterize who are seen as the ‘authentic self’ and inauthentic others of national identity and to assert different visions for the future of Turkish society. White Turk has been adopted as an identity by outspoken members of the media and business elite, whereas its binary opposite, Black Turk, has been appropriated by Islamist politicians of the Justice and Development Party (AKP) as a metaphor to characterize the marginalization and purported oppression of their conservative Muslim constituency. As White and Black Turks were adopted as self-proclaimed identities, they provided a basis for a culturalist depiction of Turkish society, contributing over time to an increasingly divisive politics. Even though the AKP initially used the reference to White and Black Turks to appeal to specific demands for inclusion, as it increased its grip on power, it also (hyper)politicized the terms to articulate nativist claims to authenticity. In recent years, this nativist populism has been used to justify increasing authoritarianism and to delegitimize belonging and political participation of those deemed inauthentic others of the body politics.     

The role of circadian rhythm on the pharmacokinetic of methotrexate in streptozotocin-induced diabetes mellitus rats

Chronopharmacokinetic studies have been conducted both in animals and humans. Anticancer agents are of great interest due to their narrow therapeutic range and large pharmacokinetic variability. It was reported that the pharmacokinetics of MTX showed a circadian rhythm in rats and humans. Since diabetes-induced physiological changes can affect pharmacokinetics of drugs, it was reported that MTX blood concentration in diabetic rats was higher than that of the control groups. The present study was designed to elucidate whether these diabetes-induced changes in pharmacokinetics occurred during the day and thus administered MTX at four different times in streptozotocin-induced diabetes mellitus (SIDM) rats. Blood samples were drawn at 5, 15, 30, and 60 min after IV infusion of MTX in both the SIDM and control groups. Control and SIDM Area under the concentration - time curve (AUC) values showed a significant circadian rhythm with a peak located in mid-dark phase at 14:00. Clearance values were significantly low at 14:00 in the diabetic group when compared to other periods and the control group. The MTX AUC was increased when treatment with dexamethasone was given to suppress the endogenous production of corticosterone in both control and SIDM rats. These results suggest that the extent of MTX pharmacokinetics varies with the time of day in the SIDM rats and these variations might be related to changes in corticosterone concentrations.     

An efficient gene transfer system for the pimaricin producer Streptomyces natalensis

Streptomyces natalensis produces the antifungal polyene macrolide pimaricin. Genetic manipulation of its biosynthetic genes has been hampered by the lack of efficient gene transfer systems. We have developed a gene transfer system based on intergeneric conjugation from Escherichia coli. Using this approach, we managed to attain transformation efficiencies of 1 x 10(-4) exconjugants per recipient when using self-replicating vectors such as pHZ1358. The use of integrative vectors such as pSET152 or pSOK804 resulted in significantly lower efficiencies. Site-specific integration or the use of self-replicating plasmids did not affect pimaricin production or the essential functions of S. natalensis. Use of DNA methylation proficient E. coli donor strains resulted in no transformants, indicating the presence of methyl-specific restriction systems in S. natalensis. This methodology will enable easier manipulation of the genes responsible for pimaricin biosynthesis, and could prove valuable for the generation of new designer polyene macrolides with better antifungal activity and pharmacological properties. As an example of the validity of the method, we describe the introduction of Supercos-1-derived cosmid vectors into S. natalensis in order to promote gene replacements by double crossover recombination.     

Overexpression of polyphosphate kinase gene (ppk) increases bioinsecticide production by Bacillus thuringiensis

Polyphosphate (polyP), synthesized by polyP kinase (PPK) using the terminal phosphate of ATP as substrate, performs important functions in every living cell. The present work reports on the relationship between polyP metabolism and bioinsecticide production in Bacillus thuringiensis subsp. israelensis (Bti). The ppk gene of Bti was cloned into vector pHT315 and the effect of its overexpression on endotoxin production was determined. Endotoxin production by the recombinant strain was found to be consistently higher than that by the wild type strain and the strain that carried the empty plasmid. The toxicity of the recombinant mutant strain (LC₅₀ 5.8 ± 0.6 ng ml^?1) against late 2nd instar Culex quinquefasciatus was about 7.7 times higher than that of Bti (LC₅₀ 44.9 ± 7 ng ml^?1). To our knowledge this is the first reported study which relates polyP metabolism with bioinsecticide biosynthesis.     

Polyhydroxyalkanoate accumulation in Streptomyces coelicolor affected by SCO7613 gene region

Polyhydroxyalkanoate (PHA) is stored as an important carbon and energy source in bacterial cells. For biomedical applications, gram-positive bacteria can be better sources of PHAs, since they lack outer membrane lipopolysaccharide. Although gram-positive Streptomyces coelicolor A3(2) has been indicated as a high potential PHA producer, pha C gene that encodes the key enzyme PHA synthase in the metabolic pathway is not determined in its genome. BLAST search results of the GenBank database argued that SCO7613 could specify a putative polyhydroxyalkanoate synthase (PhaC) responsible for PHA biosynthesis. Deduced amino acid sequence of SCO7613 showed the presence of conserved lipase box like sequence, ⁵⁵⁵GASAG⁵⁵⁹, in which serine residue was present as the active nucleophile. Present study describes deletion of putative S. coelicolor pha C gene via PCR dependent method. We showed that SCO7613 is not an essential gene in S. coelicolor and its deletion affected PHA accumulation negatively although it is not ceased. Transcomplementation abolished the mutant phenotype, demonstrating that the decrease in PHA resulted from the deletion of SCO7613.