Concentration and localization of zinc during seed development and germination in wheat

In a field experiment, the effect of foliar Zn applications on the concentration of Zn in seeds of a bread wheat cultivar ( Triticum aestivum L. cv. Balatilla) was studied during different stages of seed development. In addition, a staining method using dithizone (DTZ: diphenyl thiocarbazone) was applied to (1) study the localization of Zn in seeds, (2) follow the remobilization of Zn during germination, and (3) develop a rapid visual Zn screening method for seed and flour samples. In all seed development stages, foliar Zn treatments were effective in increasing seed Zn concentration. The highest Zn concentration in the seeds was found in the first stage of seed development (around the early milk stage); after this, seed Zn concentration gradually decreased until maturity. When reacting with Zn, DTZ forms a redcolored complex. The DTZ staining of seed samples revealed that Zn is predominantly located in the embryo and aleurone parts of the seeds. After 36 h of germination, the coleoptile and roots that emerged from seeds showed very intensive red color formation and had Zn concentrations up to 200 mg kg⁻¹, indicating a substantial remobilization of Zn from seed pools into the developing roots (radicle) and coleoptile. The DTZ staining method seems to be useful in ranking flour samples for their Zn concentrations. There was a close relationship between the seed Zn concentrations and spectral absorbance of the methanol extracts of the flour samples stained with DTZ. The results suggest that (1) accumulation of Zn in seeds is particularly high during early seed development, (2) Zn is concentrated in the embryo and aleurone parts, and (3) the DTZ staining method can be used as a rapid, semiquantitative method to estimate Zn concentrations of flour and seed samples and to screen genotypes for their Zn concentrations in seeds.     

Synthesis and cellular bioactivities of novel isoxazole derivatives incorporating an arylpiperazine moiety as anticancer agents

In our endeavour towards the development of effective anticancer therapeutics, a novel series of isoxazole-piperazine hybrids were synthesized and evaluated for their cytotoxic activities against human liver (Huh7 and Mahlavu) and breast (MCF-7) cancer cell lines. Within series, compounds 5l-o showed the most potent cytotoxicity on all cell lines with IC₅₀ values in the range of 0.3–3.7?μM. To explore the mechanistic aspects fundamental to the observed activity, further biological studies with 5m and 5o in liver cancer cells were carried out. We have demonstrated that 5m and 5o induce oxidative stress in PTEN adequate Huh7 and PTEN deficient Mahlavu human liver cancer cells leading to apoptosis and cell cycle arrest at different phases. Further analysis of the proteins involved in apoptosis and cell cycle revealed that 5m and 5o caused an inhibition of cell survival pathway through Akt hyperphosphorylation and apoptosis and cell cycle arrest through p53 protein activation.     

Mitofusin gain and loss of function drive pathogenesis in Drosophila models of CMT2A neuropathy

Charcot–Marie–Tooth disease type 2A (CMT2A) is caused by dominant alleles of the mitochondrial pro‐fusion factor Mitofusin 2 (MFN2). To address the consequences of these mutations on mitofusin activity and neuronal function, we generate Drosophila models expressing in neurons the two most frequent substitutions (R94Q and R364W, the latter never studied before) and two others localizing to similar domains (T105M and L76P). All alleles trigger locomotor deficits associated with mitochondrial depletion at neuromuscular junctions, decreased oxidative metabolism and increased mtDNA mutations, but they differently alter mitochondrial morphology and organization. Substitutions near or within the GTPase domain (R94Q, T105M) result in loss of function and provoke aggregation of unfused mitochondria. In contrast, mutations within helix bundle 1 (R364W, L76P) enhance mitochondrial fusion, as demonstrated by the rescue of mitochondrial alterations and locomotor deficits by over‐expression of the fission factor DRP1. In conclusion, we show that both dominant negative and dominant active forms of mitofusin can cause CMT2A‐associated defects and propose for the first time that excessive mitochondrial fusion drives CMT2A pathogenesis in a large number of patients.     

Propranolol,a β-adrenoceptor antagonist,worsens liver injury in a model of non-alcoholic steatohepatitis

Prazosin an α1-adrenoceptor (AR) antagonist has been shown to reduce liver injury in a mouse model of non-alcoholic steatohepatitis (NASH) and is suggested as a potential treatment of NASH especially given its concomitant anti-fibrotic properties. The effect however, of β-AR blockade in non-cirrhotic NASH is unknown and is as such investigated here. In the presence of the β-blocker propranolol (PRL), mice fed normal chow or a half methionine and choline deficient diet, supplemented with ethionine (HMCDE), to induce NASH, showed significantly enhanced liver injury, as evidenced by higher hepatic necrosis scores and elevated serum aminotransferases (ALT). Mechanistically, we showed that murine hepatocytes express α and β adrenoceptors; that PRL directly induces hepatocyte injury and death as evidenced by increased release of lactate dehydrogenase, FASL and TNF-α from hepatocytes in the presence of PRL; and that PRL activated the apoptotic pathway in primary hepatocyte cultures, as indicated by upregulation of Fas receptor and caspase-8 proteins. The β-AR antagonist PRL therefore appears to enhance liver injury through induction of hepatocyte death via the death pathway. Further studies are now required to extrapolate these findings to humans but meanwhile, β-AR antagonists should be avoided or used with caution in patients with non-cirrhotic NASH as they may worsen liver injury.     

Different Roles for Tet1 and Tet2 Proteins in Reprogramming-Mediated Erasure of Imprints Induced by EGC Fusion

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Highlights? EGCs can erase DNA methylation at ICRs in somatic cells after fusion ? EGCs selectively induce 5hmC accumulation at ICRs in the somatic genome ? Conversion of 5mC to 5hmC at these imprinted domains requires Tet1 ? Tet2 depletion results in delayed reprogramming by EGCs     

Which is the best anthropometric technique to identify obesity: body mass index, waist circumference or waist-hip ratio?

This study was designed to define the most suitable anthropometric technique among body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) as indices of obesity in adult people living in Adana, a Southern province of Turkey. A random sample design was used. A total of 900 individuals (men and non-pregnant women aged 25-65 years) were enrolled in the study. Of subjects, 50.9% were females. Anthropometric measurements were performed. Data were analysed using statistical package program. The prevalence of obesity among adults living in Adana was 20.8% 28.4% when defined using BMI, 30.5% by WC and 15.8% 42.0% by WHR. Truncal obesity and gynoid obesity showed similar prevalence with 26.6%, in the same age group. Waist circumference, BMI and WHR identified different proportions of the population, as measured for obesity prevalence. The most common methods for diagnosing overweight and obesity are based on BMI (kg/m2). However, BMI is suboptimal marker for total body fat percentage and even less suitable to assess body fat distribution. WHR is the most useful measure of obesity and the best simple anthropometric index in predicting a wide range of risk factors and related health conditions.     

Fluoxetine Partly Exerts its Actions Through GABA: A Neurochemical Evidence

Fluoxetine, as a serotonin re-uptake inhibitor augments serotonin concentration within the synapse by inhibiting the serotonin transporter. The contribution of amino acids has also been shown in depression. We hypothesized that fluoxetine exerts its actions at least in part by intervening brain signaling operated by amino acid transmitters. Therefore the aim of this study is to supply neurochemical evidence that fluoxetine produces changes in amino acids in cerebrospinal fluid of rats. Sprague-Dawley rats were anesthetized and concentric microdialysis probes were implanted stereotaxically into the right lateral ventricle. Intraperitoneal fluoxetine (2.5 or 5 mg/kg) or physiological saline was administered and the probes were perfused with artificial cerebrospinal fluid at a rate of 1 μl/min. In the chronic fluoxetine group, the rats were treated daily with oral fluoxetine solution or inert syrup for 3 weeks. The microdialysis probes were placed on the 21st day and perfused the next day. Fluoxetine was ineffective in changing the cerebrospinal fluid GABA levels at the dose of 2.5 mg/kg but produced a significant increase in the perfusates following injection of 5 mg/kg of fluoxetine (P < 0.05). Oral fluoxetine administration (5 mg/kg) for 21 days also elevated the CSF GABA levels by approximately 2-fold (P < 0.05). l-glutamic acid levels were not affected in all groups. These neurochemical findings show that fluoxetine, a selective serotonin re-uptake inhibitor affects brain GABA levels indirectly, and our results suggest that acute or chronic effects may be involved in beneficial and/or adverse effects of the drug.