Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications

There is evidence for increased levels of circulating reactive oxygen species (ROS) in diabetics, as indirectly inferred by the findings of increased lipid peroxidation and decreased antioxidant status. Direct measurements of intracellular generation of ROS using fluorescent dyes also demonstrate an association of oxidative stress with diabetes. Although phenolic compounds attenuate oxidative stress-related tissue damage, there are concerns over toxicity of synthetic phenolic antioxidants and this has considerably stimulated interest in investigating the role of natural phenolics in medicinal applications. Curcumin (the primary active principle in turmeric, Curcuma longa Linn.) has been claimed to represent a potential antioxidant and antiinflammatory agent with phytonutrient and bioprotective properties. However there are lack of molecular studies to demonstrate its cellular action and potential molecular targets. In this study the antioxidant effect of curcumin as a function of changes in cellular ROS generation was tested. Our results clearly demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and thapsigargin-induced ROS generation in cells from control and diabetic subjects. The pattern of these ROS inhibitory effects as a function of dose-dependency suggests that curcumin mechanistically interferes with protein kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca2+ influx suggest that a rise in cytosolic Ca2+ may be a trigger for increased ROS generation. We suggest that the antioxidant and antiangeogenic actions of curcumin, as a mechanism of inhibition of Ca2+ entry and PKC activity, should be further exploited to develop suitable and novel drugs for the treatment of diabetic retinopathy and other diabetic complications

Omega Production in pp Collisions

A model-independent irreducible tensor formalism which has been developed earlier to analyze measurements of $\vec{p}\vec{p}\to pp \pi^\circ$, is extended to present a theoretical discussion of $\vec{p}\vec{p}\to pp \omega$ and the polarization of $\omega$ in $pp\to pp \vec{\omega}$. The recent measurement of unpolarized differential cross section for $pp\to pp \omega$ is analyzed using this theoretical formalism.Comment: 5 pages (double column), no figures, uses revtex

Impact of remittances on economic growth in developing countries: The role of openness

The paper examines the empirical relationship between remittances and economic growth for a sample of 62 developing countries over the time period 1990–2014. Remittances seem to promote growth only in the ‘more open’ countries. That is because remittances are in themselves not sufficient for growth. The extent of the benefit depends on domestic institutions and macroeconomic environment in the receiving country. Unlike the ‘less open’ countries, ‘more open’ countries have better institutions and better financial markets to take advantage of the remittances income and channelise them into profitable investments which, in turn, accelerates the rate of economic growth in these countries.N/

Genotoksičnost metalnih nanočestica: osvrt na podatke istraživanja In vivo

With increasing production and application of a variety of nanomaterials (NMs), research on their cytotoxic and genotoxic potential grows, as the exposure to these nano-sized materials may potentially result in adverse health effects. In large part, indications for potential DNA damaging effects of nanoparticles (NPs) originate from inconsistent in vitro studies. To clarify these effects, the implementation of in vivo studies has been emphasised. This paper summarises study results of genotoxic effects of NPs, which are available in the recent literature. They provide indications that some NP types cause both DNA strand breaks and chromosomal damages in experimental animals. Their genotoxic effects, however, do not depend only on particle size, surface modifi cation (particle coating), and exposure route, but also on exposure duration. Currently available animal studies may suggest differing mechanisms (depending on the duration of exposure) by which living organisms react to NP contact. Nevertheless, due to considerable inconsistencies in the recent literature and the lack of standardised test methods - a reliable hazard assessment of NMs is still limited. Therefore, international organisations (e.g. NIOSH) suggest utmost caution when potential exposure of humans to NMs occurs, as long as evidence of their toxicological and genotoxic effect(s) is limited.S povećanjem proizvodnje i primjene niza različitih nanomaterijala (NM) raste i potreba istraživanja njihovih mogućih citotoksičnih i genotoksičnih učinaka kao i drugih štetnih učinaka na zdravlje u uvjetima profesionalne ili opće izloženost ljudi. Indikacije potencijanog oštećenja DNA kojeg uzrokuju nanočestice u velikoj mjeri proizlaze iz nedosljednih in vitro ispitivanja. Kako bi se razjasnili ti učinci, naglašena je potreba provedbe in vivo ispitivanja. Ovaj pregledni rad sažima rezultate procjene genotoksičnih učinaka nanočestica koji su objavljeni u novijoj stručnoj i znanstvenoj literaturi. Navedeni rezultati pokazuju da određene nanočestice uzrokuju lomove u molekuli DNA i oštećuju kromosome u eksperimentalnim životinjama. Njihovi genotoksični učinci ne ovise samo o veličini čestice, modifi kaciji površine (oblaganje čestice) i načinu izlaganja, već i o trajanju izloženosti nanočesticama. Postojeća istraživanja provedena na životinjama upućuju na različite mehanizme koji ovise o trajanju izlaganja i pomoću kojih živi organizmi reagiraju na doticaj s nanočesticama. Međutim postoje brojne nedosljednosti u novijoj literaturi, a standardne testne metode nisu dostupne pa je stoga pouzdanija procjena opasnosti od izlaganja nanomaterijalima u ljudi još uvijek veoma ograničena. Stoga se u međunarodnim dokumentima savjetuje oprez prilikom svakog izlaganja ljudi nanomaterijalima kako bi se spriječili mogući opći toksični genotoksični učinci

Unified approach to photo and electro-production of mesons with arbitrary spins

A new approach to identify the independent amplitudes along with their partial wave multipole expansions, for photo and electro-production is suggested,which is generally applicable to mesons with arbitrary spin-parity. These amplitudes facilitate direct identification of different resonance contributions.Comment: 11 page

Genetic structure of a small closed population of the New Zealand white rabbit through pedigree analyses

[EN] The genetic structure of a small population of New Zealand White rabbits maintained at the Sheep Breeding and Research Station, Sandynallah, The Nilgiris, India, was evaluated through pedigree analyses. Data on pedigree information (n=2503) for 18 yr (1995-2012) were used for the study. Pedigree analysis and the estimates of population genetic parameters based on the gene origin probabilities were performed. The analysis revealed that the mean values of generation interval, coefficients of inbreeding and equivalent inbreeding were 1.49 yr, 13.23 and 17.59%, respectively. The proportion of population inbred was 100%. The estimated mean values of average relatedness and individual increase in inbreeding were 22.73 and 3.00%, respectively. The percentage increase in inbreeding over generations was 1.94, 3.06 and 3.98 estimated through maximum generations, equivalent generations and complete generations, respectively. The number of ancestors contributing the majority of 50% genes (fa50) to the gene pool of reference population was only 4, which might have led to reduction in genetic variability and increased the amount of inbreeding. The extent of genetic bottleneck assessed by calculating the effective number of founders (fe) and the effective number of ancestors (fa), as expressed by the fe/fa ratio was 1.1, which is indicative of the absence of stringent bottlenecks. Up to 5th generation, 71.29% pedigree was complete, reflecting the well maintained pedigree records. The maximum known generations were 15, with an average of 7.9, and the average equivalent generations traced were 5.6, indicating a fairly good depth in pedigree. The realized effective population size was 14.93, which is very critical, and with the increasing trend of inbreeding the situation has been assessed as likely to become worse in future. The proportion of animals with the genetic conservation index (GCI) greater than 9 was 39.10%, which can be used as a scale to use such animals with higher GCI to maintain balanced contribution from the founders. From the study, it was evident that the herd was completely inbred, with a very high inbreeding coefficient, and the effective population size was critical. Recommendations were made to reduce the probability of deleterious effects of inbreeding and to improve genetic variability in the herd. The present study can help in carrying out similar studies to meet the demand for animal protein in developing countries.The authors acknowledge the support provided by Tamil Nadu Veterinary and Animal Sciences University (TANUVAS) for successful completion of the study.Sakthivel, M.; Balasubramanyam, D.; Kumarasamy, P.; Raja, A.; Anilkumar, R.; Gopi, H.; Devaki, A. (2018). Genetic structure of a small closed population of the New Zealand white rabbit through pedigree analyses. World Rabbit Science. 26(2):101-112. doi:10.4995/wrs.2018.7426SWORD101112262Alderson G.I.H. 1992. A system to maximize the maintenance of genetic variability in small populations. In L. Alderson & I. Bodo (ed). Genetic Conservation of Domestic Livestock II. CABI, Wallingford, UK, 18-29.Boichard D., Maignel L., Verrier E. 1997. The value of using probabilities of gene origin to measure genetic variability in a population. Genet. Sel. Evol., 29: 5-23. https://doi.org/10.1186/1297-9686-29-1-5Cervantes I., Goyache F., Molina A., Valera M., Gutiérrez J.P. 2008. Application of individual increase in inbreeding to estimate realized effective sizes from real pedigrees. J. Anim. Breed. Genet., 125: 301-310. https://doi.org/10.1111/j.1439-0388.2008.00755.xDuchev Z., Distl O., Groeneveld E. 2006. Early warning system for loss of diversity in European livestock breeds. Arch. Anim. Breed., 49: 521-531. https://doi.org/10.5194/aab-49-521-2006Dunner S., Checa M.L., Gutierrez J.P., Martin J.P., Cañon J. 1998. Genetic analysis and management in small populations: the Asturcon pony as an example. Genetics Selection Evolution 30: 397-405. https://doi.org/10.1186/1297-9686-30-4-397Falconer D.S., Mackay T.F.C. 1996. Introduction to Quantitative Genetics. Longmans Green, Harlow, Essex, UK.Fernández J., Toro M.A., Caballero A. 2003. Fixed contributions designs vs. minimization of global conancestry to control inbreeding in small populations. Genetics, 165: 885-894.González-Recio O., López de Maturana E., Gutiérrez J.P. 2007. Inbreeding depression on female fertility and calving ease in Spanish dairy cattle. J. Dairy Sci., 90: 5744-5752. https://doi.org/10.3168/jds.2007-0203Gowane G.R., Chopra A., Misra S.S., Prince L.L.L. 2014. Genetic diversity of a nucleus flock of Malpura sheep through pedigree analyses. Small Ruminant Res., 120: 35-41. https://doi.org/10.1016/j.smallrumres.2014.04.016Goyache F., Gutiérrez J.P., Fernández I., Gomez E., Alvarez I., Díez J., Royo I.J. 2003. Using pedigree information to monitor genetic variability of endangered populations: the Xalda sheep breed of Asturias as an example. J. Anim. Breed. Genet., 120: 95-103. https://doi.org/10.1046/j.1439-0388.2003.00378.xGutiérrez J.P., Altarriba J., Díaz C., Quintanilla A.R., Cañón J., Piedrafita J. 2003. Genetic analysis of eight Spanish beef cattle breeds. Genet. Sel. Evol., 35: 43-64. https://doi.org/10.1051/gse:2002035Gutiérrez J.P., Cervantes I., Goyache F. 2009. Improving the estimation of realized effective population sizes in farm animals. J. Anim. Breed. Genet., 126: 327-332.https://doi.org/10.1111/j.1439-0388.2009.00810.xGutiérrez J.P., Cervantes I., Molina A., Valera M., Goyache F. 2008. Individual increase in inbreeding allows estimating realized effective sizes from pedigrees. Genet. Sel. 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Equivalent effective population size mating as a useful tool in the genetic management of the Ibicenco rabbit breed (Conill Pages d'Eivissa). Czech J. Anim. Sci., 61: 108-116. https://doi.org/10.17221/8783-CJASMartínez R.A., García D., Gallego J.L., Onofre G., Pérez J., Cañón J. 2008. Genetic variability in Colombian Creole cattle populations estimated by pedigree information. J. Anim. Sci., 86: 545-552. https://doi.org/10.2527/jas.2007-0175Meuwissen T.H.E. 1991. Expectation and variance of genetic gain in open and closed nucleus and progeny testing schemes. Anim. Prod., 53: 133-141. https://doi.org/10.1017/S0003356100020043Meuwissen T.H.E. 2009. Towards consensus on how to measure neutral genetic diversity? J. Anim. Breed. Genet., 126: 333-334. https://doi.org/10.1111/j.1439-0388.2009.00839.xMeuwissen T.I., Luo Z. 1992. Computing inbreeding coefficients in large populations. Genet. Sel. 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Histone deacetylases suppress cgg repeat-induced neurodegeneration via transcriptional silencing in models of Fragile X Tremor Ataxia Syndrome

Fragile X Tremor Ataxia Syndrome (FXTAS) is a common inherited neurodegenerative disorder caused by expansion of a CGG trinucleotide repeat in the 59UTR of the fragile X syndrome (FXS) gene, FMR1. The expanded CGG repeat is thought to induce toxicity as RNA, and in FXTAS patients mRNA levels for FMR1 are markedly increased. Despite the critical role of FMR1 mRNA in disease pathogenesis, the basis for the increase in FMR1 mRNA expression is unknown. Here we show that overexpressing any of three histone deacetylases (HDACs 3, 6, or 11) suppresses CGG repeat-induced neurodegeneration in a Drosophila model of FXTAS. This suppression results from selective transcriptional repression of the CGG repeat-containing transgene. These findings led us to evaluate the acetylation state of histones at the human FMR1 locus. In patient-derived lymphoblasts and fibroblasts, we determined by chromatin immunoprecipitation that there is increased acetylation of histones at the FMR1 locus in pre-mutation carriers compared to control or FXS derived cell lines. These epigenetic changes correlate with elevated FMR1 mRNA expression in pre-mutation cell lines. Consistent with this finding, histone acetyltransferase (HAT) inhibitors repress FMR1 mRNA expression to control levels in pre-mutation carrier cell lines and extend lifespan in CGG repeat-expressing Drosophila. These findings support a disease model whereby the CGG repeat expansion in FXTAS promotes chromatin remodeling in cis, which in turn increases expression of the toxic FMR1 mRNA. Moreover, these results provide proof of principle that HAT inhibitors or HDAC activators might be used to selectively repress transcription at the FMR1 locus.open293

The importance of the cellular stress response in the pathogenesis and treatment of type 2 diabetes

Organisms have evolved to survive rigorous environments and are not prepared to thrive in a world of caloric excess and sedentary behavior. A realization that physical exercise (or lack of it) plays a pivotal role in both the pathogenesis and therapy of type 2 diabetes mellitus (t2DM) has led to the provocative concept of therapeutic exercise mimetics. A decade ago, we attempted to simulate the beneficial effects of exercise by treating t2DM patients with 3 weeks of daily hyperthermia, induced by hot tub immersion. The short-term intervention had remarkable success, with a 1 % drop in HbA1, a trend toward weight loss, and improvement in diabetic neuropathic symptoms. An explanation for the beneficial effects of exercise and hyperthermia centers upon their ability to induce the cellular stress response (the heat shock response) and restore cellular homeostasis. Impaired stress response precedes major metabolic defects associated with t2DM and may be a near seminal event in the pathogenesis of the disease, tipping the balance from health into disease. Heat shock protein inducers share metabolic pathways associated with exercise with activation of AMPK, PGC1-a, and sirtuins. Diabetic therapies that induce the stress response, whether via heat, bioactive compounds, or genetic manipulation, improve or prevent all of the morbidities and comorbidities associated with the disease. The agents reduce insulin resistance, inflammatory cytokines, visceral adiposity, and body weight while increasing mitochondrial activity, normalizing membrane structure and lipid composition, and preserving organ function. Therapies restoring the stress response can re-tip the balance from disease into health and address the multifaceted defects associated with the disease