Cumulative mtDNA damage occurs in aging animals, and mtDNA mutations are reported to accelerate aging in mice. We determined whether aging results in increased DNA oxidative damage and reduced mtDNA abundance and mitochondrial function in skeletal muscle of human subjects. Studies performed in 146 healthy men and women aged 18 -89 yr demonstrated that mtDNA and mRNA abundance and mitochondrial ATP production all declined with advancing age. Abundance of mtDNA was positively related to mitochondrial ATP production rate, which in turn, was closely associated with aerobic capacity and glucose tolerance. The content of several mitochondrial proteins was reduced in older muscles, whereas the level of the oxidative DNA lesion, 8-oxo-deoxyguanosine, was increased, supporting the oxidative damage theory of aging. These results demonstrate that age-related muscle mitochondrial dysfunction is related to reduced mtDNA and muscle functional changes that are common in the elderly.sarcopenia ͉ mtDNA ͉ oxidative damage ͉ mRNA ͉ mitochondrial proteins M any structural and functional changes occur with age in skeletal muscle in a wide range of species. In Caenorhabditis elegans, muscle changes resembling those in humans precede neuronal changes, and are a determinant of morbidity (1). Age-related muscle wasting, muscle weakness, and reduced aerobic capacity result in many metabolic disorders and diminished physical performance in humans (2-4). Reduced muscle mitochondrial function could contribute to age-related muscle dysfunction and reduced aerobic capacity. Increased prevalence of mtDNA mutations (5, 6) and decreased mtDNA abundance (7, 8) have been proposed as underlying causes of mitochondrial dysfunction in aging. This finding is based on a hypothesis that cumulative oxidative damage could be the cause of aging (9).The rate of synthesis of contractile and mitochondrial proteins in human skeletal muscle declines with advancing age and may alter muscle metabolic capacity in older people (2-4). The activity of oxidative enzymes and content mRNA transcripts encoding mitochondrial proteins are also reduced in older muscles (3,7,10,11). Reduced synthesis and activity of specific proteins can alter muscle functions. The major functional role of mitochondria is ATP generation, but it remains unclear whether mitochondrial ATP production rate (MAPR) in skeletal muscle declines with age in humans. Previous studies that attempted to address this question are not in agreement, reporting that MAPR is either unchanged with age (12-16) or declines (17-19). These differences may arise from the use in some studies of inadequate sample sizes, failure to account for wide variations in physical fitness and diet, and the inclusion of subjects with metabolic abnormalities or undergoing surgical procedures at the time of analysis. Most of the previous studies examined discrete groups of younger and older people so it is unclear whether changes in mitochondria occur continuously across the adult life span or arise more rapidly later in life. We th...

Words and phrases bespeak the perspectives of people about products, services, governments and events on social media. Extricating positive or negative polarities from social media text denominates task of sentiment analysis in the field of natural language processing. The exponential growth of demands for business organizations and governments, impel researchers to accomplish their research in sentiment analysis. This paper leverages four state-of-the-art machine learning classifiers viz. Naïve Bayes, J48, BFTree and OneR for optimization of sentiment analysis. The experiments are performed using three manually compiled datasets; two of them are captured from Amazon and one dataset is assembled from IMDB movie reviews. The efficacies of these four classification techniques are examined and compared. The Naïve Bayes found to be quite fast in learning whereas OneR seems more promising in generating the accuracy of 91.3% in precision, 97% in F-measure and 92.34% in correctly classified instances.

Photostable and inherently luminescent biocompatible nanomaterials have tremendous importance in biomedical research. Herein, we have designed a pH-responsive inherently luminescent carbon dot (CD)-based coacervate nanodroplet (ND) in the presence of cationic polymer poly­(diallyldimethyl­ammonium chloride) (PDADMAC). The physicochemical and photoluminescence (PL) properties of these NDs have been explored as a function of equilibration time (1 and 18 h), pH (2–12), and ionic strength (1–1000 mM NaCl) by using various spectroscopic and microscopic techniques. Equilibrating the binary mixture of CD and PDADMAC for 1 and 18 h results in the formation of smaller (73.0 ± 2.3 nm) and larger sized (∼400 nm) NDs (SNDs and LNDs), respectively. While these NDs are stable in a broad pH range (5–12) and low ionic strength (<200 mM) medium, they disassembled in lower acidic pH (<5.5) and a high ionic strength (>200 mM) medium. Using UV–vis and confocal laser scanning microscopy, we have demonstrated that these negatively charged (ζ-potential = −17.0 ± 0.5 mV) NDs can spontaneously sequester neutral, cationic, and anionic dyes inside their porous nanostructure without any aggregation or structural disruption. In addition, a high partition coefficient of 10.6 ± 1.1 has been estimated for the cationic anticancer drug doxorubicin toward these NDs. The cell viability assay of SNDs with kidney fibroblast cell lines (BHK-21) reveals excellent biocompatibility. Finally, the bare and ethidium bromide (EtBr)-loaded SNDs have been utilized toward time-dependent cellular uptake experiments. Our findings indicate that the internalized SNDs undergo disassembly at lower acidic pH of late endosomes/lysosomes. While released EtBr in the cytosol specifically bind with nucleic acid within the cell nucleus without losing their affinity, free CDs on the other hand stain the whole cell without any specificity. Taken together, our present findings highlight the potential of these biocompatible inherently luminescent pH-responsive NDs toward theranostic applications.

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Stimuli-responsive water-dispersible and structurally robust nanoassemblies find tremendous importance in the biomedical domain for delivery of therapeutically active hydrophobic drugs and bioimaging applications. Herein we have demonstrated the loading of a hydrophobic model anticancer drug, [(p-cymene)Ru(curcuminato)-Cl] (Ru-Cur), inside hydrophobic compartments of different nanoassemblies, namely, micelles, liposomes, and coacervate nanodroplets, and studied the in vitro pH-and temperature-dependent controlled-release profiles. In the present study, both carbon-dot and adenosine triphosphate (ATP)-based coacervate nanodroplets have been fabricated in the presence of poly(diallyldimethylammonium chloride) (PDADMAC). It has been observed that the coacervate nanodroplets provide an ideal microenvironment for efficient loading (loading content = 31.2%, and encapsulation efficiency = 99.6%) and sustained release of the hydrophobic drug. The tailorability in the structure and physicochemical properties of coacervate nanodroplets along with high drug loading and negligible drug leakage at physiological conditions makes them ideal nanocarriers over other conventional nanoassemblies. Experimental release profiles for Ru-Cur-loaded ATP nanodroplets at different pH values fit well with a semiempirical power law model. The fitted parameters reveal diffusion-and swelling-controlled-release mechanism in the pH range between 7.4 and 6 and diffusion-and erosion-controlled-release mechanism at pH 5. Moreover, it has been found that the temperature has a profound influence on the drug-release profiles. The present study provides fundamental insight into the pHresponsive disassembly mechanism and highlights the potential importance of these Ru-Cur-loaded coacervates toward various theranostic applications.

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A series of isonicotinoyl hydrazones have been synthesized via template method and were complexed to Cu(II). The ligands are coordinated to Cu(II) ion through the enolic oxygen and azomethine nitrogen resulting in a square planar geometry. The CT-DNA and bovine serum albumin binding propensities of the compounds were determined spectrophotometrically, the results of which indicate good binding propensity of complexes to DNA and BSA with high binding constant values. Furthermore, the compounds have been investigated for their cytotoxicities on A549 human lung cancer cell. Also the mode of cell death was examined employing various staining techniques and was found to be apoptotic.

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