In silico Prediction of MicroRNAs in Plant Mitochondria

MicroRNAs are endogenous, short (ca. 21 base), non-coding, post transcriptional, regulatory RNA molecules. These microRNAs (miRNAs) are complementary to their target messenger RNAs, and bind principally to its 3' UTR. The conserved nature of miRNAs, and their high sequence complementarities of miRNA and its targets in plants, provides the basis for the easy identification of miRNA and its targets. Presence of miRNA in plant mitochondria is scantily studied. Identification of miRNA targets in plant mitochondria might indicate the involvement of miRNA in mitochondrial gene regulation and nuclear mitochondrial interactions. In this study, we used a computational approach to predict miRNA targets in plant mitochondria. The mitochondrial gene targets identified for miRNAs are located both in mitochondrial and nuclear compartments. This observation points to a fairly early origin of miRNAs. Besides, most of the targets identified can have copies in two compartments and suggest the possibility of miRNA mediated regulation. This study unfurls the possibility of regulating the plant mitochondrial genes by amending the miRNA genes in the nuclear compartment

SIRT3 and cancer: Tumor promoter or suppressor?

AbstractSirtuins (SIRT1–7), the mammalian homologues of the Sir2 gene in yeast, have emerging roles in age-related diseases, such as cardiac hypertrophy, diabetes, obesity, and cancer. However, the role of several sirtuin family members, including SIRT1 and SIRT3, in cancer has been controversial. The aim of this review is to explore and discuss the seemingly dichotomous role of SIRT3 in cancer biology with particular emphasis on its potential role as a tumor promoter and tumor suppressor. This review will also discuss the potential role of SIRT3 as a novel therapeutic target to treat cancer

Nisin, an apoptogenic bacteriocin and food preservative, attenuates HNSCC tumorigenesis via CHAC 1

Nisin, a bacteriocin and commonly used food preservative, may serve as a novel potential therapeutic for treating head and neck squamous cell carcinoma ( HNSCC ), as it induces preferential apoptosis, cell cycle arrest, and reduces cell proliferation in HNSCC cells, compared with primary keratinocytes. Nisin also reduces HNSCC tumorigenesis in vivo. Mechanistically, nisin exerts these effects on HNSCC , in part, through CHAC 1, a proapoptotic cation transport regulator, and through a concomitant CHAC 1‐independent influx of extracellular calcium. In addition, although CHAC 1 is known as an apoptotic mediator, its effects on cancer cell apoptosis have not been examined. Our studies are the first to report CHAC 1's new role in promoting cancer cell apoptosis under nisin treatment. These data support the concept that nisin decreases HNSCC tumorigenesis in vitro and in vivo by inducing increased cell apoptosis and decreased cell proliferation; effects that are mediated by activation of CHAC 1, increased calcium influxes, and induction of cell cycle arrest. These findings support the use of nisin as a potentially novel therapeutic for HNSCC , and as nisin is safe for human consumption and currently used in food preservation, its translation into a clinical setting may be facilitated. Nisin decreases HNSCC tumorigenesis in vitro and in vivo by inducing increased cell apoptosis and decreased cell proliferation; effects that are mediated by activation of CHAC1, increased calcium influxes, and induction of cell cycle arrest. These findings support the use of nisin as a potentially novel therapeutic for HNSCC , and as nisin is safe for human consumption and currently used in food preservation, its translation into a clinical setting may be facilitated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94527/1/cam435.pd

Polymicrobial periodontal disease triggers a wide radius of effect and unique virome.

Periodontal disease is a microbially-mediated inflammatory disease of tooth-supporting tissues that leads to bone and tissue loss around teeth. Although bacterially-mediated mechanisms of alveolar bone destruction have been widely studied, the effects of a polymicrobial infection on the periodontal ligament and microbiome/virome have not been well explored. Therefore, the current investigation introduced a new mouse model of periodontal disease to examine the effects of a polymicrobial infection on periodontal ligament (PDL) properties, changes in bone loss, the host immune response, and the microbiome/virome using shotgun sequencing. Periodontal pathogens, namely Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Fusobacterium nucleatum were used as the polymicrobial oral inoculum in BALB/cByJ mice. The polymicrobial infection triggered significant alveolar bone loss, a heightened antibody response, an elevated cytokine immune response, a significant shift in viral diversity and virome composition, and a widening of the PDL space; the latter two findings have not been previously reported in periodontal disease models. Changes in the PDL space were present at sites far away from the site of insult, indicating that the polymicrobial radius of effect extends beyond the bone loss areas and site of initial infection and wider than previously appreciated. Associations were found between bone loss, specific viral and bacterial species, immune genes, and PDL space changes. These findings may have significant implications for the pathogenesis of periodontal disease and biomechanical properties of the periodontium. This new polymicrobial mouse model of periodontal disease in a common mouse strain is useful for evaluating the features of periodontal disease

Apaf-1 overexpression partially overcomes apoptotic resistance in a cisplatin-selected HeLa cell line

AbstractInhibition of caspase-3-mediated apoptosis has been hypothesized to be associated with chemoresistance. Investigations of apoptosis revealed that cytosolic cytochrome c is associated with a complex of apoptotic protease activating factor-1 (Apaf-1), an adapter molecule, and caspase-9 to activate caspase-3. However, whether these apoptotic molecules are involved in acquired cisplatin resistance is not understood. The present work shows reduced activation of caspase-3 and apoptosis in a cisplatin-selected HeLa cell line. Ac-DEVD-CHO, a caspase-3 inhibitor, inhibited cisplatin-induced apoptosis about 60–70% in both cell lines. Ac-LEHD-CHO, a caspase-9 inhibitor or Ac-IETD-CHO, a caspase-8 inhibitor, inhibited cisplatin-induced caspase-3 activation and apoptosis similarly in both cell lines. In addition, cisplatin induced the activation of caspase-9, the upstream activator of caspase-3, in a dose-dependent manner, and the activation of caspase-9 was less induced in resistant cells. The accumulation of cytosolic cytochrome c, an activator of caspase-9, and the induction of the mitochondrial membrane-associated voltage-dependent anion channel were also reduced in cisplatin-resistant cells. However, the concentration of Bcl-2 family proteins in cisplatin-resistant cells was normal. The concentration of Apaf-1 was unaltered in both cell lines. Increasing the cellular concentration of Apaf-1 through the transient expression of the gene increased the induction of apoptosis in resistant cells, associated with enhanced activation of caspase-9, caspase-3 and DNA fragmentation factor. Regression analysis reveals that the modification factor, the ratio of the slope in the linear range of the dose–response curve with Apaf-1 to the slope without Apaf-1, is 1.5 and 4.75 in the HeLa and cisplatin-resistant HeLa cells, respectively. These results indicate that apoptosis and caspases are less induced in cisplatin-selected HeLa cells. They also suggest that ectopic overexpression of Apaf-1 may partially reverse the acquired cisplatin resistance

Principal Component Artificial Neural Network Calibration Models for Simultaneous Spectrophotometric Estimation of Phenobarbitone and Phenytoin Sodium in Tablets

Simultaneous estimation of all drug components in a multicomponent pharmaceutical dosage form with artificial neural networks calibration models using UV spectrophotometry has been reported as a simple alternative to using separate models for each component. A novel approach for calibration using computed spectral dataset derived from three spectra of each component has been described. Spectra of Phenobarbitone and Phenytoin sodium were recorded at several concentrations within their linear range and used to compute the calibration mixture between wavelengths 220 to 260 nm at an interval of 1 nm. Principal component back-propagation neural networks trained by Levenberg-Marquardt algorithm were used for building and optimizing calibration models using MATLAB ® Neural Network Toolbox. Neural network models were compared to principal component regression model. The calibration model was thoroughly evaluated at several concentration levels using spectra obtained for 95 synthetic binary mixtures prepared using orthogonal designs. The optimized model showed sufficient robustness even when the calibration sets were constructed from different set of pure spectra of components. Although the components showed significant spectral overlap, the model could accurately estimate the drugs, with satisfactory precision and accuracy, in tablet dosage with no interference from excipients as indicated by the recovery study results

Predicting alcohol-related memory problems in older adults: A machine learning study with multi-domain features

Memory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50-81 years) with alcohol-induced memory problems (the memory group) were compared with a matched control group who did not have memory problems. The random forests model identified specific features from each domain that contributed to the classification of the memory group vs. the control group (AUC = 88.29%). Specifically, individuals from the memory group manifested a predominant pattern of hyperconnectivity across the default mode network regions except for some connections involving the anterior cingulate cortex, which were predominantly hypoconnected. Other significant contributing features were: (i) polygenic risk scores for AUD, (ii) alcohol consumption and related health consequences during the past five years, such as health problems, past negative experiences, withdrawal symptoms, and the largest number of drinks in a day during the past twelve months, and (iii) elevated neuroticism and increased harm avoidance, and fewer positive uplift life events. At the neural systems level, hyperconnectivity across the default mode network regions, including the connections across the hippocampal hub regions, in individuals with memory problems may indicate dysregulation in neural information processing. Overall, the study outlines the importance of utilizing multidomain features, consisting of resting-state brain connectivity data collected ~18 years ago, together with personality, life experiences, polygenic risk, and alcohol consumption and related consequences, to predict the alcohol-related memory problems that arise in later life

Gender modulates the development of Theta Event Related Oscillations in Adolescents and Young Adults.

The developmental trajectories of theta band (4-7 Hz) event-related oscillations (EROs), a key neurophysiological constituent of the P3 response, were assessed in 2170 adolescents and young adults ages 12 to 25. The theta EROs occurring in the P3 response, important indicators of neurocognitive function, were elicited during the evaluation of task-relevant target stimuli in visual and auditory oddball tasks. These tasks call upon attentional and working memory resources. Large differences in developmental rates between males and females were found; scalp location and task modality (visual or auditory) differences within males and females were small compared to gender differences. Trajectories of interregional and intermodal correlations between ERO power values exhibited increases with age in both genders, but showed a divergence in development between auditory and visual systems during ages 16 to 21. These results are consistent with previous electrophysiological and imaging studies and provide additional temporal detail about the development of neurophysiological indices of cognitive activity. Since measures of the P3 response has been found to be a useful endophenotypes for the study of a number of clinical and behavioral disorders, studies of its development in adolescents and young adults may illuminate neurophysiological factors contributing to the onset of these conditions