Evaluating Differential Gene Expression Using RNA-Sequencing: A Case Study in Diet-Induced Mouse Model Associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and CXCL12-Vs- TGFβ Induced Fibroblast to Myofibroblast Phenoconversion

Unlike the genome, cell transcriptome is dynamic and specific for a given cell developmental stage. Transcriptomics study is crucial to understand the functional elements of the genome to divulge molecular constituents of cells. The recent development of high-throughput sequencing technologies has provided an unprecedented method to sequence RNA and it has been emerging as the preferred technology for both characterization and quantification of the cell transcripts. Using “Tailor_Pipeline” we have analyzed diet-induced mouse and stromal fibroblast RNA-Seq samples and deciphers the differentially expressed genes that were significantly up- and downregulated and associated with several metabolic immune responses that presumably associated with liver disease. Analyzing the diet-induced mice model allowed us to encapsulate the transcriptional differences between diet-induced mice that can aid in the understanding of NAFLD and consequent liver pathogenesis. Identification of genes downregulated in metabolic processes and upregulated in immune responses indicate that mice model exhibiting liver disease. Moreover, the finding of a premalignant signature suggests that NAFLD may begin to progress towards hepatocellular carcinoma much earlier than earlier consideration. Tissue fibrosis arises due to overgrowth, scarring of various tissues and is attributed to deposition of the extracellular matrix including collagen, influenced by the actions of several pro-fibrotic proteins that can induce myofibroblast phenoconversion. Though recent transcriptomics analysis reveals the cellular identity, its ability to provide biologically meaningful insights in fibrosis is largely unexplored. To unravel the mechanisms at the genetic level, we have considered TGFβ/TGFβR and CXCL12/CXCR4 transcriptomes in human stromal fibroblasts. Transcriptome profiling technology revealed CXCL12/CXCR4 axis is responsible for the activation of COPII vesicle formation, ubiquitination, and Golgi/ER localization/targeting. Especially, identification of CUL3 and KLHL12 are responsible for the transportation of procollagen from ER to the Golgi. Interestingly, over-expression of CUL3 and KLHL12 are highly correlated with procollagen secretion by CXCL12-treated cells, but not in TGFβ-, treated cells. Moreover, this analysis showed how activation of the CXCL12/CXCR4 axis promotes procollagen I secretion that responsible for the deposition of ECM which is a characteristic of fibrosis

Life cycle assessment of solid waste management options: A Review

Evaluating the environmental performance of municipal solid waste management options is a complex job. LCA is an analytical tool (software) for assessing the environmental acceptability of municipal solid waste management (MSWM) options. LCA is currently being used in several countries to evaluate different strategies for integrated solid waste management and to evaluate treatment options for waste fractions. According to the characteristics of solid wastes, and availability of disposal options, LCA helps in supporting the identification of opportunities for pollution prevention and reductions in resource consumption while taking the entire solid waste life cycle. The primary elements of solid waste management are generation, collection, transportation, treatment, and disposal. Different scenarios were developed and reported as alternatives to the current waste management systems. The most prominent is material recovery facility (MRF) and other methods involve source reduction, reuse, recycling, composting, incineration, energy recovery, on-site burial, open burning and bioremediation. The goal of this review is to determine the most environmentally friendly option of MSWM system with the help of LCA

Kannan-type cyclic contraction results in 22-Menger space

summary:In this paper we establish Kannan-type cyclic contraction results in probabilistic 2-metric spaces. We use two different types of $t$-norm in our theorems. In our first theorem we use a Hadzic-type $t$-norm. We use the minimum $t$-norm in our second theorem. We prove our second theorem by different arguments than the first theorem. A control function is used in our second theorem. These results generalize some existing results in probabilistic 2-metric spaces. Our results are illustrated with an example

<em>Drosophila melanogaster</em>: A Robust Tool to Study Candidate Drug against Epidemic and Pandemic Diseases

Drosophila melanogaster is a widely used, dynamic model organism to study various pathogenic diseases observed ubiquitously in the human population. Drosophila, at present, is extensively used to conduct preclinical studies besides its counterpart rodents. The epidemic and pandemic diseases are discussed in this review to demonstrate Drosophila melanogaster as a key model. Epidemic and pandemic diseases are still claiming more than 5 million lives every year, and these diseases were well studied in flies. Currently there is no cure for the disease like HIV; the bacterial and fungal infections usually seen in HIV/AIDS patients could be demonstrated elaborately in Drosophila melanogaster. Diseases like myocardial infractions and cancer causing viral infection are long term effects of ART (anti-retroviral therapy) that could be experimented in flies. Stable Drosophila S2 cell line, Transgenic flies, transfusion of bacteria and fungi could be implemented to study several infectious diseases and for vaccine development. The latest trends in understanding pathogenic diseases and its potential biochemical markers in flies are discussed in this review to utilize the fruit flies as a functional tool and to explore further it in drug development. The advantages and disadvantages of the fly as a model of infection are discussed along with the epidemiology and the cellular pathophysiolog

Apigenin, a Bioactive Flavonoid from Lycopodium clavatum, Stimulates Nucleotide Excision Repair Genes to Protect Skin Keratinocytes from Ultraviolet B-Induced Reactive Oxygen Species and DNA Damage

AbstractIn this study, we examined the antioxidative and the DNA protective potentials of apigenin, a flavonoid polyphenol isolated from Lycopodium clavatum, in both in-vitro (HaCaT skin keratinocytes) and in-vivo (mice) models against UV-B radiation. We used DAPI staining in UV-B-irradiated HaCaT skin keratinocytes pre-treated with and without apigenin to assess DNA damage. We also used a flow-cytometric analysis in mice exposed to UV-B radiation with or without topical application of apigenin to assess, through a comet assay, chromosomal aberrations and quanta from reactive oxygen species (ROS) generation. Data from the stability curves for the Gibb's free energy determined from a melting-temperature profile study indicated that apigenin increased the stability of calf thymus DNA. Immunofluorescence studies revealed that apigenin caused a reduction in the number of cyclobutane pyrimidine dimers (CPDs) after 24 h, the time at which the nucleotide excision repair (NER) genes were activated. Thus, apigenin accelerated reversal of UV-B-induced CPDs through up-regulation of NER genes, removal of cyclobutane rings, inhibition of ROS generation, and down-regulation of NF-κB and MAPK, thereby revealing the precise mechanism of DNA repair

Preclinical Evaluation of Tropic Activity on Isolated Frog Heart by Using Volatile Oil of Nigella sativa Seeds

The lifestyle of people has changed over the time. Before the revolution days, people suffered from various diseases and the availability of medicines were not available. Today’s life is busier. Healthcare system has improved a lot but at the same time the number of people getting affected by different sources is still on a rise. The number one cause of death worldwide is due to heart diseases. The death rates due to cardiovascular disease increased. In order to improve the health conditions, there is a continuous development of synthetic and herbal medicines. Recently, rise in the use of herbal medicines have due to its natural origins and less side effects. One of the emerging herbs is Nigella sativa described as the remedy of all diseases. The tropic activity of the extracted volatile oil from Nigella sativa is observed on the isolated frog’s heart. The heart was isolated from the frog and was treated with adrenaline and acetylcholine to study its activity respectively. The isolated heart was also treated with the volatile oil of Nigella sativa seeds which produced dose dependent bradycardia like situation followed by cardiac arrest

Hypercube and Cascading-based Algorithms for Secret Sharing Schemes

Secret sharing is a very useful way to maintain secrecy of private data when stored in a distributed way among several nodes. Two significant questions in this area are 1. how to accommodate new nodes and assign shares to the new nodes, the problem becomes harder if the number of joining nodes or the access structure is not known in advance and can be (potentially) unbounded and 2. to reduce the computational complexity of secret sharing schemes. In this paper we propose two new constructions of such secret sharing schemes based on different combinatorial structures. The first construction is based on generalized paths joining the opposite vertices of a hypercube which has been divided into smaller hypercubes. The second construction is a forest- based construction utilizing a dynamic data structure technique known as fractional cascading. The generalized path we call a pavement is new to this paper. Both our constructions use a new secret redistribution scheme to assign and re-assign shares to nodes. Towards the second question we show that allowing certain trade-offs, the constructions are implementable by $AC^0$ circuits which is the lowest complexity class in which secret sharing and reconstruction is possible. To the best of the knowledge of the authors, none of the similar existing schemes (evolving or dynamic) are $AC^0$ computable and this paper for the first time combines the idea of hypercubes and dynamic data structures with secret sharing for preserving long-term confidentiality of secret data

Environmental toxicity influences disease spread in consumer population

The study of infectious disease has been of interest to ecologists since long. The initiation of epidemic and the long term disease dynamics are largely influenced by the nature of the underlying consumer (host)-resource dynamics. Ecological traits of such systems may be often modulated by toxins released in the environment due to ongoing anthropogenic activities. This, in addition to toxin-mediated alteration of epidemiological traits, has a significant impact on disease progression in ecosystems which is quite less studied. In order to address this, we consider a mathematical model of disease transmission in consumer population where multiple traits are affected by environmental toxins. Long term dynamics show that the level of environmental toxin determines disease persistence, and increasing toxin may even eradicate the disease in certain circumstances. Furthermore, our results demonstrate bistability between different ecosystem states and the possibility of an abrupt transition from disease-free coexistence to disease-induced extinction of consumers. Overall the results from this study will help us gain fundamental insights into disease propagation in natural ecosystems in the face of present anthropogenic changes

Risk of colorectal cancer in self-reported inflammatory bowel disease and modification of risk by statin and NSAID use

BACKGROUND: Statins and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced risk of colorectal cancer (CRC) in some studies. The objective of this study was to quantify the relative risk of inflammatory bowel disease (IBD) as a risk factor for CRC and to estimate whether this risk may be modified by long-term use of NSAIDs or statins. METHODS: The Molecular Epidemiology of Colorectal Cancer study is a population-based, case-control study of incident colorectal cancer in northern Israel and controls matched by age, sex, clinic, and ethnicity. Personal histories of IBD and medication use were measured by structured, in-person interview. The relative risk of IBD and effect modification by statins and NSAIDs were quantified by conditional and unconditional logistic regression. RESULTS: Among 1921 matched pairs of CRC cases and controls, a self-reported history of IBD was associated with a 1.9-fold increased risk of CRC (95% confidence interval [CI], 1.12-3.26). Long-term statin use was associated with a reduced risk of both IBD-associated CRC (odds ratio [OR] = 0.07; 95% CI, 0.01-0.78) and non-IBD CRC (OR = 0.49; 95% CI, 0.39-0.62). Stratified analysis suggested that statins may be more protective among those with IBD (ratio of OR = 0.14; 95% CI, 0.01-1.31; P = .51), although not statistically significant. NSAID use in patients with a history of IBD was suggestive of reduced risk of CRC but did not reach statistical significance (OR = 0.47; 95% CI, 0.12-1.86). CONCLUSIONS: The risk of CRC was elevated 1.9-fold in patients with IBD. Long-term statin use was associated with reduced risk of CRC in patients with IBD. Cancer 2011. © 2010 American Cancer Society.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84387/1/25731_ftp.pd

Understanding Pathophysiology of Sporadic Parkinson\u27s Disease in Drosophila Model: Potential Opportunities and Notable Limitations

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting approximately 1% of the population over age 50. PD is widely accepted as a multifactorial disease with both genetic and environmental contributions. Despite extensive research conducted in the area the precise etiological factors responsible remain elusive. In about 95% Parkinsonism is considered to have a sporadic component. There are currently no established curative, preventative, or disease-modifying interventions, stemming from a poor understanding of the molecular mechanisms of pathogenesis. Here lies the importance of animal models. Pharmacological insults cause Parkinsonian like phenotypes in Drosophila, thereby modelling sporadic PD. The pesticides paraquat and rotenone induced oxidative damage causing cluster specific DA neuron loss together with motor deficits. Studies in fly PD model have deciphered that signaling pathways such as phosphatidylinositol 3-kinase (PI3K/Akt and target of rapamycin (TOR), c-Jun N-terminal kinase (JNK) have been defective. Further, these studies have demonstrated that fruit fly can be a potential model to screen chemical compounds for their neuroprotective efficacy