Electroconductive materials as biomimetic platforms for tissue regeneration

In many diseases, tissue regeneration is compromised and/or insufficient to restore tissue/organ function. Therefore, novel regenerative therapies are being developed to enhance resident and transplanted cell proliferation and functional differentiation. Numerous biomaterials engineered to include nanocomponents have emerged as promising candidates to fulfil the need of mimicking the properties of the healthy extracellular matrix. This is particularly important for tissues that require electroconductive support to achieve optimal cellular function, such as muscles and neurons. In this review, we summarize and discuss the current state-of-the-art for electroconductive materials in tissue regeneration, with particular emphasis on materials containing nanocomponents.     

Metformin relieves neuropathic pain after spinal nerve ligation via autophagy flux stimulation

Neuropathic pain is a well‐known type of chronic pain caused by damage to the nervous system. Autophagy is involved in the development and/or progression of many diseases, including neuropathic pain. Emerging evidence suggests that metformin relieves neuropathic pain in several neuropathic pain models; however, metformin's cellular and molecular mechanism for pain relief remains unknown. In this study, we investigated the therapeutic effects of metformin on pain relief after spinal nerve ligation (SNL) and its underlying mechanism of autophagy regulation. Behavioural analysis, histological assessment, expression of c‐Fos and molecular biological changes, as well as ultrastructural features, were investigated. Our findings showed that the number of autophagosomes and expression of autophagy markers, such as LC3 and beclin1, were increased, while the autophagy substrate protein p62, as well as the ubiquitinated proteins, were accumulated in the ipsilateral spinal cord. However, metformin enhanced the expression of autophagy markers, while it abrogated the abundance of p62 and ubiquitinated proteins. Blockage of autophagy flux by chloroquine partially abolished the apoptosis inhibition and analgesic effects of metformin on SNL. Taken together, these results illustrated that metformin relieved neuropathic pain through autophagy flux stimulation and provided a new direction for metformin drug development to treat neuropathic pain.     

Evaluating Land Use Dynamics and Forest Cover Change in Nepal’s Bara District (1973–2003)

This research uses Landsat Multi-Spectral Scanner of 1973, Thematic Mapper of 1989, Advance Earth Observing Satellite of 1996, and Enhanced Thematic Mapper of 2003 imagery to examine the effects of socioeconomic and demographic factors on land use and forest cover dynamics in the Bara district of the Central Tarai Region of Nepal for 1973–2003. These satellite images are used to generate three transition matrices for 1973–1989, 1989–1996, and 1996–2003; and the outcomes of the final transition matrix are compared with the land use and cover patterns seen on the IKONOS (1 × 1 m) 2003 images. This paper contributes to our understanding of how land use and cover dynamics correspond to national-level socioeconomic developments, demographic changes, and environmental awareness as envisioned by Ecological Modernization Theory. It also demonstrates how such a set of transition matrices generated from different resolution images helps assess these explanatory relationships at different temporal and spatial scales.     

Arsenic-induced health effects and genetic damage in keratotic individuals: involvement of p53 arginine variant and chromosomal aberrations in arsenic susceptibility

In West Bengal, India, more than 6 million people are exposed to arsenic through drinking water. Chronic arsenic exposure results in several multisystemic non-cancerous as well as cancerous effects in humans. Among non-cancerous effects, arsenic-specific skin lesions, conjunctivitis, peripheral neuropathy and respiratory diseases are prominent. One of the major consequences of chronic arsenic exposure is keratosis, the precancerous state of skin cancer. The tumor suppressor protein p53 consists of a polymorphism proline72arginine reported to be associated with various types of cancers. Previously we have reported that the p53 codon 72 arginine (Arg) homozygous genotype is associated with the development of arsenic-induced keratosis. In the present study we have investigated the distribution of health effects and chromosomal aberrations (CAs) in the individuals with keratosis. We have compared individuals with keratosis with those without arsenic-induced skin lesions but drinking similar level of arsenic-contaminated water. Attempts have also been made to find out the association of the p53 risk genotype with health effects and chromosomal aberrations. This study comprises of 349 unrelated exposed individuals (162 individuals with keratosis and 187 individuals without arsenic-specific skin lesions) from highly arsenic-affected districts of West Bengal, India. The results showed that health effects (i.e. peripheral neuropathy, conjunctivitis and respiratory illness) and chromosomal aberrations were significantly higher in the keratotic group compared to individuals with no skin lesions. Moreover, individuals with the arginine homozygous genotype showed increased levels of chromosomal aberrations compared to individuals with other genotypes; however, we did not find any significant association of the risk genotype with health effects. This study suggests that individuals with keratosis are more susceptible to arsenic-induced health effects and genetic damage and that the arginine variant of p53 can further influence the repair capacity of arsenic-exposed individuals, leading to increased accumulation of chromosomal aberrations.     

Designing constructed wetlands for reclamation of pretreated wastewater and stormwater

Wastewater reclamation is getting greater attention as an alternative to conventional approaches to wastewater treatment and water supply due to increasing water stress coupled with more stringent water quality limitation for discharge of treated wastewater. Among the few technologies adopted in the field for wastewater reclamation, constructed wetlands have been used to reclaim both primary and secondary treated wastewater in regions with arid and humid climates. This paper summarizes the widely adopted guidelines that need to be considered when designing constructed wetlands for wastewater reclamation, discusses the capacity of wetland treatment systems for water reuse while assessing the status of full-scale constructed wetlands designed for wastewater reclamation, and develops contaminant loading charts as a design tool based on the performance of existing full-scale constructed wetlands deployed for wastewater reclamation. It is evident that constructed wetland systems provide a viable means to treat wastewater to the levels required for low-quality reuses such as restricted irrigation and impoundment. It is challenging for constructed wetlands to consistently meet microbiological guidelines for high-quality reuses such as unrestricted agricultural and urban reuses. Wastewater reclaimed through constructed wetlands is used mainly for agricultural and landscape irrigation, groundwater recharge, indirect potable reuse, and environmental reuse. Surface area and hydraulic loading rate of constructed wetlands to be deployed for wastewater reclamation can be estimated with contaminant loading charts derived from monitoring data of existing full-scale operations.     

The first draft of the pigeonpea genome sequence

Pigeonpea (Cajanus cajan) is an important grain legume of the Indian subcontinent, South-East Asia and East Africa. More than eighty five percent of the world pigeonpea is produced and consumed in India where it is a key crop for food and nutritional security of the people. Here we present the first draft of the genome sequence of a popular pigeonpea variety ??Asha??. The genome was assembled using long sequence reads of 454 GS-FLX sequencing chemistry with mean read lengths of >550?bp and >10-fold genome coverage, resulting in 510,809,477?bp of high quality sequence. Total 47,004 protein coding genes and 12,511 transposable elements related genes were predicted. We identified 1,213 disease resistance/defense response genes and 152 abiotic stress tolerance genes in the pigeonpea genome that make it a hardy crop. In comparison to soybean, pigeonpea has relatively fewer number of genes for lipid biosynthesis and larger number of genes for cellulose synthesis. The sequence contigs were arranged in to 59,681 scaffolds, which were anchored to eleven chromosomes of pigeonpea with 347 genic-SNP markers of an intra-species reference genetic map. Eleven pigeonpea chromosomes showed low but significant synteny with the twenty chromosomes of soybean. The genome sequence was used to identify large number of hypervariable ??Arhar?? simple sequence repeat (HASSR) markers, 437 of which were experimentally validated for PCR amplification and high rate of polymorphism among pigeonpea varieties. These markers will be useful for fingerprinting and diversity analysis of pigeonpea germplasm and molecular breeding applications. This is the first plant genome sequence completed entirely through a network of Indian institutions led by the Indian Council of Agricultural Research and provides a valuable resource for the pigeonpea variety improvement.     

Mitochondrial DNA Polymerase POLG1 Disease Mutations and Germline Variants Promote Tumorigenic Properties

Germline mutations in mitochondrial DNA polymerase gamma (POLG1) induce mitochondrial DNA (mtDNA) mutations, depletion, and decrease oxidative phosphorylation. Earlier, we identified somatic mutations in POLG1 and the contribution of these mutations in human cancer. However, a role for germline variations in POLG1 in human cancers is unknown. In this study, we examined a role for disease associated germline variants of POLG1, POLG1 gene expression, copy number variation and regulation in human cancers. We analyzed the mutations, expression and copy number variation in POLG1 in several cancer databases and validated the analyses in primary breast tumors and breast cancer cell lines. We discovered 5-aza-2''-deoxycytidine led epigenetic regulation of POLG1, mtDNA-encoded genes and increased mitochondrial respiration. We conducted comprehensive race based bioinformatics analyses of POLG1 gene in more than 33,000 European-Americans and 5,000 African-Americans. We identified a mitochondrial disease causing missense variation in polymerase domain of POLG1 protein at amino acid 1143 (E1143G) to be 25 times more prevalent in European-Americans (allele frequency 0.03777) when compared to African-American (allele frequency 0.00151) population. We identified T251I and P587L missense variations in exonuclease and linker region of POLG1 also to be more prevalent in European-Americans. Expression of these variants increased glucose consumption, decreased ATP production and increased matrigel invasion. Interestingly, conditional expression of these variants revealed that matrigel invasion properties conferred by these germline variants were reversible suggesting a role of epigenetic regulators. Indeed, we identified a set of miRNA whose expression was reversible after variant expression was turned off. Together, our studies demonstrate altered genetic and epigenetic regulation of POLG1 in human cancers and suggest a role for POLG1 germline variants in promoting tumorigenic properties.     

ErmineJ: Tool for functional analysis of gene expression data sets

Background  

It is common for the results of a microarray study to be analyzed in the context of biologically-motivated groups of genes such as pathways or Gene Ontology categories. The most common method for such analysis uses the hypergeometric distribution (or a related technique) to look for "over-representation" of groups among genes selected as being differentially expressed or otherwise of interest based on a gene-by-gene analysis. However, this method suffers from some limitations, and biologist-friendly tools that implement alternatives have not been reported.