Carbofuran accelerates the cellular senescence and declines the life span of spns1 mutant zebrafish

Carbofuran is a carbamate pesticide, widely used in agricultural practices to increase crop productivity. In mammals, carbofuran is known to cause several untoward effects, such as apoptosis in the hippocampal neuron, oxidative stress, loss of memory and chromosomal anomalies. Most of these effects are implicated with cellular senescence. Therefore, the present study aimed to determine the effect of carbofuran on cellular senescence and biological ageing. Spinster homolog 1 (Spns1) is a transmembrane transporter, regulates autolysosomal biogenesis and plays a role in cellular senescence and survival. Using senescence-associated β-galactosidase staining, we found that carbofuran accelerates the cellular senescence in spns1 mutant zebrafish. The yolk opaqueness, a premature ageing phenotype in zebrafish embryos, was accelerated by carbofuran treatment. In the survival study, carbofuran shortened the life span of spns1 mutant zebrafish. Autophagy is the cellular lysosomal degradation, usually up-regulated in the senescent cells. To know the impact of carbofuran exposure on autophagy progress, we established a double-transgenic zebrafish line, harbouring EGFP-tagged LC3-II and mCherry-tagged Lamp1 on spns1 mutant background, whereas we found, carbofuran exposure synergistically accelerates autolysosome formation with insufficient lysosome-mediated degradation. Our data collectively suggest that carbofuran exposure synergistically accelerates the cellular senescence and affects biological ageing in spns1 defective animals.     

Evaluation of the effect of different concentrations of organic amendments and botanical extracts on the mortality and hatching of Meloidogyne javanica

Organic amendments and botanical extracts are considered as some of the eco-friendly alternatives to chemical pesticide in suppressing plant pathogenic nematodes (PPN). Root-knot nematode (RKN) is the most important group of PPN distributed globally causing both qualitative and quantitative damage to many crops. Vermicompost and biogas digestate (BD) are two forms of organic amendments reported to have potential to limit RKN infestation. Likewise, marigold (Tagates spp.) and cabbage (Brassica oleracea) are two widely studied botanicals having shown their potential to control RKN. However, there was not much in vitro research related to organic amendments and botanicals targeting a particular species of RKN to observe their nematicidal effect. An in vitro experiment was undertaken to evaluate the effect of these organic amendments and botanical extracts at different concentrations (10.0%, 25.0%, 50.0% and 100.0%) on the hatching and mortality of Meloidogyne javanica at different time spans. Mortality of J₂ and inhibition of hatching of egg mass of M. javanica differed significantly (p < 0.0001) among the interaction effect of treatments and incubation time for both organic amendments and botanical extracts. Findings of this experiment indicated that potentiality for increasing mortality and inhibition of hatching was higher and steadier in botanical extracts than those of organic amendments.     

Biological yields through agricultural extension activities and services: A case study from Al-Baha region – Kingdom of Saudi Arabia

PurposeThis research determines the extent to which farmers benefit from agricultural extension activities and services through realizing higher biological crop yields in the Al-Baha region of the Kingdom of Saudi Arabia. Additionally, the nature of the relationship between the personal, economic and social characteristics of farmers and the degree to which they benefit from agricultural extension activities and services are studied.MethodologyA simple random sample representing the community of 315 farmers was drawn. Data were collected through a personal interview with a pre-tested questionnaire to satisfy the objectives of the study. Data are subjected to analyses and are interpreted in terms of percentages, arithmetic averages, and standard deviations in addition to the simple Pearson correlation coefficients.ResultsThe results show that most of the respondents depend on personal experience, friends, family and neighbors, merchants and sellers of agricultural production supplies as sources of agricultural information for enhanced crop yields. Multiple regression analysis reveals that both the educational status and the agricultural information sources are important factors that increase farmers benefit from extension activities. Farmers receive most benefits from the extension activities and services from bringing in foreign workers, conducting field trips to farms, and identifying problems faced by farmers.Research limitations/implicationsThe outcome of this questionnaire limits generalization of the findings for other parts of the Kingdom due to geographical and natural resources variations.Practical implicationsThe personal and socio-economic characteristics of the surveyed population provide the extension service with insight into their composition – a basis to formulate workable extension programs. For the extension planners of the area, this effort provides a baseline study and may assist with targeting the appropriate farmers and catering the right solutions to the problems. Such a study will help devise meaningful extension programs and save time and resources.Originality/valueLittle previous research on the usefulness of the Extension Service has been conducted in the region.ConclusionsEffective, well-planned extension programs targeting the educated and mature farmers provided more benefits and helped them obtain higher crop yields.     

Wnt/β-catenin signaling pathway in uterine leiomyoma: role in tumor biology and targeting opportunities

Molecular and Cellular Biochemistry - Uterine leiomyoma is the most common tumor of the female reproductive system and originates from a single transformed myometrial smooth muscle cell. Despite...     

Receptor-based targeting of engineered nanocarrier against solid tumors: Recent progress and challenges ahead

BackgroundIn past few decades, the research on engineered nanocarriers (NCs) has gained significant attention in cancer therapy due to selective delivery of drug molecules on the diseased cells thereby preventing unwanted uptake into healthy cells to cause toxicity.Scope of reviewThe applicability of enhanced permeability and retention (EPR) effect for the delivery of nanomedicines in cancer therapy has gained limited success due to poor accessibility of the drugs to the target cells where non-specific payload delivery to the off target region lack substantial reward over the conventional therapeutic systems.Major conclusionsIn spite of the fact, nanomedicines fabricated from the biocompatible nanocarriers have reduced targeting potential for meaningful clinical benefits. However, over expression of receptors on the tumor cells provides opportunity to design functional nanomedicine to bind substantially and deliver therapeutics to the cells or tissues of interest by alleviating the bio-toxicity and unwanted effects. This critique will give insight into the over expressed receptor in various tumor and targeting potential of functional nanomedicine as new therapeutic avenues for effective treatment.General significanceThis review shortly shed light on EPR-based drug targeting using nanomedicinal strategies, their limitation, and advances in therapeutic targeting to the tumor cells.     

The fragility of a structurally diverse duplication block triggers recurrent genomic amplification

The human genome contains hundreds of large, structurally diverse blocks that are insufficiently represented in the reference genome and are thus not amenable to genomic analyses. Structural diversity in the human population suggests that these blocks are unstable in the germline; however, whether or not these blocks are also unstable in the cancer genome remains elusive. Here we report that the 500 kb block called KRTAP_region_1 (KRTAP-1) on 17q12–21 recurrently demarcates the amplicon of the ERBB2 (HER2) oncogene in breast tumors. KRTAP-1 carries numerous tandemly-duplicated segments that exhibit diversity within the human population. We evaluated the fragility of the block by cytogenetically measuring the distances between the flanking regions and found that spontaneous distance outliers (i.e DNA breaks) appear more frequently at KRTAP-1 than at the representative common fragile site (CFS) FRA16D. Unlike CFSs, KRTAP-1 is not sensitive to aphidicolin. The exonuclease activity of DNA repair protein Mre11 protects KRTAP-1 from breaks, whereas CtIP does not. Breaks at KRTAP-1 lead to the palindromic duplication of the ERBB2 locus and trigger Breakage-Fusion-Bridge cycles. Our results indicate that an insufficiently investigated area of the human genome is fragile and could play a crucial role in cancer genome evolution.     

Induction of HRR genes and inhibition of DNMT1 is associated with anthracycline anti-tumor antibiotic-tolerant breast carcinoma cells

Molecular and Cellular Biochemistry - The aim of the study was to understand the role of homologous recombination repair (HRR) pathway genes in development of chemotolerance in breast cancer (BC)....     

Identification of MAMDC1 as a Candidate Susceptibility Gene for Systemic Lupus Erythematosus (SLE)

Background

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with multiple susceptibility genes. We have previously reported suggestive linkage to the chromosomal region 14q21-q23 in Finnish SLE families.

Principal Findings

Genetic fine mapping of this region in the same family material, together with a large collection of parent affected trios from UK and two independent case-control cohorts from Finland and Sweden, indicated that a novel uncharacterized gene, MAMDC1 (MAM domain containing glycosylphosphatidylinositol anchor 2, also known as MDGA2, MIM 611128), represents a putative susceptibility gene for SLE. In a combined analysis of the whole dataset, significant evidence of association was detected for the MAMDC1 intronic single nucleotide polymorphisms (SNP) rs961616 (P –value = 0.001, Odds Ratio (OR) = 1.292, 95% CI 1.103–1.513) and rs2297926 (P –value = 0.003, OR = 1.349, 95% CI 1.109–1.640). By Northern blot, real-time PCR (qRT-PCR) and immunohistochemical (IHC) analyses, we show that MAMDC1 is expressed in several tissues and cell types, and that the corresponding mRNA is up-regulated by the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in THP-1 monocytes. Based on its homology to known proteins with similar structure, MAMDC1 appears to be a novel member of the adhesion molecules of the immunoglobulin superfamily (IgCAM), which is involved in cell adhesion, migration, and recruitment to inflammatory sites. Remarkably, some IgCAMs have been shown to interact with ITGAM, the product of another SLE susceptibility gene recently discovered in two independent genome wide association (GWA) scans.

Significance

Further studies focused on MAMDC1 and other molecules involved in these pathways might thus provide new insight into the pathogenesis of SLE.     

Association of eNOS gene intron 4 a/b VNTR polymorphisms in children with nephrotic syndrome

To investigate the association of endothelial nitric oxide synthase gene intron 4 (eNOS4) polymorphisms with nephrotic syndrome, the eNOS4 genotypes were assessed in 161 children with nephrotic syndrome in comparison with 78 healthy subjects. We classified the children with nephritic syndrome into 2 groups: as steroid-sensitive nephrotic syndrome (SSNS) (n = 125) and steroid-resistant nephrotic syndrome (SRNS) (n = 36). The eNOS4 polymorphisms were analyzed by polymerase chain reaction. The frequencies of eNOS4 aa, ab and bb genotypes were 3%, 31%, and 66% in all the nephrotic syndrome groups, and 1%, 23%, and 76% in the control group (x² = 2.87, p > 0.05). In addition, the frequencies of eNOS4 aa, ab and bb genotypes were 2%, 33%, and 65% in SSNS group, and 5%, 28%, and 67% in the SRNS group (x² = 1.13, p = 0.567). The present study is the first to investigate eNOS4 gene polymorphisms in children with SSNS and SRNS. Our data show that the eNOS4 gene polymorphisms were not associated with the development, frequent relapse and response to steroid in nephritic syndrome.