Insights into mechanism of tumour promotion by mezerein

The objective of this study was to gather insights and compare the mode of action of the non phorbol, diterpene mezerein with the phorbol ester, phorbol-12-myristate-13 acetate, in normal and transformed cells. Both phorbol-12-myristate-13 acetate and mezerein are shown to activate the signal transduction pathways involving post translational modification of proteins by poly ADP-ribosylation and by protein kinase C, but to varying extents and showed different time kinetics and cell type differences. Multiple nuclear proteins, especially histones H3d, A24 and HI served as acceptors of poly ADP-ribose in response to PMA in both NIH 3T3 and HDCS cells whereas H1 and H2B were the major acceptors in case of mezerein treatment, similarly in both NIH 3T3 and HDCS cells. The results suggest an epigenetic mechanism (s) in tumour promotion by mezerein.     

Predatory and toxic effects of the turbellarian (Stenostomum cf leucops) on the population dynamics of Euchlanis dilatata,Plationus patulus (Rotifera) and Moina macrocopa (Cladocera)

Catenulid turbellarians, common in shallow, tropical ponds, affect their rotifer prey via the production of toxins. There is, however, no quantitative information on their effect on the demography of their prey. Here, we test the impact of Stenostomum cf leucops on the population dynamics of the rotifers Euchlanis dilatata and Plationus patulus, and the cladoceran Moina macrocopa. Experiments were initiated with rotifers at 0.5 ind. ml⁻¹ and the cladoceran at 0.2 ind. ml⁻¹; growth patterns were compared in the absence and presence of worms (2 Stenostomum ind. per 50 ml). Results revealed that brachionids were most adversely affected: there was a lower growth rate of the rotifers in the presence of worms (P < 0.01, repeated measures ANOVA), although at the densities applied, the predator did not wipe out its prey. These littoral predators may therefore regulate rotifer prey in natural conditions. In Moina, the population evolved differently; initially, we found no difference between control and treatment, but after about 10 days, the population collapsed, irrespective of a direct or indirect contact with the predator. This delayed effect deserves more study, as it could represent flatworm toxin accumulation by the cladoceran.     

A knowledgebase resource for interleukin-17 family mediated signaling

Interleukin-17 (IL-17) belongs to a relatively new family of cytokines that has garnered attention as the signature cytokine of Th17 cells. This cytokine family consists of 6 ligands, which bind to 5 receptor subtypes and induce downstream signaling. Although the receptors are ubiquitously expressed, cellular responses to ligands vary across tissues. The cytokine family is associated with various autoimmune disorders including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, asthma and psoriasis in addition to being implicated in the pathogenesis of cancer. In addition, this family plays a role in host defense against bacterial and fungal infections. The signaling mechanisms of the IL-17 family of proinflammatory cytokines are not well explored. In this study, we present a resource of literature-annotated reactions induced by IL-17. The reactions are catalogued under 5 categories, namely; molecular association, catalysis, transport, activation/inhibition and gene regulation. A total of 93 molecules and 122 reactions have been annotated. The IL-17 pathway is freely available through NetPath, a resource of signal transduction pathways previously developed by our group.     

PxdA interacts with the DipA phosphatase to regulate peroxisome hitchhiking on early endosomes

In canonical microtubule-based transport, adaptor proteins link cargoes to dynein and kinesin motors. Recently, an alternative mode of transport known as “hitchhiking” was discovered, where cargoes achieve motility by hitching a ride on already-motile cargoes, rather than attaching to a motor protein. Hitchhiking has been best studied in two filamentous fungi, Aspergillus nidulans and Ustilago maydis. In U. maydis, ribonucleoprotein complexes, peroxisomes, lipid droplets (LDs), and endoplasmic reticulum hitchhike on early endosomes (EEs). In A. nidulans, peroxisomes hitchhike using a putative molecular linker, peroxisome distribution mutant A (PxdA), which associates with EEs. However, whether other organelles use PxdA to hitchhike on EEs is unclear, as are the molecular mechanisms that regulate hitchhiking. Here we find that the proper distribution of LDs, mitochondria, and preautophagosomes do not require PxdA, suggesting that PxdA is a peroxisome-specific molecular linker. We identify two new pxdA alleles, including a point mutation (R2044P) that disrupts PxdA’s ability to associate with EEs and reduces peroxisome movement. We also identify a novel regulator of peroxisome hitchhiking, the phosphatase DipA. DipA colocalizes with EEs and its association with EEs relies on PxdA. Together, our data suggest that PxdA and the DipA phosphatase are specific regulators of peroxisome hitchhiking on EEs.     

Hyperphagia in offsprings of in utero hyperglycemic mothers is associated with increased expression of heparan sulfate proteoglycans in hypothalamus

In utero hyperglycemia has consequences on future outcomes in the offsprings. We had earlier shown that in utero hyperglycemia impacts proteoglycans/glycosaminoglycans, one of the key molecules involved in brain development. Hypothalamic HSPGs such as syndecan-1 and syndecan-3 are well known for their involvement in feeding behavior. Therefore, studies were carried out to determine the effect of maternal hyperglycemia on the expression of HSPGs in the hypothalamus of offspring brain. Results revealed increased protein abundance of Syndecan-1 and -3 as well as glypican-1 in postnatal adults from hyperglycemic mothers. This was associated with increased hyperphagia and increased expression of Neuropeptide Y. These results indicate the likely consequences on offsprings exposed to in utero hyperglycemia on its growth.

Graphical abstract

     

Endocrine disrupting effects,at different temperatures,on <Emphasis Type="Italic">Moina micrura</Emphasis> (Cladocera: Crustacea) induced by carbendazim,a fungicide

Pesticide-induced effects in non-target organisms are a worldwide environmental problem and cladocerans have been used as test organisms to quantify the toxicity effects. However, little is known about the true risks of acceptable levels, when non-traditional end points such as sex determination, egg maturation, and teratogenesis are considered. Aims of the present study were to investigate the effects of sublethal concentrations of the fungicide carbendazim taking into account the above-mentioned endpoints and to evaluate their sensitivity to an environmental factor such as temperature, known to influence growth rates and sex determination in cladocerans. We quantified the effect on the life history variables of Moina micrura at two different temperatures using the life table demographic approach, starting with neonates. The median lethal concentration of carbendazim for M. micrura was 0.12 ± 0.01 mg l⁻¹. The impacts of carbendazim were assessed in experiments conducted at 20°C (experiment 1) and 30°C (experiment 3) using four sublethal concentrations of carbendazim (0.01, 0.02, and 0.04) and controls. An additional experiment (experiment 2) on the next generation (F1) was conducted at 20°C, using the offspring of the second clutches of M. micrura from each of the corresponding treatments of the experiment 1. The increase in temperature from 20 to 30°C significantly reduced always the average lifespan and life expectancy at birth, while raised the rate of population increase, net reproductive rate, and reproductive effort, in controls but not in carbendazim treatments. Higher temperature also increased male/female ratio. The patterns of survivorship curves were weakly affected by carbendazim exposure, but increase in concentration of this fungicide reduced offspring production, reproductive rates, and the rate of population increase, more noticeable at the higher temperature. These detrimental effects were much more striking in the F1 experiment, in which females were unable to produce viable offspring in the two highest carbendazim concentrations, although survival and swimming behavior were not significantly affected. This indicates that sensitivity to the toxicant is greater during egg development and that the fungicide acts as an endocrine disruptor. The presence of carbendazim in the medium resulted in higher male production as compared with controls, indicating also its effect on egg development. We also encountered a few individuals, with abnormal sexual secondary characters (males with reduced antennule length, similar to female antennules) at the highest carbendazim concentration. The role of carbendazim on the demography of cladocerans in natural systems, subject to temperature increase, is discussed taking into account the persistence of this chemical and its elevated impact in the successive generations (through the higher sensitivity of the developing eggs to the chemical at high temperatures). Cladoceran bioassays starting with neonates, which usually utilize offspring as sublethal endpoints should include the first generation to evaluate fecundity responses.     

Unique corneal tomography features of allergic eye disease identified by OCT imaging and artificial intelligence

The purpose of this study was to assess unique corneal tomographic parameters of allergic eye disease (AED) using optical coherence tomography (OCT) and artificial intelligence (AI). A total of 57 eyes diagnosed with AED were included. The curvature and aberrations of the air‐epithelium (A‐E) and epithelium‐Bowman's layer (E‐B) interfaces were calculated. Random forest AI models were built combing this data with the parameters of healthy, forme fruste keratoconus (FFKC) and KC eyes. The AI models were cross‐validated with 3‐fold random sampling. Each model was limited to 10 trees. The AI model incorporating both A‐E and E‐B parameters provided the best classification of AED eyes (area under the curve = 0.958, sensitivity = 80.7%, specificity = 98.5%, precision = 88.2%). Further, the E‐B interface parameters provided the highest information gain in the AI model. A few AED eyes (n = 9) had tomography parameters similar to FFKC and KC eyes and may be at risk of progression to KC.     

Fish-mediated zooplankton community structure in shallow turbid waters: a mesocosm study

Wetlands Ecology and Management - Turbidity influences the success of fish feeding, but little is known about the difference in the effects of turbidity as a result of organic and inorganic matter....