Phenotypic Plasticity and Effects of Selection on Cell Division Symmetry in Escherichia coli

Aging has been demonstrated in unicellular organisms and is presumably due to asymmetric distribution of damaged proteins and other components during cell division. Whether the asymmetry-induced aging is inevitable or an adaptive and adaptable response is debated. Although asymmetric division leads to aging and death of some cells, it increases the effective growth rate of the population as shown by theoretical and empirical studies. Mathematical models predict on the other hand, that if the cells divide symmetrically, cellular aging may be delayed or absent, growth rate will be reduced but growth yield will increase at optimum repair rates. Therefore in nutritionally dilute (oligotrophic) environments, where growth yield may be more critical for survival, symmetric division may get selected. These predictions have not been empirically tested so far. We report here that Escherichia coli grown in oligotrophic environments had greater morphological and functional symmetry in cell division. Both phenotypic plasticity and genetic selection appeared to shape cell division time asymmetry but plasticity was lost on prolonged selection. Lineages selected on high nutrient concentration showed greater frequency of presumably old or dead cells. Further, there was a negative correlation between cell division time asymmetry and growth yield but there was no significant correlation between asymmetry and growth rate. The results suggest that cellular aging driven by asymmetric division may not be hardwired but shows substantial plasticity as well as evolvability in response to the nutritional environment

Invasion of ovarian cancer cells is induced by PITX2-mediated activation of TGF-β and Activin-A

Background:Most ovarian cancers are highly invasive in nature and the high burden of metastatic disease make them a leading cause of mortality among all gynaecological malignancies. The homeodomain transcription factor, PITX2 is associated with cancer in different tissues. Our previous studies demonstrated increased PITX2 expression in human ovarian tumours. Growing evidence linking activation of TGF-β pathway by homeodomain proteins prompted us to look for the possible involvement of this signalling pathway in PITX2-mediated progression of ovarian cancer. Methods: The status of TGF-β signalling in human ovarian tissues was assessed by immunohistochemistry. The expression level of TGFB/INHBA and other invasion-associated genes was measured by quantitative-PCR (Q-PCR) and Western Blot after transfection/treatments with clones/reagents in normal/cancer cells. The physiological effect of PITX2 on invasion/motility was checked by matrigel invasion and wound healing assay. The PITX2- and activin-induced epithelial-mesenchymal transition (EMT) was evaluated by Q-PCR of respective markers and confocal/phase-contrast imaging of cells. Results: Human ovarian tumours showed enhanced TGF-β signalling. Our study uncovers the PITX2-induced expression of TGFB1/2/3 as well as INHBA genes (p < 0.01) followed by SMAD2/3-dependent TGF-β signalling pathway. PITX2-induced TGF-β pathway regulated the expression of invasion-associated genes, SNAI1, CDH1 and MMP9 (p < 0.01) that accounted for enhanced motility/invasion of ovarian cancers. Snail and MMP9 acted as important mediators of PITX2-induced invasiveness of ovarian cancer cells. PITX2 over-expression resulted in loss of epithelial markers (p < 0.01) and gain of mesenchymal markers (p < 0.01) that contributed significantly to ovarian oncogenesis. PITX2-induced INHBA expression (p < 0.01) contributed to EMT in both normal and ovarian cancer cells. Conclusions: Overall, our findings suggest a significant contributory role of PITX2 in promoting invasive behaviour of ovarian cancer cells through up-regulation of TGFB/INHBA. We have also identified the previously unknown involvement of activin-A in promoting EMT. Our work provides novel mechanistic insights into the invasive behavior of ovarian cancer cells. The extension of this study have the potential for therapeutic applications in future

Nutritional considerations during prolonged exposure to a confined, hyperbaric, hyperoxic environment: Recommendations for saturation divers

Saturation diving is an occupation that involves prolonged exposure to a confined, hyperoxic, hyperbaric environment. The unique and extreme environment is thought to result in disruption to physiological and metabolic homeostasis, which may impact human health and performance. Appropriate nutritional intake has the potential to alleviate and/or support many of these physiological and metabolic concerns, whilst enhancing health and performance in saturation divers. Therefore, the purpose of this review is to identify the physiological and practical challenges of saturation diving and consequently provide evidence-based nutritional recommendations for saturation divers to promote health and performance within this challenging environment. Saturation diving has a high-energy demand, with an energy intake of between 44 and 52 kcal/kg body mass per day recommended, dependent on intensity and duration of underwater activity. The macronutrient composition of dietary intake is in accordance with the current Institute of Medicine guidelines at 45-65 % and 20-35 % of total energy intake for carbohydrate and fat intake, respectively. A minimum daily protein intake of 1.3 g/kg body mass is recommended to facilitate body composition maintenance. Macronutrient intake between individuals should, however, be dictated by personal preference to support the attainment of an energy balance. A varied diet high in fruit and vegetables is highly recommended for the provision of sufficient micronutrients to support physiological processes, such as vitamin B12 and folate intake to facilitate red blood cell production. Antioxidants, such as vitamin C and E, are also recommended to reduce oxidised molecules, e.g. free radicals, whilst selenium and zinc intake may be beneficial to reinforce endogenous antioxidant reserves. In addition, tailored hydration and carbohydrate fueling strategies for underwater work are also advised

Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?

Neurodegenerative disorders show an increasing prevalence in a number of highly developed countries. Often, these diseases require life-long treatment mostly with drugs which are costly and mostly accompanied by more or less serious side-effects. Their heterogeneous manifestation, severity and outcome pose the need for individualised treatment options. There is an intensive search for new strategies not only for treating but also for preventing these diseases. Green tea and green tea extracts seem to be such a promising and safe alternative. However, data regarding the beneficial effects and possible underlying mechanism, specifically in clinical trials, are rare and rather controversial or non-conclusive. This review outlines the existing evidence from preclinical studies (cell and tissue cultures and animal models) and clinical trials regarding preventive and therapeutic effects of epigallcatechin-3-gallate in neurodegenerative diseases and considers antioxidative vs. pro-oxidative properties of the tea catechin important for dosage recommendations

Mechanisms and therapeutic applications of electromagnetic therapy in Parkinson's disease

© 2015 Vadalà et al. Electromagnetic therapy is a non-invasive and safe approach for the management of several pathological conditions including neurodegenerative diseases. Parkinson's disease is a neurodegenerative pathology caused by abnormal degeneration of dopaminergic neurons in the ventral tegmental area and substantia nigra pars compacta in the midbrain resulting in damage to the basal ganglia. Electromagnetic therapy has been extensively used in the clinical setting in the form of transcranial magnetic stimulation, repetitive transcranial magnetic stimulation, high-frequency transcranial magnetic stimulation and pulsed electromagnetic field therapy which can also be used in the domestic setting. In this review, we discuss the mechanisms and therapeutic applications of electromagnetic therapy to alleviate motor and non-motor deficits that characterize Parkinson's disease