Protein Phosphatase 2A Mediates Dormancy of Glioblastoma Multiforme-Derived Tumor Stem-Like Cells during Hypoxia

The hypoxic microenvironment of glioblastoma multiforme (GBM) is thought to increase resistance to cancer therapies. Recent evidence suggests that hypoxia induces protein phosphatase 2A (PP2A), a regulator of cell cycle and cell death. The effects of PP2A on GBM tumor cell proliferation and survival during hypoxic conditions have not been studied.Expression of PP2A subunits and HIF-α proteins was measured in 65 high-grade astrocytoma and 18 non-neoplastic surgical brain specimens by western blotting. PP2A activity was measured by an immunoprecipitation assay. For in vitro experiments, GBM-derived tumor stem cell-like cells (TSCs) were exposed to severe hypoxia produced by either CoCl₂ or 1% O₂. PP2A activity was inhibited either by okadaic acid or by shRNA depletion of the PP2A C subunit. Effects of PP2A activity on cell cycle progression and cell survival during hypoxic conditions were assessed using flow cytometry.In our patient cohort, PP2A activity was positively correlated with HIF-1∝ protein expression (P = 0.002). Patients with PP2A activity levels above 160 pMP had significantly worse survival compared to patients with levels below this threshold (P = 0.002). PP2A activity was an independent predictor of survival on multivariable analysis (P = 0.009). In our in vitro experiments, we confirmed that severe hypoxia induces PP2A activity in TSCs 6 hours after onset of exposure. PP2A activity mediated G1/S phase growth inhibition and reduced cellular ATP consumption in hypoxic TSCs. Conversely, inhibition of PP2A activity led to increased cell proliferation, exhaustion of intracellular ATP, and accelerated P53-independent cell death of hypoxic TSCs.Our results suggest that PP2A activity predicts poor survival in GBM. PP2A appears to reduce the metabolic demand of hypoxic TSCs and enhances tumor cell survival. Modulation of PP2A may be a potential target for cancer therapy

Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number

Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

A Hybrid Communication Protocol For Cellular Architecture Using Energy-Efficient AODV

Abstract- Cellular mobile communication nowadays is one of the fastest growing means of communication. With the load on the channel between base stations and mobile hosts increasing, there is an increasing demand on the communication means to be energy efficient. Some of the algorithms like AODV have already come up in the mobile adhoc networks to counter the problems of excessive energy consumption. In this paper we have proposed a new energy efficient routing scheme for communication in cellular networks that uses the idea of AODV and the existing communication scheme used in cellular networks. The proposed work also offers efficient handling of packet loss during handoff

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Not AvailableIn an ongoing field experiment, organic and conventional farming (control) were compared for onion bulb yield, biochemical quality, soil organic carbon (SOC), and microbial activity after the sixth cropping cycle. The treatments used for organic production were farmyard manure (FYM, 20,000 kg ha−1), poultry manure (PM, 10,000 kg ha−1), vermicompost (VC, 10,000 kg ha−1), neem cake (NC, 5000 kg ha−1), and a combination of FYM (5000 kg ha−1), PM (2500 kg ha−1), VC (2500 kg ha−1), and NC (1250 kg ha−1); all treatments were compared with the control. Organic treatments produced 24.6–43.6% lower yield consistently for 6 years than the control treatment. No significant difference was observed between PM, FYM, and VC treatments for the bulb yield. Bulb analysis during the sixth year indicated that plants that received FYM, PM, or VC had higher levels of total phenol, total flavonoid, ascorbic acid, and quercetin-3-glucoside than the control plants. All the five organically treated sets had significantly higher values of SOC, microbial population, fungal-to-bacterial ratio, and dehydrogenase activity than the control and the initial values in each treated set. The results indicate that FYM, PM, or VC application enhances biochemical quality and organic farming is more sustainable than conventional farming.Not Availabl

Not Available

Not AvailableIn an ongoing field experiment, organic and conventional farming (control) were compared for onion bulb yield, biochemical quality, soil organic carbon (SOC), and microbial activity after the sixth cropping cycle. The treatments used for organic production were farmyard manure (FYM, 20,000 kg ha−1), poultry manure (PM, 10,000 kg ha−1), vermicompost (VC, 10,000 kg ha−1), neem cake (NC, 5000 kg ha−1), and a combination of FYM (5000 kg ha−1), PM (2500 kg ha−1), VC (2500 kg ha−1), and NC (1250 kg ha−1); all treatments were compared with the control. Organic treatments produced 24.6–43.6% lower yield consistently for 6 years than the control treatment. No significant difference was observed between PM, FYM, and VC treatments for the bulb yield. Bulb analysis during the sixth year indicated that plants that received FYM, PM, or VC had higher levels of total phenol, total flavonoid, ascorbic acid, and quercetin-3-glucoside than the control plants. All the five organically treated sets had significantly higher values of SOC, microbial population, fungal-to-bacterial ratio, and dehydrogenase activity than the control and the initial values in each treated set. The results indicate that FYM, PM, or VC application enhances biochemical quality and organic farming is more sustainable than conventional farming.Not Availabl

Novel single‐operator through‐the‐scope traction device for endoscopic submucosal dissection: Outcomes of a multicenter randomized pilot ex‐vivo study in trainees with limited endoscopic submucosal dissection experience (with video)

ObjectivesEndoscopic submucosal dissection is a technically demanding procedure. The pilot study aimed to prospectively evaluate the efficacy and safety of a novel single-operator through-the-scope dynamic traction device among trainees with limited endoscopic submucosal dissection (ESD) experience.MethodsRandomized, controlled, pilot study comparing traction-assisted ESD (T-ESD) versus conventional ESD (C-ESD) in an ex-vivo porcine stomach model. Trainees were randomized to group 1 (T-ESD followed by C-ESD) and group 2 (C-ESD followed by T-ESD). Lesions were created on the gravity-dependent area of the stomachs. The primary outcome was submucosal dissection speed. Secondary outcomes included differences in en-bloc resection, adverse events, and workload, assessed by the National Aeronautical and Space Administration Task Load Index (NASA-TLX).ResultsFive trainees performed two T-ESD and two C-ESD each, for a total of 20 procedures. Submucosal dissection speed was significantly faster in the T-ESD group compared to the C-ESD group (43.32 ± 22.61 vs. 24.19 ± 15.86 mm2/min; p = 0.042). En-bloc resection was achieved in 60% with T-ESD and 70% with C-ESD (p = 1.00). The muscle injury rate was higher in the C-ESD group (50% vs. 10%; p = 0.21) with 1 perforation reported with C-ESD and none with T-ESD. NASA-TLX physical demand was lower with T-ESD compared to C-ESD (4.5 ± 2.17 vs. 6.9 ± 2.50; p = 0.03).ConclusionT-ESD resulted in faster submucosal dissection and less physical demand when compared to C-ESD, as performed by trainees in an ex-vivo gravity-dependent model. Future studies are needed to assess its role in human ESD cases

Comparison of organic and conventional farming for onion yield, biochemical quality, soil organic carbon, and microbial population

<p>In an ongoing field experiment, organic and conventional farming (control) were compared for onion bulb yield, biochemical quality, soil organic carbon (SOC), and microbial activity after the sixth cropping cycle. The treatments used for organic production were farmyard manure (FYM, 20,000 kg ha⁻¹), poultry manure (PM, 10,000 kg ha⁻¹), vermicompost (VC, 10,000 kg ha⁻¹), neem cake (NC, 5000 kg ha⁻¹), and a combination of FYM (5000 kg ha⁻¹), PM (2500 kg ha⁻¹), VC (2500 kg ha⁻¹), and NC (1250 kg ha⁻¹); all treatments were compared with the control. Organic treatments produced 24.6–43.6% lower yield consistently for 6 years than the control treatment. No significant difference was observed between PM, FYM, and VC treatments for the bulb yield. Bulb analysis during the sixth year indicated that plants that received FYM, PM, or VC had higher levels of total phenol, total flavonoid, ascorbic acid, and quercetin-3-glucoside than the control plants. All the five organically treated sets had significantly higher values of SOC, microbial population, fungal-to-bacterial ratio, and dehydrogenase activity than the control and the initial values in each treated set. The results indicate that FYM, PM, or VC application enhances biochemical quality and organic farming is more sustainable than conventional farming.</p