Thrombin is a novel regulator of hexokinase activity in mesangial cells

Thrombin is a novel regulator of hexokinase activity in mesangial cells.BackgroundHexokinase (HK) activity is fundamentally important to cellular glucose uptake and metabolism. Phorbol esters increase both HK activity and glucose utilization in cultured mesangial cells via a protein kinase C (PKC)- and extracellular signal-regulated kinases 1 and 2 (ERK1/2)-dependent mechanism. In adult kidneys, increased HK activity has been reported in both glomerular injury and in diabetes, but the mechanisms responsible for these changes are unknown. Thrombin, a known activator of both PKC and ERK1/2, is increased in the settings of renal injury and diabetes. Thus, thrombin may contribute to the observed changes in HK activity in vivo.MethodsThrombin and thrombin receptor agonists were tested for the ability to increase HK activity and glucose metabolism in murine mesangial (SV40 MES 13) cells. ERK1/2 activation was also evaluated in parallel. Thrombin inhibition (hirudins), PKC depletion, Ser-Thr kinase inhibition (H-7), MEK1/2 inhibition (PD98059), pertussis toxin (PTX), and general inhibitors of transcription or translation were then tested for the ability to attenuate these effects.ResultsThrombin (≥0.01 U/mL) mimicked the effect of phorbol esters, increasing HK activity 50% within 12 to 24 hours (P < 0.05). This effect was inhibited by hirudins, mimicked by thrombin receptor agonists, and accompanied by increased Glc utilization. H-7, PD98059, and general inhibitors of transcription or translation—but not PTX—prevented thrombin-induced HK activity at 24 hours. PKC depletion and PD98059 also blocked the associated phosphorylation and activation of ERK1/2.ConclusionsThrombin increases mesangial cell HK activity via a PTX-insensitive mechanism involving thrombin receptor activation, PKC-dependent activation of ERK1/2, and both ongoing gene transcription and de novo protein synthesis. As such, thrombin is a novel regulator of HK activity in mesangial cells and may play a role in coupling renal injury to metabolism

Contrasting seed biology of two ornamental palms: Pygmy Date Palm (Phoenix roebelenii O’Brien) and Fishtail Palm (Caryota urens L.)

The Arecaceae family includes palm trees of economic importance both as a source of agricultural produce and asornamental components in landscaping projects. Pygmy date palm (Phoenix roebelenii) and solitary fishtail palm (Caryotaurens) are well known landscaping plants today. Both species have their origin in Southeast Asia and, especially C. urens iswidespread in peninsular India and Sri Lanka. They are multipurpose species with a variety of applications and thus veryheavily utilized. Knowledge of palm seed storage biology will improve their conservation prospects. In present studies, freshseed moisture content in P. roebelenii was recorded to be 30% with germinability of 98%. After desiccation to 8% moisturegerminability was reduced to 90% and the seeds survived cryo-exposure. Fresh seeds of C. urens, with initial moisturecontent of 34% and 95% germinability could be desiccated to lowest level of only 29% moisture content, with complete lossof germinability. Fresh as well as desiccated seeds of this species did not survive cryo-exposure. While the seeds of C. urensstored at room temperature lost their germinability by 110 days, seeds of P. roebelenii could germinate even after 9 monthsof storage. P. roebelenii is proven to exhibit orthodox seed storage behaviour while C. urens is found to exhibit recalcitrantseed storage behaviour. Long-term ex situ cryo-conservation in the form of seed gene banks would be suitable for seedpropagated orthodox palm species and a few germplasm centres may be established for recalcitrant Indian palms in suitablebio-geographic regions as a complimentary ex situ conservation

Analysis of natural product regulation of cannabinoid receptors in the treatment of human disease

The organized, tightly regulated signaling relays engaged by the cannabinoid receptors (CBs) and their ligands, G proteins and other effectors, together constitute the endocannabinoid system (ECS). This system governs many biological functions including cell proliferation, regulation of ion transport and neuronal messaging. This review will firstly examine the physiology of the ECS, briefly discussing some anomalies in the relay of the ECS signaling as these are consequently linked to maladies of global concern including neurological disorders, cardiovascular disease and cancer. While endogenous ligands are crucial for dispatching messages through the ECS, there are also commonalities in binding affinities with copious exogenous ligands, both natural and synthetic. Therefore, this review provides a comparative analysis of both types of exogenous ligands with emphasis on natural products given their putative safer efficacy and the role of Δ9-tetrahydrocannabinol (Δ9-THC) in uncovering the ECS. Efficacy is congruent to both types of compounds but noteworthy is the effect of a combination therapy to achieve efficacy without unideal side-effects. An example is Sativex that displayed promise in treating Huntington's disease (HD) in preclinical models allowing for its transition to current clinical investigation. Despite the in vitro and preclinical efficacy of Δ9-THC to treat neurodegenerative ailments, its psychotropic effects limit its clinical applicability to treating feeding disorders. We therefore propose further investigation of other compounds and their combinations such as the triterpene, α,β-amyrin that exhibited greater binding affinity to CB1 than CB2 and was more potent than Δ9-THC and the N-alkylamides that exhibited CB2 selective affinity; the latter can be explored towards peripherally exclusive ECS modulation. The synthetic CB1 antagonist, Rimonabant was pulled from commercial markets for the treatment of diabetes, however its analogue SR144528 maybe an ideal lead molecule towards this end and HU-210 and Org27569 are also promising synthetic small molecules

Els nivells magdalenians de la Cova de les Cendres (Teulada, Moraira) : resultats del sondeig del quadre A-17

Villaverde Bonilla, Valentin - [email protected] Badal Garcia, Ernestina - [email protected]

Electronic Health Services: An Introduction to Theory and Application

Information and communication technologies have made dramatic changes in our lives. Healthcare communities also made use of these technologies. Using computerized medical knowledge, electronic patients’ information and telecommunications a lot of applications are now established throughout the world. These include better ways of information management, remote education, telemedicine and public services. Yet, a lot of people don't know about these technologies and their applications. Understanding the concepts and ideologies behind these terms, knowing how they will be implemented, what is it like to use them and what benefit will be gained, are basic knowledge steps approaching these technologies. Difficulties using these services, especially in developing countries should not be neglected or underestimated

Evaluation of the early impacts of the better cotton initiative on smallholder cotton producers in Kurnool District, India: Baseline report

The Better Cotton Standard System is a holistic approach to sustainable cotton production that covers all three pillars of sustainability: environmental, social and economic. The main study research questions is - To what extent has the process of becoming or being certified under BCI sustainability standards had an impact (positive or negative, expected or unexpected) upon smallholders (farmers and households) in Kurnool district? What are the economic (yield, productivity, incomes, food security) and social (child labour, farm workers, no discrimination in wages for women) impacts? In order to be able to measure and attribute impact, but also to understand what has created impact and identify lessons, the study employs a theory based evaluation approach. The baseline and interim performance monitoring rounds of the research have been completed. The end line research is planned in 2018-19

A Comparison of Two Ovine Lumbar Intervertebral Disc Injury Models for the Evaluation and Development of Novel Regenerative Therapies

© The Author(s) 2018. Study Design: Large animal research. Objective: Lumbar discectomy is the most commonly performed spinal surgical procedure. We investigated 2 large animal models of lumbar discectomy in order to study the regenerative capacity of mesenchymal stem cells following disc injury. Methods: Twelve adult ewes underwent baseline 3-T magnetic resonance imaging (MRI) followed by lumbar intervertebral disc injury by either drill bit (n = 6) or annulotomy and partial nucleotomy (APN) (n = 6). Necropsies were performed 6 months later. Lumbar spines underwent 3-T and 9.4-T MRI prior to histological, morphological and biochemical analysis. Results: Drill bit-injured (DBI) and APN-injured discs demonstrated increased Pfirrmann grades relative to uninjured controls (P <.005), with no difference between the 2 models. Disc height index loss was greater in the APN group compared with the DBI group (P <.005). Gross morphology injury scores were higher in APN than DBI discs (P <.05) and both were higher than controls (P <.005). Proteoglycan was reduced in the discs of both injury models relative to controls (P <.005), but lower in the APN group (P <.05). Total collagen of the APN group disc regions was higher than DBI and control discs (P <.05). Histology revealed more matrix degeneration, vascular infiltration, and granulation in the APN model. Conclusion: Although both models produced disc degeneration, the APN model better replicated the pathobiology of human discs postdiscectomy. We therefore concluded that the APN model was a more appropriate model for the investigation of the regenerative capacity of mesenchymal stem cells administered postdiscectomy