Immune effects of mesenchymal stem cells: implications for Charcot-Marie-Tooth disease

Mesenchymal stem cell (MSC) therapy is the most clinically advanced form of cell therapy, second to hematopoietic stem cell transplants. To date, MSC have been used for immune modulation in conditions such as Graft Versus Host Disease (GVHD) and Crohn's Disease, for which Phase III clinical trials are currently in progress. Here, we review the immunological properties of MSC and make a case for their use in treatment of Charcot-Marie-Tooth disease type 1 (CMT1), a group of inherited peripheral neuropathies. CMT1 is characterized by demyelination and aberrant immune activation making this condition an ideal target for exploration of MSC therapy, given the ability of these cells to promote sheath regeneration as well as suppress inflammation. Studies supporting this hypothesis will be presented and placed into the context of other cell-based approaches that are theoretically feasible. Given that MSCs selectively home to areas of inflammation, as well as exert effects in an allogeneic manner, the possibility of an "off the shelf" therapy for CMT1 will be discussed.     

Regarding paper: "robustness of shrunken predictors in stratified population"

Article http://dx.doi.org/10.1002/bimj.4710360113 Authors reply http://dx.doi.org/10.1002/bimj.200810432     

Alterations in the hepatic enzymes following experimental lead poisoning

An investigation on the influence of lead toxicity on some of the hepatic enzymes was studied in rats both after a shorter interval of 15 d and after longer intervals of 60 and 90 d. Three different doses of lead as 5, 10, and 50 mg/kg body wt were administered orally on every alternate day. Whereas significant inhibition of succinic dehydrogenase was seen following lead poisoning, the activity acid and alkaline phosphatase increased with lead intoxication. The histoarchitecture of the liver was grossly intact. Liver accumulated less lead compared to kidney at 60 and 90 d.     

Control of flowering in rice through synthetic microProteins

Photoperiod‐dependent flowering in rice is regulated by HEADING DATE 1 (Hd1), which acts as both an activator and repressor of flowering in a daylength‐dependent manner. To investigate the use of microProteins as a tool to modify rice sensitivity to the photoperiod, we designed a synthetic Hd1 microProtein (Hd1miP) capable of interacting with Hd1 protein, and overexpressed it in rice. Transgenic OX‐Hd1miP plants flowered significantly earlier than wild type plants when grown in non‐inductive long day conditions. Our results show the potential of microProteins to serve as powerful tools for modulating crop traits and unraveling protein function.     

Diversity,regeneration, and anthropogenic disturbance in major Indian Central Himalayan forest types: implications for conservation

Biodiversity and Conservation - Understanding community structure together with regeneration and disturbance provides a holistic purview of forest health and the necessary management implications...     

Diverse water quality responses to extreme climate events: an introduction

We synthesize and summarize main findings from a special issue examining the origins, evolution, and resilience of diverse water quality responses to extreme climate events resulting from a Chapman Conference of the American Geophysical Union (AGU). Origins refer to sequences of interactive disturbances and antecedent conditions that influence diversification of water quality responses to extreme events. Evolution refers to the amplification, intensification, and persistence of water quality signals across space and time in watersheds. Resilience refers to strategies for managing and minimizing extreme water quality impacts and ecosystem recovery. The contributions of this special issue, taken together, highlight the following: (1) there is diversification in the origins of water quality responses to extreme climate events based on the intensity, duration, and magnitude of the event mediated by previous historical conditions; (2) interactions between climate variability and watershed disturbances (e.g., channelization of river networks, land use change, and deforestation) amplify water quality ‘pulses,’ which can manifest as large changes in chemical concentrations and fluxes over relatively short time periods. In the context of the evolution of water quality responses, results highlight: (3) there are high intensity and long-term climate events, which can generate unique sequences in water quality, which have differential impacts on persistence of water quality problems and ecosystem recovery rates; and (4) ‘chemical cocktails’ or novel mixtures of elements and compounds are transported and transformed during extreme climate events. The main findings regarding resilience to extreme climate events are that: (5) river restoration strategies for reducing pollution from extreme events can be improved by preserving and restoring floodplains, wetlands, and oxbow ponds, which enhance hydrologic and biogeochemical retention, and lengthen the distribution of hydrologic residence times; and (6) the biogeochemical capacity for stream and river ecosystems to retain and transform pollution from landscapes can become “saturated” during floods unless watershed pollution sources are reduced. Finally, the unpredictable occurrence of extreme climate events argues for wider deployment of high-frequency, in situ sensors for monitoring, managing, and modeling diverse water quality responses. These sensors can be used to develop robust proxies for chemical cocktails, detect water quality violations following extreme climate events, and effectively trace the trajectory of water quality recovery in response to managing ecosystem resilience.     

Gene Specific Impedimetric Bacterial DNA Sensor for Rheumatic Heart Disease

An impedimetric mga gene specific DNA sensor was developed by immobilization of single stranded DNA probe onto the screen printed modified gold-dendrimer nanohybrid composite electrode for early and rapid detection of S. pyogenes in human throat swab samples causing rheumatic heart disease. Electrochemical impedance response was measured after hybridization with bacterial single stranded genomic DNA (ssG-DNA) with probe. The sensor was found highly specific to S. pyogenes and can detect as low as 0.01 ng ssDNA in 6 µL sample only in 30 min. The nanohybrid sensor was also tested with non-specific pathogens and characterized by FTIR. An early detection of the pathogen S. pyogenes in human can save damage of mitral and aortic heart valves (rheumatic heart disease) by proper medical care.     

Autophagy delays apoptosis in renal tubular epithelial cells in cisplatin cytotoxicity

One of the major side effects of cisplatin chemotherapy is toxic acute kidney injury due to preferential accumulation of cisplatin in renal proximal tubule epithelial cells and the subsequent injury to these cells. Apoptosis is known as a major mechanism of cisplatin-induced cell death in renal tubular cells. We have also recently demonstrated that autophagy induction is an immediate response of renal tubular epithelial cell exposure to cisplatin. Inhibition of cisplatin-induced autophagy blocks the formation of autophagosomes and enhances cisplatin-induced caspase-3, -6, and -7 activation, nuclear fragmentation and apoptosis. The switch from autophagy to apoptosis by autophagic inhibitors suggests that autophagy induction was responsible for a pre-apoptotic lag phase observed on exposure of renal tubular cells to cisplatin. Our studies provide evidence that autophagy induction in response to cisplatin mounts an adaptive response that suppresses and delays apoptosis. The beneficial effect of autophagy has a potential clinical significance in minimizing or preventing cisplatin nephrotoxicity.     

Discovery of conformationally rigid 3-azabicyclo[3.1.0]hexane-derived dipeptidyl peptidase-IV inhibitors

The induction of conformationally restricted N-(aryl or heteroaryl)-3-azabicyclo[3.1.0]hexane derivatives at P₂ region of compounds of 2-cyanopyrrolidine class was explored to develop novel DPP-IV inhibitors. The synthesis, structure–activity relationship, and selectivity against related proteases are delineated.