Heritable germline epimutation of MSH2 in a family with hereditary nonpolyposis colorectal cancer

Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.     

Systemic Development of Leadership: Action Research in an Indian Manufacturing Organization

This insider action research study differentiates between developing leaders and leadership, evolves a systemic leadership model, and intervenes on the human, social and processes dimensions for developing leadership. This is a real-time study and responds to the organizational reality of fast pace of change and its systemic nature. Consequently, the research too is fast to guide actions and influence positive changes in the organization. As the action research addresses a systemic reality, research and contributions are in multiple aspects, with new techniques having huge implications for theory building as well as improving practice. The study provides a structural solution to perceived lack of commitment in senior colleagues—a syndrome I acronym as HILE (High Intentions and Lukewarm Execution)–by re-designing organizational processes and making time available for its effective utilization in developing leadership. A new technique of triggering major changes in organizations termed “concept sublimation” distils concept from the statements of major stakeholder and sublimates it from lower to higher unit of analysis and to higher levels of positivity. Statistical simplification of a competency framework by applying concepts from Euclidian geometry and making it effective is yet a unique contribution of this action research study. The study adapts the competing values framework in developing a method of assessing cultural congruence of a candidate with the culture of the organization. The uniqueness of the study lies in bridging the gap in the literature by actually and systemically developing leadership in an organization and providing pragmatic insights on developing leadership while also creating knowledge for theory building.     

<Emphasis Type="Italic">Dictyostelium</Emphasis> dynamin B modulates cytoskeletal structures and membranous organelles

Dictyostelium discoideum cells produce five dynamin family proteins. Here, we show that dynamin B is the only member of this group of proteins that is initially produced as a preprotein and requires processing by mitochondrial proteases for formation of the mature protein. Our results show that dynamin B-depletion affects many aspects of cell motility, cell-cell and cell-surface adhesion, resistance to osmotic shock, and fatty acid metabolism. The mature form of dynamin B mediates a wide range and unique combination of functions. Dynamin B affects events at the plasma membrane, peroxisomes, the contractile vacuole system, components of the actin-based cytoskeleton, and cell adhesion sites. The modulating effect of dynamin B on the activity of the contractile vacuole system is unique for the Dictyostelium system. Other functions displayed by dynamin B are commonly associated with either classical dynamins or dynamin-related proteins.     

Energy-efficient spectrum-aware clustering for cognitive radio sensor networks

As a smart combination of cognitive radio networks and wireless sensor networks, recently introduced cognitive radio sensor network (CRSN) poses new challenges to the design of topology maintenance techniques for dynamic primary-user activities. This paper aims to provide a solution to the energy-efficient spectrum-aware CRSN clustering problem. Specifically, we design the clustered structure, establish a network-wide energy consumption model and determine the optimal number of clusters. We then employ the ideas from constrained clustering and propose both a centralized spectrum-aware clustering algorithm and a distributed spectrum-aware clustering (DSAC) protocol. Through extensive simulations, we demonstrate that DSAC can effectively form clusters under a dynamic spectrum-aware constraint. Moreover, DSAC exhibits preferable scalability and stability with its low complexity and quick convergence under dynamic spectrum variation.     

RGS2 regulates signal transduction in olfactory neurons by attenuating activation of adenylyl cyclase III

The heterotrimeric G-protein Gs couples cell-surface receptors to the activation of adenylyl cyclases and cyclic AMP production (reviewed in refs 1, 2). RGS proteins, which act as GTPase-activating proteins (GAPs) for the G-protein alpha-subunits alpha(i) and alpha(q), lack such activity for alpha(s) (refs 3-6). But several RGS proteins inhibit cAMP production by Gs-linked receptors. Here we report that RGS2 reduces cAMP production by odorant-stimulated olfactory epithelium membranes, in which the alpha(s) family member alpha(olf) links odorant receptors to adenylyl cyclase activation. Unexpectedly, RGS2 reduces odorant-elicited cAMP production, not by acting on alpha(olf) but by inhibiting the activity of adenylyl cyclase type III, the predominant adenylyl cyclase isoform in olfactory neurons. Furthermore, whole-cell voltage clamp recordings of odorant-stimulated olfactory neurons indicate that endogenous RGS2 negatively regulates odorant-evoked intracellular signalling. These results reveal a mechanism for controlling the activities of adenylyl cyclases, which probably contributes to the ability of olfactory neurons to discriminate odours.     

SEPRAN:A Versatile Finite-Element Package for a Wide Variety of Problems in Geosciences

Numerical modelling of geological processes, such as mantle convection, flow in porous media, and geothermal heat transfer, has become quite common with the increase in computing and the availability o...