Waste-to-Energy Decision Support Method for Forward Deployed Forces

Solid waste is generated in mass quantities at forward deployed locations due to their temporary nature. Current handling practices are inefficient and wasteful, and do not reuse the energy inherently available in the waste. This research identifies potential energy, convoy, and casualty reductions that can be realized through the use of waste-to-energy (WTE) at contingency locations. It identifies typical variance expected in the solid waste stream and illustrates decision factors for determining the type of WTE technology that is best suited for a particular situation. A statistical analysis was conducted on the waste streams of five contingency bases to determine energy content of a typical sample at any location for WTE planning purposes. Energy and risk reduction was calculated and a decision tree was developed to allow personnel to choose a technology type that would best suit their waste disposal needs. Results indicate that variability in the waste stream significantly affects results of each analysis and that the typical sample energy content from the entire waste stream is much lower than either of the other waste streams

CEP162 is an axoneme-recognition protein promoting ciliary transition zone assembly at the cilia base

The transition zone (TZ) is a specialized compartment found at the base of cilia, adjacent to the centriole distal end, where axonemal microtubules (MTs) are heavily cross-linked to the surrounding membrane to form a barrier that gates the ciliary compartment. A number of ciliopathy molecules have been found to associate with the TZ, but factors that directly recognize axonemal MTs to specify TZ assembly at the cilia base remain unclear. Here, through quantitative centrosome proteomics, we identified an axoneme-associated protein, CEP162, tethered specifically at centriole distal ends to promote TZ assembly. CEP162 interacts with core TZ components, and mediates their association with MTs. Loss of CEP162 arrests ciliogenesis at the stage of TZ assembly. Abolishing its centriolar tethering, however, allows CEP162 to stay on the growing end of the axoneme, and ectopically assemble TZ components at cilia tips. This generates extra-long cilia with strikingly swollen tips that actively release ciliary contents into the extracellular environment. CEP162 is thus an axoneme-recognition protein “pre-tethered” at centriole distal ends prior to ciliogenesis to promote and restrict TZ formation specifically at the cilia base

Mutant DMPK 3′-UTR transcripts disrupt C2C12 myogenic differentiation by compromising MyoD

Myotonic dystrophy (DM) is caused by two similar noncoding repeat expansion mutations (DM1 and DM2). It is thought that both mutations produce pathogenic RNA molecules that accumulate in nuclear foci. The DM1 mutation is a CTG expansion in the 3′ untranslated region (3′-UTR) of dystrophia myotonica protein kinase (DMPK). In a cell culture model, mutant transcripts containing a (CUG)200 DMPK 3′-UTR disrupt C2C12 myoblast differentiation; a phenotype similar to what is observed in myoblast cultures derived from DM1 patient muscle. Here, we have used our cell culture model to investigate how the mutant 3′-UTR RNA disrupts differentiation. We show that MyoD protein levels are compromised in cells that express mutant DMPK 3′-UTR transcripts. MyoD, a transcription factor required for the differentiation of myoblasts during muscle regeneration, activates differentiation-specific genes by binding E-boxes. MyoD levels are significantly reduced in myoblasts expressing the mutant 3′-UTR RNA within the first 6 h under differentiation conditions. This reduction correlates with blunted E-box–mediated gene expression at time points that are critical for initiating differentiation. Importantly, restoring MyoD levels rescues the differentiation defect. We conclude that mutant DMPK 3′-UTR transcripts disrupt myoblast differentiation by reducing MyoD levels below a threshold required to activate the differentiation program

NPHP4 Variants Are Associated With Pleiotropic Heart Malformations

Rationale: Congenital heart malformations are a major cause of morbidity and mortality, especially in young children. Failure to establish normal left-right (L-R) asymmetry often results in cardiovascular malformations and other laterality defects of visceral organs. Objective: To identify genetic mutations causing cardiac laterality defects. Methods and Results: We performed a genome-wide linkage analysis in patients with cardiac laterality defects from a consanguineous family. The patients had combinations of defects that included dextrocardia, transposition of great arteries, double-outlet right ventricle, atrioventricular septal defects, and caval vein abnormalities. Sequencing of positional candidate genes identified mutations in NPHP4. We performed mutation analysis of NPHP4 in 146 unrelated patients with similar cardiac laterality defects. Forty-one percent of these patients also had laterality defects of the abdominal organs. We identified 8 additional missense variants that were absent or very rare in control subjects. To study the role of nphp4 in establishing L-R asymmetry, we used antisense morpholinos to knockdown nphp4 expression in zebrafish. Depletion of nphp4 disrupted L-R patterning as well as cardiac and gut laterality. Cardiac laterality defects were partially rescued by human NPHP4 mRNA, whereas mutant NPHP4 containing genetic variants found in patients failed to rescue. We show that nphp4 is involved in the formation of motile cilia in Kupffer's vesicle, which generate asymmetrical fluid flow necessary for normal L-R asymmetry. Conclusions: NPHP4 mutations are associated with cardiac laterality defects and heterotaxy. In zebrafish, nphp4 is essential for the development and function of Kupffer's vesicle cilia and is required for global L-R patterning

Prostaglandin signalling regulates ciliogenesis by modulating intraflagellar transport

Cilia are microtubule-based organelles that mediate signal transduction in a variety of tissues. Despite their importance, the signalling cascades that regulate cilium formation remain incompletely understood. Here we report that prostaglandin signalling affects ciliogenesis by regulating anterograde intraflagellar transport (IFT). Zebrafish leakytail (lkt) mutants show ciliogenesis defects, and the lkt locus encodes an ATP-binding cassette transporter (ABCC4). We show that Lkt/ABCC4 localizes to the cell membrane and exports prostaglandin E2 (PGE2), a function that is abrogated by the Lkt/ABCC4T804M mutant. PGE2 synthesis enzyme cyclooxygenase-1 and its receptor, EP4, which localizes to the cilium and activates the cyclic-AMP-mediated signalling cascade, are required for cilium formation and elongation. Importantly, PGE2 signalling increases anterograde but not retrograde velocity of IFT and promotes ciliogenesis in mammalian cells. These findings lead us to propose that Lkt/ABCC4-mediated PGE2 signalling acts through a ciliary G-protein-coupled receptor, EP4, to upregulate cAMP synthesis and increase anterograde IFT, thereby promoting ciliogenesis

Adhesive/Repulsive Codes in Vertebrate Forebrain Morphogenesis.

The last fifteen years have seen the identification of some of the mechanisms involved in anterior neural plate specification, patterning, and morphogenesis, which constitute the first stages in the formation of the forebrain. These studies have provided us with a glimpse into the molecular mechanisms that drive the development of an embryonic structure, and have resulted in the realization that cell segregation in the anterior neural plate is essential for the accurate progression of forebrain morphogenesis. This review summarizes the latest advances in our understanding of mechanisms of cell segregation during forebrain development, with and emphasis on the impact of this process on the morphogenesis of one of the anterior neural plate derivatives, the eyes