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Background: The nucleolus is the site of rRNA synthesis and processing in eukaryotic cells, but its composition remains poorly understood. Results: We have identified a novel nucleolar RNA-associated protein (Nrap) which is highly conserved from yeast (Saccharomyces cerevisiae) to human, with homologues in mouse, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, Schizosaccharomyces pombe, and other species. In the mouse, we have found that Nrap is ubiquitously expressed and is specifically localized in the nucleolus. We have also identified splice variants in human and mouse, and defined the intron-exon structure of the human Nrap gene. Nrap is inherited into daughter nuclei by associating with the condensed chromosomes during mitosis. RNase treatment of permeabilized cells indicated that the nucleolar localization of Nrap is RNA dependent. The effects of actinomycin D, cycloheximide and 5,6-dichloro-beta-D-ribofuranosylbenzimidazole on Nrap expression and distribution in cultured cells suggest that Nrap is associated with the pre-rRNA transcript. Conclusions: Nrap is a large nucleolar protein (of more than 1000 amino acids), and is a new class of protein with new structural and functional motifs. Nrap appears to be associated with ribosome biogenesis by interacting with pre-rRNA primary transcript.

Several studies have estimated the burden of coronary heart disease (CHD) mortality from ambient PM2.5 exposure, however the burden attributable to near roadway air pollution (NRAP) has not been in...

The primary objective of the National Risk Assessment Partnership (NRAP) program is to develop a defensible, generalized, and science-based methodology and platform for quantifying risk profiles at CO2 injection and storage sites. The methodology must incorporate and define the scientific basis for assessing residual risks associated with long-term stewardship and help guide site operational decision-making and risk management. Development of an integrated and risk-based protocol will help minimize uncertainty in the predicted long-term behavior of the CO2 storage site and thereby increase confidence in storage integrity. The risk profile concept has proven useful in conveying the qualitative evolution of risks for CO2 injection and storage site. However, qualitative risk profiles are not sufficient for specifying long-term liability for CO2 storage sites. Because there has been no science-based defensible and robust methodology developed for quantification of risk profiles for CO2 injection and storage, NRAP has been focused on developing a science-based methodology for quantifying risk profiles for various risk proxies.

Background Previous studies have reported adverse effects of either regional or near-roadway air pollution (NRAP) on lung function. However, there has been little study of the joint effects of these exposures. Objectives To assess the joint effects of NRAP and regional pollutants on childhood lung function in the Children9s Health Study. Methods Lung function was measured on 1811 children from eight Southern Californian communities. NRAP exposure was assessed based on (1) residential distance to the nearest freeway or major road and (2) estimated near-roadway contributions to residential nitrogen dioxide (NO 2 ), nitric oxide (NO) and total nitrogen oxides (NO x ). Exposure to regional ozone (O 3 ), NO 2 , particulate matter with aerodynamic diameter 10 ) and 2.5 µm (PM 2.5 ) was measured continuously at community monitors. Results An increase in near-roadway NO x of 17.9 ppb (2 SD) was associated with deficits of 1.6% in forced vital capacity (FVC) (p=0.005) and 1.1% in forced expiratory volume in 1 s (FEV 1 ) (p=0.048). Effects were observed in all communities and were similar for NO 2 and NO. Residential proximity to a freeway was associated with a reduction in FVC. Lung function deficits of 2–3% were associated with regional PM 10 and PM 2.5 (FVC and FEV 1 ) and with O 3 (FEV 1 ), but not NO 2 across the range of exposure between communities. Associations with regional pollution and NRAP were independent in models adjusted for each. The effects of NRAP were not modified by regional pollutant concentrations. Conclusions The results indicate that NRAP and regional air pollution have independent adverse effects on childhood lung function.

The purpose of this study was to develop methodologies for establishing baseline datasets and statistical protocols for determining statistically significant changes between background concentrations and predicted concentrations that would be used to represent a contamination plume in the Gen II models being developed by NRAP’s Groundwater Protection team. The initial effort examined selected portions of two aquifer systems; the urban shallow-unconfined aquifer system of the Edwards-Trinity Aquifer System (being used to develop the ROM for carbon-rock aquifers, and the a portion of the High Plains Aquifer (an unconsolidated and semi-consolidated sand and gravel aquifer, being used to development the ROM for sandstone aquifers). Threshold values were determined for Cd, Pb, As, pH, and TDS that could be used to identify contamination due to predicted impacts from carbon sequestration storage reservoirs, based on recommendations found in the EPA’s ''Unified Guidance for Statistical Analysis of Groundwater Monitoring Data at RCRA Facilities'' (US Environmental Protection Agency 2009). Results from this effort can be used to inform a ''no change'' scenario with respect to groundwater impacts, rather than the use of an MCL that could be significantly higher than existing concentrations in the aquifer.

This white paper accompanies a demonstration model that implements methods for the risk-informed design of monitoring, verification and accounting (RI-MVA) systems in geologic carbon sequestration projects. The intent is that this model will ultimately be integrated with, or interfaced with, the National Risk Assessment Partnership (NRAP) integrated assessment model (IAM). The RI-MVA methods described here apply optimization techniques in the analytical environment of NRAP risk profiles to allow systematic identification and comparison of the risk and cost attributes of MVA design options.

Synaptic scaffolding molecule (S-SCAM) has six PDZ domains through which it interacts with N-methyl- d -aspartate receptors and neuroligin at synaptic junctions. We isolated here a novel S-SCAM-binding protein. This protein has one PDZ, one Ras association, one Ras GDP/GTP exchange protein (Ras GEP) domain, and one C-terminal consensus motif for binding to PDZ domains. We named it nRap GEP (neural Rap GEP). nRap GEP moreover has an incomplete cyclic AMP (cAMP)-binding (CAB) domain. The domain organization of nRap GEP is similar to that of Epac/cAMP–guanine nucleotide exchange factor (GEF) I, except that Epac/cAMP–GEFI has complete CAB and Ras GEP domains but lacks the other two domains and the C-terminal motif. nRap GEP showed GEP activity for Rap1 but did not bind cAMP. nRap GEP was specifically expressed in rat brain. Immunohistochemical analysis revealed that nRap GEP and S-SCAM were localized at synaptic areas of the cerebellum. These results suggest that nRap GEP is a novel neural Rap1-specific GEP which is associated with S-SCAM.

N-RAP is a nebulin-related actin-binding protein found at the myotendon junction in skeletal muscle and at the intercalated disks in cardiac muscle. We mapped the NRAP gene to mouse chromosome 19 using interspecific crosses and to human chromosome 10 using radiation hybrid panels. Comparative analysis of the mouse and human genomes indicates that the NRAP gene is located in regions of conserved synteny between the two species.

The National Risk Assessment Partnership (NRAP) is a US-Department of Energy (US-DOE) effort focused on developing a science-based methodology for quantifying risk profiles at geologic CO 2 sequestration sites. Risk profiles are calculated using an integrated assessment modelling (IAM) approach which treats a geologic CO 2 storage site as a system and uses a system modelling approach to predict time-dependent behaviour of the storage site. We have developed first generation risk profiles associated with a few key potential impacts due to CO 2 leakage from a sequestration reservoir, including change in groundwater quality in a shallow aquifer and return of CO 2 to the atmosphere.

Myofibrillar myopathies (MFMs) are genetically heterogeneous dystrophies characterized by the disintegration of Z-disks and myofibrils and are associated with mutations in genes encoding Z-disk or Z-disk-related proteins. The c.626 C > T (p.P209L) mutation in the BAG3 gene has been described as causative of a subtype of MFM. We report a sporadic case of a 26-year-old Italian woman, affected by MFM with axonal neuropathy, cardiomyopathy, rigid spine, who carries the c.626 C > T mutation in the BAG3 gene. The patient and her non-consanguineous healthy parents and brother were studied with whole exome sequencing (WES) to further investigate the genetic basis of this complex phenotype. In the patient, we found that the BAG3 mutation is associated with variants in the NRAP and FHL1 genes that encode muscle-specific, LIM domain containing proteins. Quantitative real time PCR, immunohistochemistry and Western blot analysis of the patient’s muscular biopsy showed the absence of NRAP expression and FHL1 accumulation in aggregates in the affected skeletal muscle tissue. Molecular dynamic analysis of the mutated FHL1 domain showed a modification in its surface charge, which could affect its capability to bind its target proteins. To our knowledge this is the first study reporting, in a BAG3 MFM, the simultaneous presence of genetic variants in the BAG3 and FHL1 genes (previously described as independently associated with MFMs) and linking the NRAP gene to MFM for the first time.