Identification of novel components of Trypanosoma brucei editosomes

The editosome is a multiprotein complex that catalyzes the insertion and deletion of uridylates that occurs during RNA editing in trypanosomatids. We report the identification of nine novel editosome proteins in Trypanosoma brucei. They were identified by mass spectrometric analysis of functional editosomes that were purified by serial ion exchange/gel permeation chromatography, immunoaffinity chromatography specific to the TbMP63 editosome protein, or tandem affinity purification based on a tagged RNA editing ligase. The newly identified proteins have ribonuclease and/or RNA binding motifs suggesting nuclease function for at least some of these. Five of the proteins are interrelated, as are two others, and one is related to four previously identified editosome proteins. The implications of these findings are discussed

Craters Hosting Radar-Bright Deposits in Mercury's North Polar Region: Areas of Persistent Shadow Determined from MESSENGER Images

Radar-bright features near Mercury's poles were discovered in Earth-based radar images and proposed to be water ice present in permanently shadowed areas. Images from MESSENGER's one-year primary orbital mission provide the first nearly complete view of Mercury’s north polar region, as well as multiple images of the surface under a range of illumination conditions. We find that radar-bright features near Mercury's north pole are associated with locations persistently shadowed in MESSENGER images. Within 10 degrees of the pole, almost all craters larger than 10 km in diameter host radar-bright deposits. There are several craters located near Mercury's north pole with sufficiently large diameters to enable long-lived water ice to be thermally stable at the surface within regions of permanent shadow. Craters located farther south also host radar-bright deposits and show a preference for cold-pole longitudes; thermal models suggest that a thin insulating layer is required to cover these deposits if the radar-bright material consists predominantly of longlived water ice. Many small (less than 10 km diameter) and low-latitude (extending southward to 66 degrees N) craters host radar-bright material, and water ice may not be thermally stable in these craters for ~1 Gy, even beneath an insulating layer. The correlation of radar-bright features with persistently shadowed areas is consistent with the deposits being composed of water ice, and future thermal modeling of small and low-latitude craters has the potential to further constrain the nature, source, and timing of emplacement of the radar-bright material

Comparison of Areas in Shadow from Imaging and Altimetry in the North Polar Region of Mercury and Implications for Polar Ice Deposits

Earth-based radar observations and results from the MESSENGER mission have provided strong evidence that permanently shadowed regions near Mercury's poles host deposits of water ice. MESSENGER's complete orbital image and topographic datasets enable Mercury's surface to be observed and modeled under an extensive range of illumination conditions. The shadowed regions of Mercury's north polar region from 65 deg N to 90 deg N were mapped by analyzing Mercury Dual Imaging System (MDIS) images and by modeling illumination with Mercury Laser Altimeter (MLA) topographic data. The two independent methods produced strong agreement in identifying shadowed areas. All large radar-bright deposits, those hosted within impact craters greater than or equal to 6 km in diameter, collocate with regions of shadow identified by both methods. However, only approximately 46% of the persistently shadowed areas determined from images and approximately 43% of the permanently shadowed areas derived from altimetry host radar-bright materials. Some sizable regions of shadow that do not host radar-bright deposits experience thermal conditions similar to those that do. The shadowed craters that lack radar-bright materials show a relation with longitude that is not related to the thermal environment, suggesting that the Earth-based radar observations of these locations may have been limited by viewing geometry, but it is also possible that water ice in these locations is insulated by anomalously thick lag deposits or that these shadowed regions do not host water ice

Refining genomewide association for growth and fat deposition traits in an F₂ pig population

The identification of genomic regions that affect additive genetic variation and contain genes involved in controlling growth and fat deposition has enormous impact in the farm animal industry (e.g., carcass merit and meat quality). Therefore, a genomewide association study was implemented in an F₂ pig population using a 60,000 SNP marker panel for traits related to growth and fat deposition. Estimated genomic EBV were linearly transformed to calculate SNP effects and to identify genomic positions possibly associated with the genetic variability of each trait. Genomic segments were then defined considering the markers included in a region 1 Mb up- and downstream from the SNP with the smallest -value and a false discovery rate < 0.05 for each trait. The significance for each 2-Mb segment was tested using the Bonferroni correction. Significant SNP were detected on SSC2, SSC3, SSC5, and SSC6, but 2-Mb segment significant effects were observed on SSC3 for weight at birth (wt_birth) and on SSC6 for 10th-rib backfat and last-rib backfat measured by ultrasound at different ages. Furthermore, a 6-Mb segment on SSC6 was also considered because the 2-Mb segments for 10 different fat deposition traits were overlapped. Although the segment effects for each trait remain significant, the proportion of additive variance explained by this larger segment was slightly smaller in some traits. In general, the results confirm the presence of genetic variability for wt_birth on SSC3 (18.0-20.2 Mb) and for fat deposition traits on SSC6 (133.8-136.0 Mb). Within these regions, fibrosin (FBRS) and myosin light chain, phosphorylatable, fast skeletal muscle (MYLPF) genes could be considered as candidates for the wt_birth signal on SSC3, and the SERPINE1 mRNAbinding protein 1 gene (SERBP1) may be a candidate for the fat deposition trait signals on SSC6.Facultad de Ciencias VeterinariasInstituto de Genética Veterinari

The Impact of Emerging Safety and Effectiveness Evidence on the Use of Physician-administered Drugs: The Case of Bevacizumab for Breast Cancer

Spending on physician-administered drugs is high and uses not approved by the U.S. Food and Drug Administration (FDA) are frequent. While these drugs may be targets of future policy efforts to rationalize use, little is known regarding how physicians respond to emerging safety and effectiveness evidence

Refining genomewide association for growth and fat deposition traits in an F₂ pig population

The identification of genomic regions that affect additive genetic variation and contain genes involved in controlling growth and fat deposition has enormous impact in the farm animal industry (e.g., carcass merit and meat quality). Therefore, a genomewide association study was implemented in an F₂ pig population using a 60,000 SNP marker panel for traits related to growth and fat deposition. Estimated genomic EBV were linearly transformed to calculate SNP effects and to identify genomic positions possibly associated with the genetic variability of each trait. Genomic segments were then defined considering the markers included in a region 1 Mb up- and downstream from the SNP with the smallest -value and a false discovery rate < 0.05 for each trait. The significance for each 2-Mb segment was tested using the Bonferroni correction. Significant SNP were detected on SSC2, SSC3, SSC5, and SSC6, but 2-Mb segment significant effects were observed on SSC3 for weight at birth (wt_birth) and on SSC6 for 10th-rib backfat and last-rib backfat measured by ultrasound at different ages. Furthermore, a 6-Mb segment on SSC6 was also considered because the 2-Mb segments for 10 different fat deposition traits were overlapped. Although the segment effects for each trait remain significant, the proportion of additive variance explained by this larger segment was slightly smaller in some traits. In general, the results confirm the presence of genetic variability for wt_birth on SSC3 (18.0-20.2 Mb) and for fat deposition traits on SSC6 (133.8-136.0 Mb). Within these regions, fibrosin (FBRS) and myosin light chain, phosphorylatable, fast skeletal muscle (MYLPF) genes could be considered as candidates for the wt_birth signal on SSC3, and the SERPINE1 mRNAbinding protein 1 gene (SERBP1) may be a candidate for the fat deposition trait signals on SSC6.Facultad de Ciencias VeterinariasInstituto de Genética Veterinari

Imaging Mercury's polar deposits during MESSENGER's low‐altitude campaign

Images obtained during the low‐altitude campaign in the final year of the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) mission provide the highest‐spatial‐resolution views of Mercury's polar deposits. Images for distinct areas of permanent shadow within 35 north polar craters were successfully captured during the campaign. All of these regions of permanent shadow were found to have low‐reflectance surfaces with well‐defined boundaries. Additionally, brightness variations across the deposits correlate with variations in the biannual maximum surface temperature across the permanently shadowed regions, supporting the conclusion that multiple volatile organic compounds are contained in Mercury's polar deposits, in addition to water ice. A recent large impact event or ongoing bombardment by micrometeoroids could deliver water as well as many volatile organic compounds to Mercury. Either scenario is consistent with the distinctive reflectance properties and well‐defined boundaries of Mercury's polar deposits and the presence of volatiles in all available cold traps

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

Mechanical properties of rubble pile asteroids (Dimorphos, Itokawa, Ryugu, and Bennu) through surface boulder morphological analysis.

Planetary defense efforts rely on estimates of the mechanical properties of asteroids, which are difficult to constrain accurately from Earth. The mechanical properties of asteroid material are also important in the interpretation of the Double Asteroid Redirection Test (DART) impact. Here we perform a detailed morphological analysis of the surface boulders on Dimorphos using images, the primary data set available from the DART mission. We estimate the bulk angle of internal friction of the boulders to be 32.7 ± 2. 5° from our measurements of the roundness of the 34 best-resolved boulders ranging in size from 1.67-6.64 m. The elongated nature of the boulders around the DART impact site implies that they were likely formed through impact processing. Finally, we find striking similarities in the morphology of the boulders on Dimorphos with those on other rubble pile asteroids (Itokawa, Ryugu and Bennu). This leads to very similar internal friction angles across the four bodies and suggests that a common formation mechanism has shaped the boulders. Our results provide key inputs for understanding the DART impact and for improving our knowledge about the physical properties, the formation and the evolution of both near-Earth rubble-pile and binary asteroids