The mitochondrial genomes of seed plants are unusually large and vary in size by at least an order of magnitude. Much of this variation occurs within a single family, the Cucurbitaceae, whose genomes ...range from an estimated 390 to 2,900 kb in size. We sequenced the mitochondrial genomes of Citrullus lanatus (watermelon: 379,236 nt) and Cucurbita pepo (zucchini: 982,833 nt)--the two smallest characterized cucurbit mitochondrial genomes--and determined their RNA editing content. The relatively compact Citrullus mitochondrial genome actually contains more and longer genes and introns, longer segmental duplications, and more discernibly nuclear-derived DNA. The large size of the Cucurbita mitochondrial genome reflects the accumulation of unprecedented amounts of both chloroplast sequences (>113 kb) and short repeated sequences (>370 kb). A low mutation rate has been hypothesized to underlie increases in both genome size and RNA editing frequency in plant mitochondria. However, despite its much larger genome, Cucurbita has a significantly higher synonymous substitution rate (and presumably mutation rate) than Citrullus but comparable levels of RNA editing. The evolution of mutation rate, genome size, and RNA editing are apparently decoupled in Cucurbitaceae, reflecting either simple stochastic variation or governance by different factors.
The surface of the asteroid Vesta has prominent near-infrared absorption bands characteristic of a range of pyroxenes, confirming a direct link to the basaltic howardite-eucrite-diogenite class of ...meteorites. Processes active in the space environment produce 'space weathering' products that substantially weaken or mask such diagnostic absorption on airless bodies observed elsewhere, and it has long been a mystery why Vesta's absorption bands are so strong. Analyses of soil samples from both the Moon and the asteroid Itokawa determined that nanophase metallic particles (commonly nanophase iron) accumulate on the rims of regolith grains with time, accounting for an observed optical degradation. These nanophase particles, believed to be related to solar wind and micrometeoroid bombardment processes, leave unique spectroscopic signatures that can be measured remotely but require sufficient spatial resolution to discern the geologic context and history of the surface, which has not been achieved for Vesta until now. Here we report that Vesta shows its own form of space weathering, which is quite different from that of other airless bodies visited. No evidence is detected on Vesta for accumulation of lunar-like nanophase iron on regolith particles, even though distinct material exposed at several fresh craters becomes gradually masked and fades into the background as the craters age. Instead, spectroscopic data reveal that on Vesta a locally homogenized upper regolith is generated with time through small-scale mixing of diverse surface components.
Summary Objective Femoroacetabular Impingement (FAI) and Acetabular Dysplasia are common deformities, which have been implicated as a major cause of hip osteoarthritis (OA). We examined whether these ...subtle deformities of the hip are associated with the development of radiographic OA and total hip replacement (THR) in women. Design A population-based, longitudinal cohort of 1003 women underwent pelvis radiographs at years 2 and 20. Alpha Angle, Triangular Index Height, Lateral Centre Edge (LCE) angle and Extrusion Index were measured. An alpha angle of greater than 65° was defined as Cam-type FAI. Radiographic OA and the presence of a THR were then determined at 20 years. Results Cam-type FAI was significantly associated with the development of radiographic OA. Each degree increase in alpha angle above 65° was associated with an increase in risk of 5% (Odds Ratio (OR) 1.05 95% confidence interval (CI) 1.01–1.09) for radiographic OA and 4% (OR 1.04 95% CI 1.00–1.08) for THR. For Acetabular Dysplasia, each degree reduction in LCE angle below 28° was associated with an increase in risk of 13.0% (OR 0.87 95% CI 0.78–0.96) for radiographic OA and 18% (OR 0.82 95% CI 0.75–0.89) for THR. Conclusions This study demonstrates that Cam-type FAI and mild Acetabular Dysplasia are predictive of subsequent OA and THR in a large female population cohort. These are independent of age, BMI and joint space and significantly improve current predictive models of hip OA development.
In situ
neutron diffraction measurements were completed during tensile and compressive deformation of stainless steel 304L additively manufactured (AM) using a high power directed energy deposition ...process. Traditionally produced wrought 304L material was also studied for comparison. The AM material exhibited roughly 200 MPa higher flow stress relative to the wrought material. Crystallite size, crystallographic texture, dislocation density, and lattice strains were all characterized to understand the differences in the macroscopic mechanical behavior. The AM material’s initial dislocation density was about 10 times that of the wrought material, and the flow strength of both materials obeyed the Taylor equation, indicating that the AM material’s increased yield strength was primarily due to greater dislocation density. Also, a ~50 MPa flow strength tension/compression asymmetry was observed in the AM material, and several potential causes were examined.
Traumatic brain injury initiates several metabolic processes that can exacerbate the injury. There is evidence that hypothermia may limit some of these deleterious metabolic responses.
In a ...randomized, controlled trial, we compared the effects of moderate hypothermia and normothermia in 82 patients with severe closed head injuries (a score of 3 to 7 on the Glasgow Coma Scale). The patients assigned to hypothermia were cooled to 33 degrees C a mean of 10 hours after injury, kept at 32 degrees to 33 degrees C for 24 hours, and then rewarmed. A specialist in physical medicine and rehabilitation who was unaware of the treatment assignments evaluated the patients 3, 6, and 12 months later with the use of the Glasgow Outcome Scale.
The demographic characteristics and causes and severity of injury were similar in the hypothermia and normothermia groups. At 12 months, 62 percent of the patients in the hypothermia group and 38 percent of those in the normothermia group had good outcomes (moderate, mild, or no disabilities). The adjusted risk ratio for a bad outcome in the hypothermia group was 0.5 (95 percent confidence interval, 0.2 to 1.2). Hypothermia did not improve the outcomes in the patients with coma scores of 3 or 4 on admission. Among the patients with scores of 5 to 7, hypothermia was associated with significantly improved outcomes at 3 and 6 months (adjusted risk ratio for a bad outcome, 0.2; 95 percent confidence interval, 0.1 to 0.9 at both intervals), although not at 12 months (risk ratio, 0.3; 95 percent confidence interval, 0.1 to 1.0).
Treatment with moderate hypothermia for 24 hours in patients with severe traumatic brain injury and coma scores of 5 to 7 on admission hastened neurologic recovery and may have improved the outcome.
Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in ...African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans.
A total of 46 representative single-nucleotide polymorphisms (SNPs) in 19 loci that were previously reported in GWAS in Europeans (including FTO and MC4R) were genotyped in 4992 subjects from six African-American cohorts. These SNPs were tested for association with body mass index (BMI) after adjustment for age, gender, disease status and population structure in each cohort. Meta-analysis was conducted to combine the results.
Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1 /ATP2A1 and MC4R, showing significant association at 0.005<P<0.05, and had effect sizes between 0.04 and 0.06 s.d. units (or 0.30 to 0.44 g m(-2)) of BMI for each copy of the BMI-increasing allele. The most significantly associated SNPs (rs9424977, rs3101336 and rs2568958) are located in the NEGR1 gene (P=0.005, 0.020 and 0.019, respectively).
We replicated the association of variants at four loci in six African-American cohorts that demonstrated a consistent direction of association with previous studies of adiposity in Europeans. These loci are all highly expressed in the brain, consistent with an important role for central nervous system processes in weight regulation. However, further comprehensive examination of these regions may be necessary to fine map and elucidate for possible genetic differences between these two populations.
Tumour hypoxia is a microenvironmental factor related to poor response to radiation, chemotherapy, genetic instability, selection for resistance to apoptosis, and increased risk of invasion and ...metastasis. Hypoxia-regulated carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its expression has been correlated with the clinical outcome. The purpose of this study was to investigate the correlation of CA IX expression with outcome in patients with invasive breast cancer. We conducted a retrospective study examining the effects of carbonic anhydrase IX (CA IX) on survival in patients with breast cancer. To facilitate the screening of multiple tissue blocks from each patient, tissue microarrays were prepared containing between two and five representative samples of tumour per patient. Immunohistochemistry was used to examine expression of CA IX in patients with breast cancer. The study includes a cohort of 144 unselected patients with early invasive breast cancer who underwent surgery, and had CA IX expression and follow-up data available for analysis. At the time of analysis, there were 28 deaths and median follow-up of 48 months with 96% of patients having at least 2 years of follow-up. CA IX was negative for 107 patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier survival curves show that survival was superior in the CA IX-negative group with a 2-year survival of 97% for negatives and 83% for positives (log-rank test P=0.01). Allowing for potential prognostic variables in a Cox regression analysis, CA IX remained a significant independent predictor of survival (P=0.035). This study showed in both univariate and multivariate analysis that survival is significantly inferior in patients with tumour expressing CA IX. Prospective studies are underway to investigate this correlation in clinical trial setting.
Objective: Previous studies have replicated the association of variants within FTO (fat mass- and obesity-associated) intron 1 with obesity and adiposity quantitative traits in populations of ...European ancestry. Non-European populations, however, have not been so intensively studied. The goal of this investigation was to examine the association of FTO single-nucleotide polymorphisms (SNPs), prominent in the literature in a multiethnic sample of non-Hispanic White American (n=458), Hispanic American (n=373) and African American (n=288) subjects from the Insulin Resistance Atherosclerosis Study (IRAS). This cohort provides the unique ability to evaluate how variation within FTO influences measures of adiposity and glucose homeostasis in three different ethnicities, which were ascertained and examined using a common protocol. Design: A total of 26 FTO SNPs were genotyped, including those consistently associated in the literature (rs9939609, rs8050136, rs1121980, rs1421085, rs17817449 and rs3751812), and tested for association with adiposity and glucose homeostasis traits. Results: For the adiposity phenotypes, these and other SNPs were associated with body mass index (BMI) in both non-Hispanic Whites (P-values ranging from 0.015 to 0.048) and Hispanic Americans (P-values ranging from 7.1 × 10-6 to 0.027). In Hispanic Americans, four other SNPs (rs8047395, rs10852521, rs8057044 and rs8044769) still showed evidence of association after multiple comparisons adjustment (P-values ranging from 5.0 × 10-5 to 5.2 × 10-4). The historically associated BMI SNPs were not associated in the African Americans, but rs1108102 was associated with BMI (P-value of 5.4 × 10-4) after accounting for multiple comparisons. For glucose homeostasis traits, associations were seen with acute insulin response in non-Hispanic Whites and African Americans. However, all associations with glucose homeostasis measures were no longer significant after adjusting for multiple comparisons. Conclusion: These results replicate the association of FTO intron 1 variants with BMI in non-Hispanic Whites and Hispanic Americans but show little evidence of association in African Americans, suggesting that the effect of FTO variants on adiposity phenotypes shows genetic heterogeneity dependent on ethnicity.
As systematists grapple with assembling the Tree of Life, recent studies have encouraged a genomic-scale approach, obtaining DNA sequence data for entire nuclear, plastid or mitochondrial genomes for ...a few exemplar taxa. Some have proclaimed that this comparative genomic strategy heralds the end of incongruence in phylogeny reconstruction. Although we applaud the use of many genes to resolve phylogenetic patterns, there is a significant caveat. In spite of, or even because of, the abundant data per taxon, whole-genome sequencing for a few exemplars can provide completely resolved and strongly supported, but incorrect, evolutionary reconstructions. We provide a conspicuous example that includes
Amborella, the putative sister of all other extant angiosperms, highlighting the limits of phylogenetics when whole genomes are used but taxon sampling is poor.
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