Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns

Mitochondria play an integral role in ATP production in cells and are involved in glucose metabolism and insulin secretion, suggesting that variants in the mitochondrial genome may contribute to diabetes susceptibility. In a study of Finnish families ascertained for type 2 diabetes mellitus (T2DM), we genotyped single nucleotide polymorphisms (SNPs) based on phylogenetic networks. These SNPs defined eight major haplogroups and subdivided groups H and U, which are common in Finns. We evaluated association with both diabetes disease status and up to 14 diabetes-related traits for 762 cases, 402 non-diabetic controls, and 465 offspring of genotyped females. Haplogroup J showed a trend toward association with T2DM affected status (OR 1.69, P =0.056) that became slightly more significant after excluding cases with affected fathers (OR 1.77, P =0.045). We also genotyped non-haplogroup-tagging SNPs previously reported to show evidence for association with diabetes or related traits. Our data support previous evidence for association of T16189C with reduced ponderal index at birth and also show evidence for association with reduced birthweight but not with diabetes status. Given the multiple tests performed and the significance levels obtained, this study suggests that mitochondrial genome variants may play at most a modest role in glucose metabolism in the Finnish population. Furthermore, our data do not support a reported maternal inheritance pattern of T2DM but instead show a strong effect of recall bias.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47596/1/439_2005_Article_46.pd

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

The Importance of Building Relationships with Students Post Remote Learning

Strong bonds created between a teacher and their students within the classroom can greatly help students in a variety of ways. According to the American Psychological Association (2015), the learning process in elementary and secondary classrooms is interpersonal, comprising of both student-teacher and peer relationships. Creating connections within the elementary classroom is vital. Positive student-teacher relationships have been shown to improve student behavior and academic success within the classroom (Kudlats & Brown, 2021). The purpose of this study is to evaluate how relationships between students and their teachers impact students’ learning during a pandemic. To evaluate this topic, I gathered research studies regarding classroom relationships during my student teaching in a fourth-grade classroom. This data consisted of field notes, lesson plans, and student work. I examined my data to look for trends relating to the impact my relationships had on my students in school. Throughout this study, I dove deeper into the importance of building strong relationships with students, especially after students were remote learning

Archaeal Intact Polar Lipids in Polar Waters: A Comparison Between the Amundsen and Scotia Seas

The West Antarctic Ice Sheet (WAIS) is one of the largest potential sources of future sea-level rise, with glaciers draining the WAIS thinning at an accelerating rate over the past 40 years. Due to complexities in calibrating palaeoceanographic proxies for the Southern Ocean, it remains difficult to assess whether similar changes have occurred earlier during the Holocene or whether there is underlying centennial- to millennial-scale forcing in oceanic variability. Archaeal lipid-based proxies, specifically glycerol dialkyl glycerol tetraether (GDGT; e.g. TEX86 and TEXL86), are powerful tools for reconstructing ocean temperature, but these proxies have been shown previously to be difficult to apply to the Southern Ocean. A greater understanding of the parameters that control Southern Ocean GDGT distributions would improve the application of these biomarker proxies and thus help provide a longer-term perspective on ocean forcing of Antarctic ice sheet changes. In this study, we characterised intact polar lipid (IPL)-GDGTs, representing (recently) living archaeal populations in suspended particulate matter (SPM) from the Amundsen Sea and the Scotia Sea. SPM samples from the Amundsen Sea were collected from up to four water column depths representing the surface waters through to Circumpolar Deep Water (CDW), whereas the Scotia Sea samples were collected along a transect encompassing the sub-Antarctic front through to the southern boundary of the Antarctic Circumpolar Current. IPL-GDGTs with low cyclic diversity were detected throughout the water column with high relative abundances of hydroxylated IPL-GDGTs identified in both the Amundsen and Scotia seas. Results from the Scotia Sea show shifts in IPL-GDGT signatures across well-defined fronts of the Southern Ocean. Indicating that the physicochemical parameters of these water masses determine changes in IPL-GDGT distributions. The Amundsen Sea results identified GDGTs with hexose-phosphohexose head groups in the CDW, suggesting active GDGT synthesis at these depths. These results suggest that GDGTs synthesised at CDW depths may be a significant source of GDGTs exported to the sedimentary record and that temperature reconstructions based on TEX86 or TEXL86 proxies may be significantly influenced by the warmer waters of the CDW

Saturated, Suffocated, and Salty: Human Legacies Produce Hot Spots of Nitrogen in Riparian Zones

The compounding effects of anthropogenic legacies for environmental pollution are significant, but not well understood. Here, we show that centennial-scale legacies of milldams and decadal-scale legacies of road salt salinization interact in unexpected ways to produce hot spots of nitrogen (N) in riparian zones. Riparian groundwater and stream water concentrations upstream of two mid-Atlantic (Pennsylvania and Delaware) milldams, 2.4 and 4 m tall, were sampled over a 2 year period. Clay and silt-rich legacy sediments with low hydraulic conductivity, stagnant and poorly mixed hydrologic conditions, and persistent hypoxia in riparian sediments upstream of milldams produced a unique biogeochemical gradient with nitrate removal via denitrification at the upland riparian edge and ammonium-N accumulation in near-stream sediments and groundwaters. Riparian groundwater ammonium-N concentrations upstream of the milldams ranged from 0.006 to 30.6 mgN L−1 while soil-bound values were 0.11–456 mg kg−1. We attribute the elevated ammonium concentrations to ammonification with suppression of nitrification and/or dissimilatory nitrate reduction to ammonium (DNRA). Sodium inputs to riparian groundwater (25–1,504 mg L−1) from road salts may further enhance DNRA and ammonium production and displace sorbed soil ammonium-N into groundwaters. This study suggests that legacies of milldams and road salts may undercut the N buffering capacity of riparian zones and need to be considered in riparian buffer assessments, watershed management plans, and dam removal decisions. Given the widespread existence of dams and other barriers and the ubiquitous use of road salt, the potential for this synergistic N pollution is significant

Technique [Volume 89, Issue 30]

April Fool's web prank well-receivedBreaking the Bubbleby the numbersClough tours campus in annual safety walkCouncil Clippings Senate and HouseEntertainment BriefsFaces at Georgia TechFire victims rebuild with community's helpFor SGA presidential candidates flyers, publicity only part of campaign costsHewitt signs on for six more yearsHistory of April Fool's jokesHorizon's Drawer Boy showcases pleasures of simple lifeMidseason report: Jackets headed in right directionNews BriefsOUR VIEWS Consensus OpinionOUR VIEWS Hot or NotOwings pursues national championship instead of prosPhuong captures SGA presidencyPiedmont hosts annual Dogwood FestivalPolice report few disturbances after gameRare change of heart as profs push back tests, homework for NCAA championship gameRHA seeks funding for newspapersSet education to lofty goals, not moneySports ShortsSwan song recommends campus involvementTech bands battle it out at Couch...Two BitsWillis, Perry reunite in Yards reduxYOUR VIEWS Letters to the Edito