Strong mitochondrial DNA support for a Cretaceous origin of modern avian lineages

<p>Abstract</p> <p>Background</p> <p>Determining an absolute timescale for avian evolutionary history has proven contentious. The two sources of information available, paleontological data and inference from extant molecular genetic sequences (colloquially, 'rocks' and 'clocks'), have appeared irreconcilable; the fossil record supports a Cenozoic origin for most modern lineages, whereas molecular genetic estimates suggest that these same lineages originated deep within the Cretaceous and survived the K-Pg (Cretaceous-Paleogene; formerly Cretaceous-Tertiary or K-T) mass-extinction event. These two sources of data therefore appear to support fundamentally different models of avian evolution. The paradox has been speculated to reflect deficiencies in the fossil record, unrecognized biases in the treatment of genetic data or both. Here we attempt to explore uncertainty and limit bias entering into molecular divergence time estimates through: (i) improved taxon (<it>n </it>= 135) and character (<it>n = </it>4594 bp mtDNA) sampling; (ii) inclusion of multiple cladistically tested internal fossil calibration points (<it>n </it>= 18); (iii) correction for lineage-specific rate heterogeneity using a variety of methods (<it>n </it>= 5); (iv) accommodation of uncertainty in tree topology; and (v) testing for possible effects of episodic evolution.</p> <p>Results</p> <p>The various 'relaxed clock' methods all indicate that the major (basal) lineages of modern birds originated deep within the Cretaceous, although temporal intraordinal diversification patterns differ across methods. We find that topological uncertainty had a systematic but minor influence on date estimates for the origins of major clades, and Bayesian analyses assuming fixed topologies deliver similar results to analyses with unconstrained topologies. We also find that, contrary to expectation, rates of substitution are not autocorrelated across the tree in an ancestor-descendent fashion. Finally, we find no signature of episodic molecular evolution related to either speciation events or the K-Pg boundary that could systematically mislead inferences from genetic data.</p> <p>Conclusion</p> <p>The 'rock-clock' gap has been interpreted by some to be a result of the vagaries of molecular genetic divergence time estimates. However, despite measures to explore different forms of uncertainty in several key parameters, we fail to reconcile molecular genetic divergence time estimates with dates taken from the fossil record; instead, we find strong support for an ancient origin of modern bird lineages, with many extant orders and families arising in the mid-Cretaceous, consistent with previous molecular estimates. Although there is ample room for improvement on both sides of the 'rock-clock' divide (e.g. accounting for 'ghost' lineages in the fossil record and developing more realistic models of rate evolution for molecular genetic sequences), the consistent and conspicuous disagreement between these two sources of data more likely reflects a genuine difference between estimated ages of (i) stem-group origins and (ii) crown-group morphological diversifications, respectively. Further progress on this problem will benefit from greater communication between paleontologists and molecular phylogeneticists in accounting for error in avian lineage age estimates.</p

Bioinformatic and Genetic Association Analysis of MicroRNA Target Sites in One-Carbon Metabolism Genes

One-carbon metabolism (OCM) is linked to DNA synthesis and methylation, amino acid metabolism and cell proliferation. OCM dysfunction has been associated with increased risk for various diseases, including cancer and neural tube defects. MicroRNAs (miRNAs) are ∼22 nt RNA regulators that have been implicated in a wide array of basic cellular processes, such as differentiation and metabolism. Accordingly, mis-regulation of miRNA expression and/or activity can underlie complex disease etiology. We examined the possibility of OCM regulation by miRNAs. Using computational miRNA target prediction methods and Monte-Carlo based statistical analyses, we identified two candidate miRNA “master regulators” (miR-22 and miR-125) and one candidate pair of “master co-regulators” (miR-344-5p/484 and miR-488) that may influence the expression of a significant number of genes involved in OCM. Interestingly, miR-22 and miR-125 are significantly up-regulated in cells grown under low-folate conditions. In a complementary analysis, we identified 15 single nucleotide polymorphisms (SNPs) that are located within predicted miRNA target sites in OCM genes. We genotyped these 15 SNPs in a population of healthy individuals (age 18–28, n = 2,506) that was previously phenotyped for various serum metabolites related to OCM. Prior to correction for multiple testing, we detected significant associations between TCblR rs9426 and methylmalonic acid (p  =  0.045), total homocysteine levels (tHcy) (p  =  0.033), serum B12 (p < 0.0001), holo transcobalamin (p < 0.0001) and total transcobalamin (p < 0.0001); and between MTHFR rs1537514 and red blood cell folate (p < 0.0001). However, upon further genetic analysis, we determined that in each case, a linked missense SNP is the more likely causative variant. Nonetheless, our Monte-Carlo based in silico simulations suggest that miRNAs could play an important role in the regulation of OCM

Relax "Vitality in Practice" (VIP) project and design of an RCT to reduce the need for recovery in office employees

<p>Abstract</p> <p>Background</p> <p>There is strong evidence to suggest that multiple work-related health problems are preceded by a higher need for recovery. Physical activity and relaxation are helpful in decreasing the need for recovery. This article aims to describe (1) the development and (2) the design of the evaluation of a daily physical activity and relaxation intervention to reduce the need for recovery in office employees.</p> <p>Methods/Design</p> <p>The study population will consist of employees of a Dutch financial service provider. The intervention was systematically developed, based on parts of the Intervention Mapping (IM) protocol. Assessment of employees needs was done by combining results of face-to-face interviews, a questionnaire and focus group interviews. A set of theoretical methods and practical strategies were selected which resulted in an intervention program consisting of Group Motivational Interviewing (GMI) supported by a social media platform, and environmental modifications. The Be Active & Relax program will be evaluated in a modified 2 X 2 factorial design. The environmental modifications will be pre-stratified and GMI will be randomised on department level. The program will be evaluated, using 4 arms: (1) GMI and environmental modifications; (2) environmental modifications; (3) GMI; (4) no intervention (control group). Questionnaire data on the primary outcome (need for recovery) and secondary outcomes (daily physical activity, sedentary behaviour, relaxation/detachment, work- and health-related factors) will be gathered at baseline (T0), at 6 months (T1), and at 12 months (T2) follow-up. In addition, an economic and a process evaluation will be performed.</p> <p>Discussion</p> <p>Reducing the need for recovery is hypothesized to be beneficial for employees, employers and society. It is assumed that there will be a reduction in need for recovery after 6 months and 12 months in the intervention group, compared to the control group. Results are expected in 2013.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): NTR2553</p

Dense sampling of bird diversity increases power of comparative genomics (vol 587, pg 252, 2020)

Publishe

Isolated limb perfusion for unresectable extremity cutaneous squamous cell carcinoma; an effective limb saving strategy

Background: A small minority of patients present with locally advanced cutaneous Squamous Cell Carcinoma (cSCC). The aim of this study was to evaluate the effectiveness of Tumour necrosis factor α (TNF) and melphalan based isolated limb perfusion (TM-ILP) as a limb saving strategy for locally advanced extremity cSCC. Methods: A retrospective search from prospectively maintained databases, at two tertiary referral centers, was performed to identify patients treated with TM-ILP for locally advanced cSSC of an extremity between 2000 and 2015. Results: A total of 30 patients treated with TM-ILP for cSCC were identified, with a median age of 71 years (36–92) and 50% female. Response could not be evaluated in 3 patients. After a median follow up of 25 months, the overall response rate was 81% (n = 22), with 16 patients having a complete response (CR, 59%). A total of 7 patients developed local recurrence, with a median time to recurrence of 9 months (Interquartile Range 7–10). Progressive disease was observed in 5 patients (19%). Limb salvage rate was 80%. The overall 2-year survival was 67%. Conclusions: TM-ILP should be considered as an option in patients with locally advanced cSCC in specialised centers, resulting in a high limb salvage rate

Test 601: John Deere 420/430 C

EXPLANATION OF TEST REPORT: John Deere 420/430 C TEST A: The manufacturer\u27s representative operates the tractor for a minimum of 12 hours using light to heavy drawbar loads in each gear. This serves as a period for limber up, general observation and adjustments. Adjustments that are permissible include valve tappet clearance, breaker ,point gap, spark plug gaps, clutch and others of a similar nature. No new parts or accessories can be installed without having mention made of it in the report. No data\u27 are recorded during this preliminary run except the time that the engine is operated. BELT HORSEPOWER TESTS TEST B: The throttle valve is hdd wide opened and the belt load on the dynamometer is adjusted so that the engine is at the rated speed recommended by the manufacturer. Carburetor, ignition timing and manifold adjustments are all set for maximum engine power. This test is designed to determine maximum belt horsepower of the tractor at ra.te.d speed and to measure fuel consumption at the maximum power on the belt. TEST C: For tractors with carburetors the best fuel economy does not always occur when the engine develops maximum power at rated speed. Test C is intended to allow the manufacturer\u27s representative to select a more economical fuel setting even though there is a slight loss of power. This more practical carburetor setting is used in all later tests except test F. The throttle valve is held wide open and load adjusted to give rated rpm. Tests Band C are the same for diesel tractors, which have an altogether different fuel system. TEST D: The throttle control lever is set so that the governor will maintain rated engine speed when rated load is applied. Rated load is 85% of 100% maximum, as obtained in test B, corrected to standard conditions. This rating is somewhat less than the maximum belt horsepower in order that the operator may have a certain amount of reserve. TEST E: Varying load serves to show the range of engine speeds when the engine is controlled by the governor during the following varied loads of 20 minutes each: rated load, no load, 1/2 rated load, maximum load at wide open throttle valve, 1/4 and 3/4 rated load. The average result of this test shows the average power and fuel consumption. Since the average tractor is subjected to varying loads, these data serve well in predicting fuel consumptionand efficiency of a tractor in general use. Torque, lb-ft at dynamometer, is obtained with wide open throttle and sufficient load is applied to give several readings. DRAWBAR HORSEPOWER TESTS In all drawbar tests the pull exerted by the tractor is transmitted by a hydraulic pressure cylinder to a recording instrument in the test car. All tests are made on the same dirt test course which is maintained by grading, sprinkling and rolling so that it remains very nearly the same throughout the season. The same tires, wheels and weights are used for all tests except J and K. TEST F: A drawbar test, the results of which are used to determine the rated drawbar horsepower in test H. The carburetor is set to develop maximum power as in test B. The rated gear recommended by manufacturer as plow gear is used in this test. The drawbar load is adjusted to give rated engine speed. TEST G: Maximum drawbar horsepower is determined in each gear when the carburetor is set for fuel economy as in test C. The throttle valve is held wide open and the load is applied so that the engine runs at rated engine speed. When operating in low gear it is not uncommon for the tractor to develop less drawbar horsepower than in rated gear because of excessive wheel slippage. When excessive wheel slippage occurs the load is reduced until slippage approaches 16%. When the load is reduced it is necessary to operate the tractor engine at part throttle and control engine speed by governor action. TEST H: Intended to test the ability of the tractor to run continuously for 10 hours at rated drawbar horsepower and to determine the fuel consumption during that time. Rated drawbar horsepower is 75% of 10°% maximum drawbar horsepower (Test F), corrected to standard conditions. When operating at rated load the throttle control lever is set to maintain rated engine speed. This rating is less than maximum drawbar horsepower in order that the operator may have a certain amount of reserve. TEST J: The tractor is operated in rated gear with all added weight removed. This test shows the effect of the removal of added weight on the performance of the tractor when compared with test G. Removal of wheel weights generally increases wheel slippage and decreases drawbar horsepower. TEST K: Similar to test J except that the smallest tires and lightest wheels offered by the manufacturer are used

Diviner Lunar Radiometer observations of cold traps in the Moon's south polar region.

Diviner Lunar Radiometer Experiment surface-temperature maps reveal the existence of widespread surface and near-surface cryogenic regions that extend beyond the boundaries of persistent shadow. The Lunar Crater Observation and Sensing Satellite (LCROSS) struck one of the coldest of these regions, where subsurface temperatures are estimated to be 38 kelvin. Large areas of the lunar polar regions are currently cold enough to cold-trap water ice as well as a range of both more volatile and less volatile species. The diverse mixture of water and high-volatility compounds detected in the LCROSS ejecta plume is strong evidence for the impact delivery and cold-trapping of volatiles derived from primitive outer solar system bodies