Genomic Patterns of Gene Evolution.

The bounty of genomic sequence and supporting genomic datasets such as expression data enables study of the genomic patterns of gene evolution. Such studies can address long standing questions in the field of molecular evolution, such as the molecular basis of phenotypic change, the relative contributions of selection and drift, and the origin of new genes. Here, I first examine a genomic dataset of nervous system genes and find, contrary to previous reports, that brain genes as a group have not experienced accelerated evolution in the human lineage. From this finding I infer that widespread changes in protein coding sequence are not responsible for the unique features of the human brain. I also compare the prevalence of positively selected genes in human and chimpanzee on a genome-wide scale. After careful control for the differences in genome sequence quality between human and chimpanzee, I find that, consistent with the predictions of neutral theory given the smaller effective population size in humans compared to chimpanzees, humans have fewer positively selected genes and have experienced less purifying selection as well. Finally, I use simulation based on genomic evolutionary rate patterns in Drosophila to examine phylostratigraphy, a method to infer gene age. I find that the method substantially overestimates the age of young genes and underestimates the age of old genes, especially those that evolve rapidly. Furthermore, spurious correlations can result simply from bias in the measurement of gene age. Taken together, these studies suggest that genomic data can yield previously unattainable insights about the history and process of evolution, but that genomic results must be critically evaluated to ensure they reflect true biology, rather than artifacts of data or method.Ph.D.Ecology and Evolutionary BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/86280/1/mbakewel_1.pd

Deposition of metallic silver from versatile amidinate precursors for use in functional materials

Silver (Ag) amidinate metal organic decomposition precursors of the type: [Ag2((ArN)2C(H))2] (Ar = 2,6-dimethylphenyl (1), 2,6-diethylphenyl (2) and 2,6-diisopropylphenyl (3)) have been used for the first time in the deposition of Ag films on glass with multiple functionalities with potential application in optical/biological sensors or for use in electronic circuitry. Precursors 1–3 were isolated from the reaction of silver acetate with the appropriate ligand in a 1:2 stoichiometry and were characterized by 1H and 13C{1H} NMR, thermal gravimetric analysis and single crystal X-ray diffraction for 2. Single-layer depositions at 200 °C on glass substrates via spin coating produced transparent (>90% transmittance) coatings, with well-defined Ag nanoparticles. Multi-layer depositions at 200 °C on glass had a metallic lustre and were found to be conductive ( ρ = 0.916–1.83 × 10−6 Ωm). All films were strongly adhered and displayed excellent coverage of the substrate. Ag films deposited from 1 to 3 were analysed by grazing incidence X-ray diffraction, X-ray photoelectron spectroscopy, energy-dispersive X-ray analysis and scanning electron microscopy, with optical properties determined by UV-Vis spectroscopy

The effects of chest wall loading on perceptions of fatigue, exercise performance, pulmonary function, and muscle perfusion.

BACKGROUND: Load carriage (LC), which directly affects the chest wall and locomotor muscles, has been suggested to alter the ventilatory and circulatory responses to exercise, leading to increased respiratory muscle work and fatigue. However, studies exploring the impact of LC on locomotion increased internal work, complicating their interpretation. To overcome this issue, we sought to determine the effect of chest wall loading with restriction (CWL + R) on cycling performance, cardiopulmonary responses, microvascular responsiveness, and perceptions of fatigue. METHODS: In a randomized crossover design, 23 young healthy males (22 \ub1 4 years) completed a 5 km cycling time trial (TT) in loaded (CWL + R; tightened vest with 10% body weight) and unloaded conditions. After baseline pulmonary function testing (PFT; forced expiratory volume in 1 s, FEV1; forced vital capacity, FVC), cardiopulmonary indices (HR, heart rate; O2 uptake, VO2; ventilation, VE; tidal volume, VT; and breathing frequency, Bf), rating of perceived exertion (RPE), lactate (BLa), and microvascular responses (oxy-, deoxy-, total hemoglobin; and tissue saturation; StO2) of the vastus lateralis using near infrared spectroscopy were collected during the TT; and PFT was repeated post-exercise. RESULTS: Pre-exercise, CWL + R reduced (p < 0.05) FVC (5.6 \ub1 0.8 versus 5.5 \ub1 0.7 L), FEV1 (4.8 \ub1 0.7 versus 4.7 \ub1 0.6 L), and FEV1/FVC (0.9 \ub1 0.1 versus 0.8 \ub1 0.1). CWL + R modified power output (PO) over time (interaction, p = 0.02), although the 5 km time (461 \ub1 24 versus 470 \ub1 27 seconds), VT (3.0 \ub1 0.3 versus 2.8 \ub1 0.8 L), Bf, VE, HR, VO2, microvascular and perceptual (visual analog scale, or VAS, and RPE) responses were unchanged (p > 0.05). CWL + R increased (p < 0.05) the average BLa (7.6 \ub1 2.6 versus 8.6 \ub1 3 mmol/L). CONCLUSIONS: Modest CWL + R negatively affects pre-exercise pulmonary function, modifies cycling power output over time, and increases lactate production during a 5 km cycling trial, although the cardiorespiratory, microvascular, and perceptual responses were unaffected

Reversible Alkene Binding and Allylic C-H Activation with an Aluminum(I) Complex

The monomeric molecular aluminium(I) complex 1 [{(ArNCMe)2CH}Al] (Ar = 2,6-di-iso-propylphenyl) reacts with a series of terminal and strained alkenes including ethylene, propylene, allylbenzene and norbornene to form alkene bound products. Remarkably all these reactions are reversible under mild conditions (298–353 K) with alkene binding being disfavoured at higher temperatures due to the positive reaction entropy. Van't Hoff analyses have allowed quantification of the binding events with Image ID:c8sc04865g-t1.gif. Calculations and single crystal X-ray diffraction studies are consistent with the alkene bound species being metallocyclopropane complexes. Alkene binding involves a reversible redox process with changes from the +1 to +3 aluminium oxidation state. Under more forcing conditions the metallocyclopropane complexes undergo non-reversible allylic C–H bond activation to generate aluminium(III) allyl hydride complexes. This represents a rare example of redox-based main group reactivity in which reversible substrate binding is followed by a further productive bond breaking event. Analysis of the mechanism reveals a reaction network in which alkene dissociation and reformation of 1 is required for allylic C–H activation, a realisation that has important implications for the long-term goal of developing redox-based catalytic cycles with main group compounds

Potential for substitution of geothermal energy at domestic defense installations and White Sands Missile Range

Geothermal resources that might provide substitute energy at any of 76 defense installations are identified and evaluated. The geologic characteristics and related economics of potential geothermal resources located at or near the 76 installations were estimated. The geologic assessment identified 18 installations with possible geothermal resources and 4 Atlantic Coastal Plain resource configurations that represented the alternatives available to East Coast bases. These 18 locations and 4 resource configurations, together with 2 possible resources at the White Sands Missile Range and a potential resource at Kings Bay, Georgia, were examined to determine the relative economics of substituting potential geothermal energy for part or all of the existing oil, gas, and electrical energy usage. Four of the military installations - Mountain Home, Norton, Hawthorne, and Sierra - appear to be co-located with possible geothermal resources which, if present, might provide substitute energy at or below current market prices for oil. Six additional locations - Ellsworth, Luke, Williams, Bliss, Fallon, and Twentynine Palms - could become economically attractive under certain conditions. No geothermal resource was found to be economically competitive with natural gas at current controlled prices. Generation of electric power at the locations studied is estimated to be uneconomic at present

Estimating the risk of mortality attributable to recent late HIV diagnosis following admission to the intensive care unit: A single-centre observational cohort study

OBJECTIVES: Despite improvements in survival of people with HIV admitted to the intensive care unit (ICU), late diagnosis continues to contribute to in-ICU mortality. We quantify the population attributable fraction (PAF) of in-ICU mortality for recent late diagnosis among people with HIV admitted to a London ICU. METHODS: Index ICU admissions among people with HIV were considered from 2000 to 2019. Recent late diagnosis was a CD4 T-cell count < 350 cells/μL and/or AIDS-defining illness at/within 6 months prior to ICU admission. Univariate comparisons were conducted using Wilcoxon rank-sum/Cochran-Armitage/χ2 /Fisher's exact tests. We used Poisson regression (robust standard errors) to estimate unadjusted/adjusted (age, sex, calendar year of ICU admission) risk ratios (RRs) and regression standardization to estimate the PAF. RESULTS: In all, 207 index admissions were included [median (interquartile range) age: 46 (38-53) years; 72% male]; 58 (28%) had a recent late diagnosis, all of whom had a CD4 count < 350 cells/μL, and 95% had advanced HIV (CD4 count < 200 cells/μL and/or AIDS at admission) as compared with 57% of those who did not have a recent late diagnosis (p < 0.001). In-ICU mortality was 27% (55/207); 38% versus 22% in those who did and did not have a recent late diagnosis, respectively (p = 0.02). Recent late diagnosis was independently associated with increased in-ICU mortality risk (adjusted RR = 1.75) (95% confidence interval: 1.05-2.91), with 17.08% (16.04-18.12%) of deaths being attributable to this. CONCLUSIONS: There is a need for improved public health efforts focused on HIV testing and reporting of late diagnosis to better understand potentially missed opportunities for earlier HIV diagnosis in healthcare services