Evolutionary history of the ADRB2 gene in humans

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A cost-minimization analysis of diuretic-based antihypertensive therapy reducing cardiovascular events in older adults with isolated systolic hypertension

BACKGROUND: Hypertension is among the most common chronic condition in middle-aged and older adults. Approximately 50 million Americans are currently diagnosed with this condition, and more than $18.7 billion is spent on hypertension management, including$3.8 billion for medications. There are numerous pharmacological agents that can be chosen to treat hypertension by physicians in clinical practices. The purpose of this study was to assess the cost of alternative antihypertensive treatments in older adults with isolated systolic hypertension (ISH). METHOD: Using the Systolic Hypertension in the Elderly Program (SHEP) and other data, a cost-minimization analysis was performed. The cost was presented as the cost of number-needed-to treat (NNT) of patients for 5 years to prevent one adverse event associated with cardiovascular disease (CVD). RESULT: It was found that the cost of 5 year NNT to prevent one adverse CVD event ranged widely from $6,843 to$37,408 in older patients with ISH. The incremental cost of the 5 year NNT was lower to treat older patients in the very high CVD risk group relative to patients in the lower CVD risk group, ranging from $456 to$15,511. Compared to the cost of the 5 year NNT of other commonly prescribed antihypertensive drugs, the cost of SHEP-based therapy is the lowest. The incremental costs of the 5 year NNT would be higher if other agents were used, ranging from $6,372 to$38,667 to prevent one CVD event relative to SHEP-based drug therapy. CONCLUSION: Antihypertensive therapy that is diuretic-based and that includes either low-dose reserpine or atenolol is an effective and relatively inexpensive strategy to prevent cardiovascular events in older adults with isolated systolic hypertension. Use of the diuretic-based therapy is the most cost-effective in patients at high risk for developing cardiovascular disease

Neutral Evolution as Diffusion in phenotype space: reproduction with mutation but without selection

The process of `Evolutionary Diffusion', i.e. reproduction with local mutation but without selection in a biological population, resembles standard Diffusion in many ways. However, Evolutionary Diffusion allows the formation of local peaks with a characteristic width that undergo drift, even in the infinite population limit. We analytically calculate the mean peak width and the effective random walk step size, and obtain the distribution of the peak width which has a power law tail. We find that independent local mutations act as a diffusion of interacting particles with increased stepsize.Comment: 4 pages, 2 figures. Paper now representative of published articl

Functional Convergence in Reduced Genomes of Bacterial Symbionts Spanning 200 My of Evolution

The main genomic changes in the evolution of host-restricted microbial symbionts are ongoing inactivation and loss of genes combined with rapid sequence evolution and extreme structural stability; these changes reflect high levels of genetic drift due to small population sizes and strict clonality. This genomic erosion includes irreversible loss of genes in many functional categories and can include genes that underlie the nutritional contributions to hosts that are the basis of the symbiotic association. Candidatus Sulcia muelleri is an ancient symbiont of sap-feeding insects and is typically coresident with another bacterial symbiont that varies among host subclades. Previously sequenced Sulcia genomes retain pathways for the same eight essential amino acids, whereas coresident symbionts synthesize the remaining two. Here, we describe a dual symbiotic system consisting of Sulcia and a novel species of Betaproteobacteria, Candidatus Zinderia insecticola, both living in the spittlebug Clastoptera arizonana. This Sulcia has completely lost the pathway for the biosynthesis of tryptophan and, therefore, retains the ability to make only 7 of the 10 essential amino acids. Zinderia has a tiny genome (208 kb) and the most extreme nucleotide base composition (13.5% G + C) reported to date, yet retains the ability to make the remaining three essential amino acids, perfectly complementing capabilities of the coresident Sulcia. Combined with the results from related symbiotic systems with complete genomes, these data demonstrate the critical role that bacterial symbionts play in the host insect’s biology and reveal one outcome following the loss of a critical metabolic activity through genome reduction

An AT Mutational Bias in the Tiny GC-Rich Endosymbiont Genome of Hodgkinia

The fractional guanine + cytosine (GC) contents of sequenced bacterial genomes range from 13% to 75%. Despite several decades of research aimed at understanding this wide variation, the forces controlling GC content are not well understood. Recent work has suggested that a universal adenine + thymine (AT) mutational bias exists in all bacteria and that the elevated GC contents found in some bacterial genomes is due to genome-wide selection for increased GC content. These results are generally consistent with the low GC contents observed in most strict endosymbiotic bacterial genomes, where the loss of DNA repair mechanisms combined with the population genetic effects of small effective population sizes and decreased recombination should lower the efficacy of selection and shift the equilibrium GC content in the mutationally favored AT direction. Surprisingly, the two smallest bacterial genomes, Candidatus Hodgkinia cicadicola (144 kb) and Candidatus Tremblaya princeps (139 kb), have the unusual combination of highly reduced genomes and elevated GC contents, raising the possibility that these bacteria may be exceptions to the otherwise apparent universal bacterial AT mutational bias. Here, using population genomic data generated from the Hodgkinia genome project, we show that Hodgkinia has a clear AT mutational bias. These results provide further evidence that an AT mutational bias is universal in bacteria, even in strict endosymbionts with elevated genomic GC contents

Bacterial Genes in the Aphid Genome: Absence of Functional Gene Transfer from Buchnera to Its Host

Genome reduction is typical of obligate symbionts. In cellular organelles, this reduction partly reflects transfer of ancestral bacterial genes to the host genome, but little is known about gene transfer in other obligate symbioses. Aphids harbor anciently acquired obligate mutualists, Buchnera aphidicola (Gammaproteobacteria), which have highly reduced genomes (420–650 kb), raising the possibility of gene transfer from ancestral Buchnera to the aphid genome. In addition, aphids often harbor other bacteria that also are potential sources of transferred genes. Previous limited sampling of genes expressed in bacteriocytes, the specialized cells that harbor Buchnera, revealed that aphids acquired at least two genes from bacteria. The newly sequenced genome of the pea aphid, Acyrthosiphon pisum, presents the first opportunity for a complete inventory of genes transferred from bacteria to the host genome in the context of an ancient obligate symbiosis. Computational screening of the entire A. pisum genome, followed by phylogenetic and experimental analyses, provided strong support for the transfer of 12 genes or gene fragments from bacteria to the aphid genome: three LD–carboxypeptidases (LdcA1, LdcA2,ψLdcA), five rare lipoprotein As (RlpA1-5), N-acetylmuramoyl-L-alanine amidase (AmiD), 1,4-beta-N-acetylmuramidase (bLys), DNA polymerase III alpha chain (ψDnaE), and ATP synthase delta chain (ψAtpH). Buchnera was the apparent source of two highly truncated pseudogenes (ψDnaE and ψAtpH). Most other transferred genes were closely related to genes from relatives of Wolbachia (Alphaproteobacteria). At least eight of the transferred genes (LdcA1, AmiD, RlpA1-5, bLys) appear to be functional, and expression of seven (LdcA1, AmiD, RlpA1-5) are highly upregulated in bacteriocytes. The LdcAs and RlpAs appear to have been duplicated after transfer. Our results excluded the hypothesis that genome reduction in Buchnera has been accompanied by gene transfer to the host nuclear genome, but suggest that aphids utilize a set of duplicated genes acquired from other bacteria in the context of the Buchnera–aphid mutualism

Glucose absorption during continuous ambulatory peritoneal dialysis

Glucose absorption during continuous ambulatory peritoneal dialysis. Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are exposed to a continuous infusion of glucose via their peritoneal cavity. We performed studies to quantitate the amount of energy derived from dialysate glucose. Net glucose absorption averaged 182 ± (SD) 61 g/day in 19 studies with a dialysate dextrose concentration of 1.5 or 4.25 g/dl. The amount of glucose absorbed per liter of dialysate (y) varied with the concentration of glucose in dialysate (x), (y = 11.3x - 10.9, r = 0.96), The amount of glucose absorbed per day during a given dialysis regimen was constant. Energy intake from dialysate glucose was 8.4 ± 2.8 kcal/kg of body wt per day, or 12 to 34% of total energy intake. This additional energy may contribute to the anabolic effect reported during CAPD. The ability to vary glucose absorption by altering the dialysate glucose concentration may prove a useful tool to modify energy intake.Absorption de glucose au cours de la dialyse péritonéale continue ambulatoire. Les malades soumis à la dialyse péritonéale continue ambulatoire (CAPD) sont exposés à une administration continue de glucose via leur cavité péritonéale. La quantité d'énergie qui dérive du glucose du dialysat a été quantifiée. L'absorption nette de glucose est en moyenne de 182 ± (SD) 61 g/jour au cours de 19 études avec un dialysat contenant du dextrose, 1,5 ou 4,25 g/dl. La quantité de glucose absorbée par litre de dialysat (y) varie avec la concentration de glucose dans le dialysat (x), (y = 11,3x - 10,9, r = 0,96). La quantité de glucose absorbée par jour pour un type donné de dialyse a été constante. L'entrée d'énergie à partir du glucose du dialysat était de 8,4 ± 2,8 kcal/kg de poids par jour, soit 12 à 34% de l'entrée totale d'énergie. Cette énergie supplémentaire peut contribuer à l'effet anabolique rapporté au cours de CAPD. La possibilité de faire varier l'absorption de glucose en modifiant la concentration de glucose dans le dialysat peut être un moyen utile pour influencer l'entrée d'énergie

Evah Dahkey is a King / music by John H. Cook; words by E. P. Moran and Paul Laurence Dunbar

Cover: caricature photo; Music Supplement of the New York American and Journal. Sunday, October 26, 1902); Publisher: Harry Von Tilzer Music Pub. Co. (Chicago)https://egrove.olemiss.edu/sharris_b/1030/thumbnail.jp

Design and Early In-flight Performance of the Tropical Rainfall Measuring Mission (TRMM) Power Subsystem

Maryland built the spacecraft in-house with four U.S. instruments and one Japanese instrument, the first space flown Precipitation Radar (PR). The TRMM Observatory was successfully launched from Tanegashima Space Center in Japan on an H-2 Expendable Launch Vehicle on November 27, 1997. This paper presents an overview of the TRMM Power System including its design, testing, and in flight performance for the first 70 days. Finally, key lessons learned are presented. The TRMM power system consists of an 18.1 square meter deployed solar array fabricated by TRW with Tecstar GaAs/Ge cells, two (2) Hughes 50 Ampere-Hour (Ah) Super NiCd' batteries, each with 22 Eagle-Picher cells, and three (3) electronics boxes designed to provide power regulation, battery charge control, and command and telemetry interface

Aging and Recovery After Resistance-Exercise-Induced Muscle Damage: Current Evidence and Implications for Future Research

Accepted author manuscript version reprinted, by permission, from Journal of Aging and Physical Activity, 2021, 29(3): 544-551, https://doi.org/10.1123/japa.2020-0201. © Human Kinetics, Inc.Aging is anecdotally associated with a prolonged recovery from resistance training, though current literature remains equivocal. This brief review considers the effects of resistance training on indirect markers of muscle damage and recovery (i.e., muscle soreness, blood markers, and muscle strength) in older males. With no date restrictions, four databases were searched for articles relating to aging, muscle damage, and recovery. Data from 11 studies were extracted for review. Of these, four reported worse symptoms in older compared with younger populations, while two have observed the opposite, and the remaining studies (n = 6) proposed no differences between age groups. It appears that resistance training can be practiced in older populations without concern for impaired recovery. To improve current knowledge, researchers are urged to utilize more ecologically valid muscle-damaging bouts and investigate the mechanisms which underpin the recovery of muscle soreness and strength after exercise in older populations