Cardiovascular responses to sustained maximal isometric contractions of the finger flexors

This study investigated cardiovascular responses to 2 min sustained submaximal (20% MVC) and maximal (100% MVC) voluntary isometric contractions of the finger flexors in healthy young women. Cardiovascular variables investigated were: heart rate (f _c), mean arterial pressure ( _a), and stroke volume (SV). Doppler echocardiography was used to estimate SV from measures of aortic diameter (AD) and time-velocity integrals. Preliminary studies indicated that AD did not change significantly after 2 min sustained 100% MVC. Therefore, pre-exercise AD values were used to calculate SV before, during and after exercise. During the 2-min 100% MVC period, f _c and _aincreased significantly during the first 30 s of contraction. f _c then remained constant during the remainder of the 2-min contraction period, while _acontinued to rise. SV did not change significantly during the 100% MVC task but increased significantly during recovery from sustained 100% MVC. The data suggest that the magnitude of cardiovascular responses to isometric exercise is dependent on the specific task performed, and that there is a different pattern of response for f _c, _a, and SV during 20% and 100% MVC tasks. Unlike f _c and _a, SV did not change significantly during isometric exercise, but increased significantly after sustained 100% MVC.     

Vascular responses in forearm and calf to contralateral static exercises

Ten normal subjects performed a 90-s isometric exercise [20, 30, and 40% of maximal voluntary contraction (MVC) of the flexor muscle of the right index finger or quadriceps muscle of the right leg. Contralateral forearm and calf blood flows (strain gauge plethysmography) and arterial blood pressure (auscultation) were measured simultaneously. Each exercise caused a decrease in forearm vascular resistance and a progressive increase in calf resistance. These changes were greatest with the 40% MVC. With finger exercise at 20 and 40% MVC, the percentage decreases in forearm vascular resistance from control were 12.3 and 22.7%, respectively (P less than 0.01). Similar decreases (9.5 and 24.9%, respectively; P less than 0.01) were noted with exercise of the quadriceps muscle. By contrast, the corresponding increases in calf vascular resistance were greater (P less than 0.01) with quadriceps exercise (13.3 and 55.4%, respectively) than with finger exercise (6.0 and 36.0%). Arrest of the circulation to the exercising muscles just before the exercise ended caused an abrupt increase in forearm vascular resistance and a decrease in calf resistance. These studies provide further evidence of the heterogeneity of responses of forearm and calf resistance vessels to certain cardiovascular stimuli.     

Resistance to pirimiphos-methyl in West African Anopheles is spreading via duplication and introgression of the Ace1 locus

Vector population control using insecticides is a key element of current strategies to prevent malaria transmission in Africa. The introduction of effective insecticides, such as the organophosphate pirimiphos-methyl, is essential to overcome the recurrent emergence of resistance driven by the highly diverse Anopheles genomes. Here, we use a population genomic approach to investigate the basis of pirimiphos-methyl resistance in the major malaria vectors Anopheles gambiae and A. coluzzii. A combination of copy number variation and a single non-synonymous substitution in the acetylcholinesterase gene, Ace1, provides the key resistance diagnostic in an A. coluzzii population from Côte d’Ivoire that we used for sequence-based association mapping, with replication in other West African populations. The Ace1 substitution and duplications occur on a unique resistance haplotype that evolved in A. gambiae and introgressed into A. coluzzii, and is now common in West Africa primarily due to selection imposed by other organophosphate or carbamate insecticides. Our findings highlight the predictive value of this complex resistance haplotype for phenotypic resistance and clarify its evolutionary history, providing tools to for molecular surveillance of the current and future effectiveness of pirimiphos-methyl based interventions.     

Postural cardiovascular reflexes: comparison of responses of forearm and calf resistance vessels

Simultaneous measurements were made of changes in vascular resistance in the forearm and calf in response to moving from supine to sitting or to head-down tilt. The subjects were healthy male volunteers, 21-63 yr. Blood flows were measured by venous occlusion plethysmography using mercury-in-Silastic strain-gauges. The gauges were maintained at the same level relative to the heart during the postural changes. Arterial blood pressure was measured by auscultation; heart rate was counted from the plethysmograms. Changing from supine to sitting caused a decrease in forearm blood flow from 4.13 +/- 0.14 to 2.16 +/- 0.19 ml.100 ml-1.min-1. Corresponding calf flows were 4.21 +/- 0.32 and 4.40 +/- 0.59 ml.100 ml-1.min-1. There was no change in mean arterial blood pressure, and heart rate increased by 8.0 +/- 1.5 beats/min. Arrest of the circulation of both legs with occlusion cuffs on the thighs before sitting, to prevent pooling of blood in them, reduced the degree of forearm vasoconstriction. Neck suction (40 Torr) during sitting, to oppose the decrease in transmural pressure at the carotid sinuses, inhibited the vasoconstriction. During a 30 degrees head-down tilt, there was a dilatation of forearm but not of calf resistance vessels. A Valsalva maneuver caused a similar constriction of both vascular beds. Thus, when changes in vascular resistance in forearm and calf are compared, the major reflex adjustments to changes in posture take place in the forearm.     

Contemporary evolution of resistance at the major insecticide target site gene Ace‐1 by mutation and copy number variation in the malaria mosquito Anopheles gambiae

Functionally constrained genes are ideal insecticide targets because disruption is often fatal, and resistance mutations are typically costly. Synaptic acetylcholinesterase (AChE) is an essential neurotransmission enzyme targeted by insecticides used increasingly in malaria control. In Anopheles and Culex mosquitoes, a glycine–serine substitution at codon 119 of the Ace‐1 gene confers both resistance and fitness costs, especially for 119S/S homozygotes. G119S in Anopheles gambiae from Accra (Ghana) is strongly associated with resistance, and, despite expectations of cost, resistant 119S alleles are increasing significantly in frequency. Sequencing of Accra females detected only a single Ace‐1 119S haplotype, whereas 119G diversity was high overall but very low at non‐synonymous sites, evidence of strong purifying selection driven by functional constraint. Flanking microsatellites showed reduced diversity, elevated linkage disequilibrium and high differentiation of 119S, relative to 119G homozygotes across up to two megabases of the genome. Yet these signals of selection were inconsistent and sometimes weak tens of kilobases from Ace‐1. This unexpected finding is attributable to apparently ubiquitous amplification of 119S alleles as part of a large copy number variant (CNV) far exceeding the size of the Ace‐1 gene, whereas 119G alleles were unduplicated. Ace‐1 CNV was detectable in archived samples collected when the 119S allele was rare in Ghana. Multicopy amplification of resistant alleles has not been observed previously and is likely to underpin the recent increase in 119S frequency. The large CNV compromised localization of the strong selective sweep around Ace‐1, emphasizing the need to integrate CNV analysis into genome scans for selection.     

Tropomyosin expression and dynamics in developing avian embryonic muscles

The expression of striated muscle proteins occurs early in the developing embryo in the somites and forming heart. A major component of the assembling myofibrils is the actin-binding protein tropomyosin. In vertebrates, there are four genes for tropomyosin (TM), each of which can be alternatively spliced. TPM1 can generate at least 10 different isoforms including the striated muscle-specific TPM1alpha and TPM1kappa. We have undertaken a detailed study of the expression of various TM isoforms in 2-day-old (stage HH 10-12; 33 h) heart and somites, the progenitor of future skeletal muscles. Both TPM1alpha and TPM1kappa are expressed transiently in embryonic heart while TPM1alpha is expressed in somites. Both RT-PCR and in situ hybridization data suggest that TPM1kappa is expressed in embryonic heart whereas TPM1alpha is expressed in embryonic heart, and also in the branchial arch region of somites, and in the somites. Photobleaching studies of Yellow Fluorescent Protein-TPM1alpha and -TPM1kappa expressed in cultured avian cardiomyocytes revealed that the dynamics of the two probes was the same in both premyofibrils and in mature myofibrils. This was in sharp contrast to skeletal muscle cells in which the fluorescent proteins were more dynamic in premyofibrils. We speculate that the differences in the two muscles is due to the appearance of nebulin in the skeletal myocytes premyofibrils transform into mature myofibrils.     

Reflex constriction of human limb resistance vessels to head-down neck flexion

The effect of head-down neck flexion on forearm and calf blood flow was determined in 10 healthy male subjects. The subject lay prone, with the neck slightly extended and the chin resting on a soft-padded support at the edge of the table. The chin support was then removed, and the subject maximally flexed and lowered the neck. This was followed by return to the initial position. Neck flexion caused a rapid decrease in blood flow in both forearm and calf; at 30 s this averaged 39 and 35%, respectively. The flow in both forearm and calf gradually recovered as the neck flexion was sustained and approached the control values at the end of 10 min. The blood flow at the ankle was unchanged, indicating that the decrease occurred in the skeletal muscles. The arterial blood pressure and heart rate were unchanged; thus the decrease in flow was due to vasoconstriction. The fact that the decrease was evident as soon as the head was lowered indicated that it was nervously mediated. Neither contraction of the flexor muscles of the neck nor venous congestion of the head, in the absence of the head-down position, altered the blood flow. Although the mechanism of the decrease in flow has not been determined, the studies demonstrate that in response to certain stimuli, the resistance vessels in the skeletal muscles of the forearm and calf undergo a similar nervously mediated vasoconstriction.     

Environmental conditions and the performance of free water surface flow constructed wetland: a multivariate statistical approach

During the past three decades, constructed wetlands have become an integral part of the suite of technologies for removing domestic and industrial wastewater contaminants. The use of constructed wetlands has disproportionately focused on domestic and agricultural wastewaters and storm water runoff and less on oil and gas-related produced water. In this context, the cumulative effect of environmental factors on the treatment/removal efficiency of contaminants in produced water is underserved by research. Therefore, this study assessed the effect of environmental factors (temperature, dissolved oxygen, oxidation–reduction potential, and pH) on contaminant removal efficiency in free water surface flow constructed wetland (FWSFCW) using ordinary least squares regression and experimental data from a waste treatment facility in Ghana. The results showed that environmental factors did not systematically vary across the experimental group and control set-up. Generally, the environmental factors explained relatively far less of the variance in contaminant removal efficiency compared with the plant species (Typha latifolia, Ruellia simplex and Alternanthera philoxeroides). Environmental factors cumulatively explained only 1.3%, 16.4%, 22.6%, and 5.6% of the variance in removal efficiency of BOD, COD, oil and grease, and total coliform bacteria, respectively. Temperature was the most important environmental predictor of the removal of BOD and phosphorus whereas DO was most important for removing nitrates and total coliform bacteria. ORP and pH were the most important predictors of COD, and oil and grease, respectively. These findings underscore the complex relationships among environmental factors and contaminant removal efficiency and the need for contaminant management practices and remedial techniques that address these complexities.

     

CYP6 P450 Enzymes and ACE-1 Duplication Produce Extreme and Multiple Insecticide Resistance in the Malaria Mosquito Anopheles gambiae

Malaria control relies heavily on pyrethroid insecticides, to which susceptibility is declining in Anopheles mosquitoes. To combat pyrethroid resistance, application of alternative insecticides is advocated for indoor residual spraying (IRS), and carbamates are increasingly important. Emergence of a very strong carbamate resistance phenotype in Anopheles gambiae from Tiassalé, Côte d''Ivoire, West Africa, is therefore a potentially major operational challenge, particularly because these malaria vectors now exhibit resistance to multiple insecticide classes. We investigated the genetic basis of resistance to the most commonly-applied carbamate, bendiocarb, in An. gambiae from Tiassalé. Geographically-replicated whole genome microarray experiments identified elevated P450 enzyme expression as associated with bendiocarb resistance, most notably genes from the CYP6 subfamily. P450s were further implicated in resistance phenotypes by induction of significantly elevated mortality to bendiocarb by the synergist piperonyl butoxide (PBO), which also enhanced the action of pyrethroids and an organophosphate. CYP6P3 and especially CYP6M2 produced bendiocarb resistance via transgenic expression in Drosophila in addition to pyrethroid resistance for both genes, and DDT resistance for CYP6M2 expression. CYP6M2 can thus cause resistance to three distinct classes of insecticide although the biochemical mechanism for carbamates is unclear because, in contrast to CYP6P3, recombinant CYP6M2 did not metabolise bendiocarb in vitro. Strongly bendiocarb resistant mosquitoes also displayed elevated expression of the acetylcholinesterase ACE-1 gene, arising at least in part from gene duplication, which confers a survival advantage to carriers of additional copies of resistant ACE-1 G119S alleles. Our results are alarming for vector-based malaria control. Extreme carbamate resistance in Tiassalé An. gambiae results from coupling of over-expressed target site allelic variants with heightened CYP6 P450 expression, which also provides resistance across contrasting insecticides. Mosquito populations displaying such a diverse basis of extreme and cross-resistance are likely to be unresponsive to standard insecticide resistance management practices.     

Differential effects of lower body negative pressure on forearm and calf blood flow

Modest degrees of lower body negative pressure (less than 20 mmHg) cause a reflex constriction of forearm resistance vessels attributable to a decrease in activity of cardiopulmonary mechanoreceptors. In the present study, we sought to determine whether the calf vessels respond similarly. Left forearm and right calf blood flows were measured simultaneously by strain-gauge plethysmography in 10 healthy volunteers. Forearm flows decreased significantly from control during negative pressures of 10, 15, or 20 mmHg, whereas calf flows did not decrease significantly until 20 mmHg; at 10, 15, and 20 mmHg, decreases in forearm flow were significantly greater than those of the calf. Similar results were obtained in a second series of experiments in which venous pooling in the right leg during lower body negative pressure was prevented by enclosing it in a boot. At 40 mmHg, or after a Valsalva maneuver, both forearm and calf vessels constricted markedly and to the same degree. It appears that the reflex reduction in blood flow to the skeletal muscles of the limbs resulting from deactivation of the low-pressure intrathoracic mechanoreceptors is directed primarily to the arm.