Recent evolutionary history of American Onchocerca volvulus, based on analysis of a tandemly repeated DNA sequence family

Polymerase chain reaction (PCR) products were characterized for a repeated sequence family (designated "O-150") of the human filarial parasite Onchocerca volvulus. In phylogenetic inferences, the O-150 sequences clustered into closely related groups, suggesting that concerted evolution maintains sequence homology in this family. Using a novel mathematical model based on a nested application of an analysis of variance, we demonstrated that African rainforest and savannah strain parasite populations are significantly different. In contrast, parasites collected in the New World are indistinguishable from African savannah strains of O. volvulus. This finding supports the hypothesis that onchocerciasis was recently introduced into the New World, possibly as a result of the slave trade.      

Gene 33/RALT is induced by hypoxia in cardiomyocytes, where it promotes cell death by suppressing phosphatidylinositol 3-kinase and extracellular signal-regulated kinase survival signaling

Ischemia in the heart deprives cardiomyocytes of oxygen, triggering cell death (myocardial infarction). Ischemia and its cell culture model, hypoxia, elicit a stress response program that contributes to cardiomyocyte death; however, the molecular components required to promote this process remain nebulous. Gene 33 is a 50-kDa cytosolic adapter protein that suppresses signaling from receptor Tyr kinases of the epidermal growth factor receptor/ErbB family. Here we show that adenoviral expression of Gene 33 swiftly stimulates cardiomyocyte death coincident with reduced Akt and extracellular signal-regulated kinase (ERK) signaling. Subjecting cardiomyocytes to hypoxia and then reoxygenation induces gene 33 mRNA and Gene 33 protein. RNA interference experiments indicate that endogenous Gene 33 reduces Akt and ERK signaling and is required for maximal hypoxia-induced cardiomyocyte death. Gene 33 levels are also strikingly increased in myocardial ischemic injury and infarction. Our results identify a new role for Gene 33 as a component in the molecular pathophysiology of ischemic injury.     

Gender-specific patterns of left ventricular and myocyte remodeling following myocardial infarction in mice deficient in the angiotensin II type 1a receptor

Left ventricular (LV) remodeling after myocardial infarction (MI) results from hypertrophy of myocytes and activation of fibroblasts induced, in part, by ligand stimulation of the ANG II type 1 receptor (AT1R). The purpose of the present study was to explore the specific role for activation of the AT 1a R subtype in post-MI remodeling and whether gender differences exist in the patterns of remodeling in wild-type and AT 1a R knockout (KO) mice. AT 1a R-KO mice and wild-type littermates underwent coronary ligation to induce MI or sham procedures; echocardiography and hemodynamic evaluation were performed 6 wk later, and LV tissue was harvested for infarct size determination, morphometric measurements, and gene expression analysis. Survival and infarct size were similar among all male and female wild-type and AT 1a R-KO mice. Hemodynamic indexes were also similar except for lower systolic blood pressure in the AT 1a R-KO mice compared with wild-type mice. Male and female wild-type and male AT 1a R-KO mice developed similar increases in LV chamber size, LV mass corrected for body weight (LV/BW), and myocyte cross-sectional area (CSA). However, female AT 1a R-KO mice demonstrated no increase in LV/BW and myocyte CSA post-MI compared with shams. Both male and female wild-type mice demonstrated higher atrial natriuretic peptide (ANP) levels after MI, with female wild types being significantly greater than males. However, male and female AT 1a R-KO mice developed no increase in ANP gene expression with MI despite an increase in LV mass and myocyte size in males. These data support that gender-specific patterns of LV and myocyte hypertrophy exist after MI in mice with a disrupted AT 1a R gene, and suggest that myocyte hypertrophy post-MI in females relies, in part, on activation of the AT 1a R. Further work is necessary to explore the potential mechanisms underlying these gender-based differences.     

The effects of contemporary processes in maintaining the genetic structure of western song sparrows (Melospiza melodia)

Historic events and contemporary processes work in concert to create and maintain geographically partitioned variation and are instrumental in the generation of biodiversity. We sought to gain a better understanding of how contemporary processes such as movement and isolation influence the genetic structure of widely distributed vagile species such as birds. Song sparrows (Melospiza melodia) in western North America provide a natural system for examining the genetics of populations that have different patterns of geographic isolation and migratory behavior. We examined the population genetics of 576 song sparrows from 23 populations using seven microsatellite loci to assess genetic differentiation among populations and to estimate the effects of drift and immigration (gene flow) on each population. Sedentary, isolated populations were characterized by low levels of immigration and high levels of genetic drift, whereas those populations less isolated displayed signals of high gene flow and little differentiation from other populations. Contemporary dispersal rates from migratory populations, estimated by assignment test, were higher and occurred over larger distances than dispersal from sedentary populations but were also probably too low to counter the effects of drift in most populations. We suggest that geographic isolation and limited gene flow facilitated by migratory behavior are responsible for maintaining observed levels of differentiation among Pacific coastal song sparrow populations.     

Evidence That Intermittent,Excessive Sugar Intake Causes Endogenous Opioid Dependence

Objective: The goal was to determine whether withdrawal from sugar can cause signs of opioid dependence. Because palatable food stimulates neural systems that are implicated in drug addiction, it was hypothesized that intermittent, excessive sugar intake might create dependency, as indicated by withdrawal signs. Research Methods and Procedures: Male rats were food‐deprived for 12 hours daily, including 4 hours in the early dark, and then offered highly palatable 25% glucose in addition to chow for the next 12 hours. Withdrawal was induced by naloxone or food deprivation. Withdrawal signs were measured by observation, ultrasonic recordings, elevated plus maze tests, and in vivo microdialysis. Results: Naloxone (20 mg/kg intraperitoneally) caused somatic signs, such as teeth chattering, forepaw tremor, and head shakes. Food deprivation for 24 hours caused spontaneous withdrawal signs, such as teeth chattering. Naloxone (3 mg/kg subcutaneously) caused reduced time on the exposed arm of an elevated plus maze, where again significant teeth chattering was recorded. The plus maze anxiety effect was replicated with four control groups for comparison. Accumbens microdialysis revealed that naloxone (10 and 20 mg/kg intraperitoneally) decreased extracellular dopamine (DA), while dose‐dependently increasing acetylcholine (ACh). The naloxone‐induced DA/ACh imbalance was replicated with 10% sucrose and 3 mg/kg naloxone subcutaneously. Discussion: Repeated, excessive intake of sugar created a state in which an opioid antagonist caused behavioral and neurochemical signs of opioid withdrawal. The indices of anxiety and DA/ACh imbalance were qualitatively similar to withdrawal from morphine or nicotine, suggesting that the rats had become sugar‐dependent.     

Host plant specialization driven by sexual selection

We propose a new mechanism based on sexual selection to explain the evolution of diet breadth in insects. More specifically, we show that mate choice in females for certain diet-derived male pheromones can be exploited by maternal effect genes that preferentially place offspring on a specific host plant, resulting in specialization. Our analytical model also suggests that the process is more likely to occur with species that show male-congregating mating strategies, such as lekking and hilltopping. The model offers a new explanation for the similarity between the composition of male lepidopteran pheromones and the chemistry of their host plants and also suggests a novel mechanism of host plant shift. This is the first time that sexual selection has been proposed to drive host plant specialization and the first time that a mechanism with selection acting solely on the adult stage has been shown to be capable of determining larval feeding habits.     

Specialists and Generalists: The Sexual Ecology of the Genome

Sexual antagonism occurs when an allele is beneficial in one sex but costly in the other. Parental antagonism occurs when an allele is beneficial when inherited from one sex but costly when inherited from the other because of fitness interactions among kin. Sexual and parental antagonisms together define four genetic niches within the genome that favor different patterns of gene expression. Natural selection generates linkage disequilibrium among sexually and parentally antagonistic loci with male-beneficial alleles coupled to alleles that are beneficial when inherited from males and female-beneficial alleles coupled to alleles that are beneficial when inherited from females. Linkage disequilibrium also develops between sexually and parentally antagonistic loci and loci that influence sex determination. Genes evolve sex-specific expression to resolve sexual antagonism and evolve imprinted expression to resolve parental antagonism. Sex-specific chromosomes allow a gene to specialize in a single niche.Every diploid individual of a sexually reproducing population is derived from an egg fertilized by a sperm. Therefore, males considered collectively have the same reproductive value as females because half the genes of the next generation will be derived from males and half from females (Kokko et al. 2006). This fundamental symmetry is independent of sex ratio and mating system and applies also to hermaphrodites in male and female roles. Despite their equal stakes in posterity, males and females have evolved distinct morphologies and reproductive strategies as indirect consequences, often very indirect, of the ancient dichotomy between production of larger gametes by one sex and smaller gametes by the other (Queller 1997). Vive la différence!Not only are half the genes of the next generation present in females of the current generation, but half the genes of the current generation were inherited from females. Genes of maternal and paternal origin (hereafter matrigenes and patrigenes) are each transmitted to 50% of the next generation of gametes and resulting offspring. Therefore, matrigenic and patrigenic alleles benefit equally from an individual’s survival and reproduction. This symmetry is broken when organisms interact with kin to whom they are unequally related via their mother and father (Haig 1997; Úbeda and Gardner 2010). Adaptive responses to such asymmetries of relatedness can favor gene expression that is conditional on parental origin. “Imprinted” expression can cause matrigenes and patrigenes to have opposing effects on disputed phenotypes (Haig 2000a; Holman and Kokko 2014).Anatomical, physiological, and behavioral sex differences are thus associated with two selective asymmetries, one obvious (natural selection acts differently on genes in female and male bodies) and the other less obvious (natural selection acts differently on genes of maternal and paternal origin). These asymmetries define orthogonal partitions of the gene pool into pairs of “environments” in which there is niche-specific selection (Fig. 1A). Differential selection in male and female niches reinforces sexual dimorphism by processes of sex-specific adaptation. Differential selection in matrigenic and patrigenic niches can result in imprinted gene expression and molecular adaptations acting at cross-purposes within organisms.Open in a separate windowFigure 1.Sex-related partitions of the gene pool. The gene pool is independently subdivided into female (circles) and male (squares) niches and into matrigenic (pink) and patrigenic (blue) niches. Gene flow between the environments is represented by arrows. Thin arrows represent 50% gene flow in each generation. Thick arrows represent 100% gene flow. (A) Autosomal alleles experience all four environments. (B) Y-linked genes experience only the patrigenic male environment. X-linked genes are excluded from this environment.     

Insensitivity of cardiac phosphofructokinase to adrenergic activation in Zucker rats. A post-receptor defect.

Glyoxal bis(guanylhydrazone), the parent compound of methylglyoxal bis(guanylhydrazone), was synthesized and tested for its ability to inhibit the biosynthesis of polyamines. It was found to be a powerful competitive inhibitor of adenosylmethionine decarboxylase (EC 4.1.1.50), yet the lack of the methyl group at the glyoxal portion increased the apparent Ki value for the enzyme by about 30-fold in comparison with methylglyoxal bis(guanylhydrazone). Glyoxal bis(guanylhydrazone) inhibited diamine oxidase (EC 1.4.3.6) activity as effectively as did methylglyoxal bis(guanylhydrazone). The cellular accumulation curves of glyoxal bis(guanylhydrazone) in L1210 cells were practically superimposable with those of methylglyoxal bis(guanylhydrazone), and the uptake of both compounds was distinctly stimulated by a prior treatment with 2-difluoromethylornithine. The drug decreased the concentration of spermidine in a dose-dependent manner and, in contrast with methylglyoxal bis(guanylhydrazone), without a concomitant accumulation of putrescine. The fact that putrescine concentrations were decreased in cells exposed to glyoxal bis(guanylhydrazone) was, at least in part, attributable to an inhibition of ornithine decarboxylase (EC 4.1.1.17) activity in cells treated with the compound. Under these experimental conditions equivalent concentrations of methylglyoxal bis(guanylhydrazone) [1,1'-[(methylethanediylidine)dinitrilo]diguanidine] elicited large increases in the enzyme activity. When combined with difluoromethylornithine, glyoxal bis(guanylhydrazone) potentiated the growth-inhibitory effect of that drug. Taking into consideration the proven anti-leukaemic activity of glyoxal bis(guanylhydrazone), its effectiveness to inhibit spermidine biosynthesis (without raising the concentration of putrescine) as well as its suitability for combined use with inhibitors of ornithine decarboxylase, this drug is apparently worthy of further testing in tumour-bearing animals, especially in combination with difluoromethylornithine or related inhibitors of ornithine decarboxylase.