Microguards and micromessengers of the genome

The regulation of gene expression is of fundamental importance to maintain organismal function and integrity and requires a multifaceted and highly ordered sequence of events. The cyclic nature of gene expression is known as ‘transcription dynamics’. Disruption or perturbation of these dynamics can result in significant fitness costs arising from genome instability, accelerated ageing and disease. We review recent research that supports the idea that an important new role for small RNAs, particularly microRNAs (miRNAs), is in protecting the genome against short-term transcriptional fluctuations, in a process we term ‘microguarding’. An additional emerging role for miRNAs is as ‘micromessengers’—through alteration of gene expression in target cells to which they are trafficked within microvesicles. We describe the scant but emerging evidence that miRNAs can be moved between different cells, individuals and even species, to exert biologically significant responses. With these two new roles, miRNAs have the potential to protect against deleterious gene expression variation from perturbation and to themselves perturb the expression of genes in target cells. These interactions between cells will frequently be subject to conflicts of interest when they occur between unrelated cells that lack a coincidence of fitness interests. Hence, there is the potential for miRNAs to represent both a means to resolve conflicts of interest, as well as instigate them. We conclude by exploring this conflict hypothesis, by describing some of the initial evidence consistent with it and proposing new ideas for future research into this exciting topic

Risk factors and myocardial infarction in patients with obstructive sleep apnea: impact of β2-adrenergic receptor polymorphisms

BACKGROUND: The increased sympathetic nervous activity in patients with obstructive sleep apnea (OSA) is largely responsible for the high prevalence of arterial hypertension, and it is suggested to adversely affect triglyceride and high-density lipoprotein (HDL) cholesterol levels in these patients. The functionally relevant polymorphisms of the β2-adrenergic receptor (Arg-47Cys/Arg16Gly and Gln27Glu) have been shown to exert modifying effects on these risk factors in previous studies, but results are inconsistent. METHODS: We investigated a group of 429 patients (55 ± 10.7 years; 361 men, 68 women) with moderate to severe obstructive sleep apnea (apnea/hypopnea index (AHI) 29.1 ± 23.1/h) and, on average, a high cardiovascular risk profile (body mass index 31.1 ± 5.6, with hypertension in 60.1%, dyslipidemia in 49.2%, and diabetes in 17.2% of patients). We typed the β2-adrenergic receptor polymorphisms and investigated the five most frequent haplotypes for their modifying effects on OSA-induced changes in blood pressure, heart rate, and lipid levels. The prevalence of cardiovascular risk factors and coronary heart disease (n = 55, 12.8%) and survived myocardial infarction (n = 27, 6.3%) were compared between the genotypes and haplotypes. RESULTS: Multivariate linear/logistic regressions revealed a significant and independent (from BMI, age, sex, presence of diabetes, use of antidiabetic, lipid-lowering, and antihypertensive medication) influence of AHI on daytime systolic and diastolic blood pressure, heart rate, prevalence of hypertension, and triglyceride and HDL levels. The β2-adrenergic receptor genotypes and haplotypes showed no modifying effects on these relationships or on the prevalence of dyslipidemia, diabetes, and coronary heart disease, yet, for all three polymorphisms, heterozygous carriers had a significantly lower relative risk for myocardial infarction (Arg-47Cys: n = 195, odds ratio (OR) = 0.32, P = 0.012; Arg16Gly: n = 197, OR = 0.39, P = 0.031; Gln27Glu: OR = 0.37, P = 0.023). Carriers of the most frequent haplotype (n = 113) (haplotype 1; heterozygous for all three polymorphisms) showed a five-fold lower prevalence of survived myocardial infarction (OR = 0.21, P = 0.023). CONCLUSION: Our study showed no significant modifying effect of the functionally relevant β2-adrenergic receptor polymorphisms on OSA-induced blood pressure, heart rate, or lipid changes. Nevertheless, heterozygosity of these polymorphisms is associated with a lower prevalence of survived myocardial infarction in this group with, on average, a high cardiovascular risk profile

Development and preliminary validation of a Greek-language outpatient satisfaction questionnaire with principal components and multi-trait analyses

BACKGROUND: In the recent years there is a growing interest in Greece concerning the measurement of the satisfaction of patients who are visiting the outpatient clinics of National Health System (NHS) general acute hospitals. The aim of this study is therefore to develop a patient satisfaction questionnaire and provide its preliminary validation. METHODS: A questionnaire in Greek has been developed by literature review, researchers' on the spot observation and interviews. Pretesting has been followed by telephone surveys in two short-term general NHS hospitals in Macedonia, Greece. A proportional stratified random sample of 285 subjects and a second random sample of 100 outpatients, drawn on March 2004, have been employed for the analysis. These have resulted in scale creation via Principal Components Analysis and psychometric testing for internal consistency, test-retest and interrater reliability as well as construct validity. RESULTS: Four summated scales have emerged regarding the pure outpatient component of the patients' visits, namely medical examination, hospital environment, comfort and appointment time. Cronbach's alpha coefficients and Pearson, Spearman and intraclass correlations indicate a high degree of scale reliability and validity. Two other scales -lab appointment time and lab experience- capture the apparently distinct yet complementary visitor experience related to the radiographic and laboratory tests. Psychometric tests are equally promising, however, some discriminant validity differences lack statistical significance. CONCLUSION: The instrument appears to be reliable and valid regarding the pure outpatient experience, whereas more research employing larger samples is required in order to establish the apparent psychometric properties of the complementary radiographic and laboratory-testing process, which is only relevant to about 25% of the subjects analysed here

Hard-Object Feeding in Sooty Mangabeys (Cercocebus atys) and Interpretation of Early Hominin Feeding Ecology

Morphology of the dentofacial complex of early hominins has figured prominently in the inference of their dietary adaptations. Recent theoretical analysis of craniofacial morphology of Australopithecus africanus proposes that skull form in this taxon represents adaptation to feeding on large, hard objects. A modern analog for this specific dietary specialization is provided by the West African sooty mangabey, Cercocebus atys. This species habitually feeds on the large, exceptionally hard nuts of Sacoglottis gabonensis, stereotypically crushing the seed casings using their premolars and molars. This type of behavior has been inferred for A. africanus based on mathematical stress analysis and aspects of dental wear and morphology. While postcanine megadontia, premolar enlargement and thick molar enamel characterize both A. africanus and C. atys, these features are not universally associated with durophagy among living anthropoids. Occlusal microwear analysis reveals complex microwear textures in C. atys unlike those observed in A. africanus, but more closely resembling textures observed in Paranthropus robustus. Since sooty mangabeys process hard objects in a manner similar to that proposed for A. africanus, yet do so without the craniofacial buttressing characteristic of this hominin, it follows that derived features of the australopith skull are sufficient but not necessary for the consumption of large, hard objects. The adaptive significance of australopith craniofacial morphology may instead be related to the toughness, rather than the hardness, of ingested foods

Evolutionary Reconstructions of the Transferrin Receptor of Caniforms Supports Canine Parvovirus Being a Re-emerged and Not a Novel Pathogen in Dogs

Parvoviruses exploit transferrin receptor type-1 (TfR) for cellular entry in carnivores, and specific interactions are key to control of host range. We show that several key mutations acquired by TfR during the evolution of Caniforms (dogs and related species) modified the interactions with parvovirus capsids by reducing the level of binding. These data, along with signatures of positive selection in the TFRC gene, are consistent with an evolutionary arms race between the TfR of the Caniform clade and parvoviruses. As well as the modifications of amino acid sequence which modify binding, we found that a glycosylation site mutation in the TfR of dogs which provided resistance to the carnivore parvoviruses which were in circulation prior to about 1975 predates the speciation of coyotes and dogs. Because the closely-related black-backed jackal has a TfR similar to their common ancestor and lacks the glycosylation site, reconstructing this mutation into the jackal TfR shows the potency of that site in blocking binding and infection and explains the resistance of dogs until recent times. This alters our understanding of this well-known example of viral emergence by indicating that canine parvovirus emergence likely resulted from the re-adaptation of a parvovirus to the resistant receptor of a former host

Female preference for blue in Japan blue guppies (Poecilia reticulata)

Guppies (Poecilia reticulata) are widely used as a model species in mate choice studies. Although native to South America, guppies have been introduced to natural water bodies in disparate regions of the globe. Here, for the first time, we examine guppies from one such introduced population in Japan where males have evolved a predominantly blue color pattern. Previous studies of wild-type guppies have shown blue to play a relatively minor role in the mate choice decisions of females compared to other traits, such as orange, and the importance of blue is not universally supported by all studies. The Japanese population therefore presents an ideal opportunity to re-examine the potential significance of blue as a mate choice cue in guppies. Mate choice experiments, in which female Japan blue guppies were given a choice between pairs of males that differed in their area of blue coloration but were matched for other traits, revealed that females prefer males with proportionately larger amounts of blue in their color patterns. We discuss possible factors, including sexual and ecological selection, which may have led to the evolution of unusually large areas of blue at the expense of other colors in Japan blue guppies. However, further studies are needed to distinguish between these scenarios.Web of Scienc

Variation in the Structure of Bird Nests between Northern Manitoba and Southeastern Ontario

Traits that converge in appearance under similar environmental conditions among phylogenetically independent lineages are thought to represent adaptations to local environments. We tested for convergence in nest morphology and composition of birds breeding in two ecologically different locations in Canada: Churchill in northern Manitoba and Elgin in southeastern Ontario. We examined nests from four families of passerine birds (Turdidae: Turdus, Parulidae: Dendroica, Emberizidae: Passerculus and Fringillidae: Carduelis) where closely related populations or species breed in both locations. Nests of American Robins, Yellow Warblers, and Carduelis finches had heavier nest masses, and tended to have thicker nest-walls, in northern Manitoba compared with conspecifics or congenerics breeding in southeastern Ontario. Together, all species showed evidence for wider internal and external nest-cup diameters in northern Manitoba, while individual species showed varying patterns for internal nest-cup and external nest depths. American Robins, Yellow Warblers, and Carduelis finches in northern Manitoba achieved heavier nest masses in different ways. American Robins increased all materials in similar proportions, and Yellow Warblers and Common Redpolls used greater amounts of select materials. While changes in nest composition vary uniquely for each species, the pattern of larger nests in northern Manitoba compared to southeastern Ontario in three of our four phylogenetically-independent comparisons suggests that birds are adapting to similar selective pressures between locations