Sexual selection halts the relaxation of protamine 2 among rodents

Sexual selection has been proposed as the driving force promoting the rapid evolutionary changes observed in some reproductive genes including protamines. We test this hypothesis in a group of rodents which show marked differences in the intensity of sexual selection. Levels of sperm competition were not associated with the evolutionary rates of protamine 1 but, contrary to expectations, were negatively related to the evolutionary rate of cleaved- and mature-protamine 2. Since both domains were found to be under relaxation, our findings reveal an unforeseen role of sexual selection: to halt the degree of degeneration that proteins within families may experience due to functional redundancy. The degree of relaxation of protamine 2 in this group of rodents is such that in some species it has become dysfunctional and it is not expressed in mature spermatozoa. In contrast, protamine 1 is functionally conserved but shows directed positive selection on specific sites which are functionally relevant such as DNA-anchoring domains and phosphorylation sites. We conclude that in rodents protamine 2 is under relaxation and that sexual selection removes deleterious mutations among species with high levels of sperm competition to maintain the protein functional and the spermatozoa competitive.     

A study of the anti‐plasmodium activity of angiotensin II analogs

Controlling the dissemination of malaria requires the development of new drugs against its etiological agent, a protozoan of the Plasmodium genus. Angiotensin II and its analog peptides exhibit activity against the development of immature and mature sporozoites of Plasmodium gallinaceum. In this study, we report the synthesis and characterization of angiotensin II linear and cyclic analogs with anti‐plasmodium activity. The peptides were synthesized by a conventional solid‐phase method on Merrifield's resin using the t‐Boc strategy, purified by RP‐HPLC and characterized by liquid chromatography/ESI (+) MS (LC‐ESI(+)/MS), amino acid analysis, and capillary electrophoresis. Anti‐plasmodium activity was measured in vitro by fluorescence microscopy using propidium iodine uptake as an indicator of cellular damage. The activities of the linear and cyclic peptides are not significantly different (p < 0.05). Kinetics studies indicate that the effects of these peptides on plasmodium viability overtime exhibit a sigmoidal profile and that the system stabilizes after a period of 1 h for all peptides examined. The results were rationalized by partial least‐square analysis, assessing the position‐wise contribution of each amino acid. The highest contribution of polar amino acids and a Lys residue proximal to the C‐terminus, as well as that of hydrophobic amino acids in the N‐terminus, suggests that the mechanism underlying the anti‐malarial activity of these peptides is attributed to its amphiphilic character. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.     

Systematic Review and Meta-Analysis of Validation Studies on a Diabetes Case Definition from Health Administrative Records

Objectives

Health administrative data are frequently used for diabetes surveillance. We aimed to determine the sensitivity and specificity of a commonly-used diabetes case definition (two physician claims or one hospital discharge abstract record within a two-year period) and their potential effect on prevalence estimation.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched Medline (from 1950) and Embase (from 1980) databases for validation studies through August 2012 (keywords: “diabetes mellitus”; “administrative databases”; “validation studies”). Reviewers abstracted data with standardized forms and assessed quality using Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. A generalized linear model approach to random-effects bivariate regression meta-analysis was used to pool sensitivity and specificity estimates. We applied correction factors derived from pooled sensitivity and specificity estimates to prevalence estimates from national surveillance reports and projected prevalence estimates over 10 years (to 2018).

Results

The search strategy identified 1423 abstracts among which 11 studies were deemed relevant and reviewed; 6 of these reported sensitivity and specificity allowing pooling in a meta-analysis. Compared to surveys or medical records, sensitivity was 82.3% (95%CI 75.8, 87.4) and specificity was 97.9% (95%CI 96.5, 98.8). The diabetes case definition underestimated prevalence when it was ≤10.6% and overestimated prevalence otherwise.

Conclusion

The diabetes case definition examined misses up to one fifth of diabetes cases and wrongly identifies diabetes in approximately 2% of the population. This may be sufficiently sensitive and specific for surveillance purposes, in particular monitoring prevalence trends. Applying correction factors to adjust prevalence estimates from this definition may be helpful to increase accuracy of estimates.     

[3H]Ketanserin Binding in Human Brain Postmortem

This study aimed at comparing the binding characteristics of [³H]ketanserin, a high-affinity serotonin 2A (5-HT_2A) receptor antagonist, in the prefrontal cortex, hippocampus and striatum of human brain post-mortem. The results indicated the presence of a single population of binding sites in all the regions investigated, with no statistical difference in maximum binding capacity (B_max) or dissociation constant (K_d) values. The pharmacological profile of [³H]ketanserin binding was consistent with the labeling of the 5-HT_2A receptor, since it revealed a competing drug potency ranking of ketanserin = spiperone > clozapine = haloperidol > methysergide > mesulergine > 5-HT. In conclusion, the 5-HT_2A receptor, as labeled by [³H]ketanserin, would seem to consist of a homogenous population of binding sites and to be equally distributed in human prefronto-cortical, limbic and extrapyramidal structures.     

Apyrases (nucleoside triphosphate-diphosphohydrolases) play a key role in growth control in Arabidopsis

Expression of two Arabidopsis (Arabidopsis thaliana) apyrase (nucleoside triphosphate-diphosphohydrolase) genes with high similarity, APY1 and APY2, was analyzed during seedling development and under different light treatments using beta-glucuronidase fusion constructs with the promoters of both genes. As evaluated by beta-glucuronidase staining and independently confirmed by other methods, the highest expression of both apyrases was in rapidly growing tissues and/or tissues that accumulate high auxin levels. Red-light treatment of etiolated seedlings suppressed the protein and message level of both apyrases at least as rapidly as it inhibited hypocotyl growth. Adult apy1 and apy2 single mutants had near-normal growth, but apy1apy2 double-knockout plants were dwarf, due primarily to reduced cell elongation. Pollen tubes and etiolated hypocotyls overexpressing an apyrase had faster growth rates than wild-type plants. Growing pollen tubes released ATP into the growth medium and suppression of apyrase activity by antiapyrase antibodies or by inhibitors simultaneously increased medium ATP levels and inhibited pollen tube growth. These results imply that APY1 and APY2, like their homologs in animals, act to reduce the concentration of extracellular nucleotides, and that this function is important for the regulation of growth in Arabidopsis.     

Chronic Kidney Disease and Diabetic Retinopathy in Patients with Type 2 Diabetes

Purpose

To explore the relationship between chronic kidney disease (CKD) and diabetic retinopathy (DR) in a representative population of type 2 diabetes mellitus (DM2) patients in Catalonia (Spain).

Methods

This was a population-based, cross-sectional study. A total of 28,344 patients diagnosed with DM2 who had recorded ophthalmologic and renal functional examinations were evaluated. Data were obtained from a primary healthcare electronic database of medical records. CKD was defined as an estimated glomerular filtration ratio (eGFR) of <60 ml/min/1.73m² and/or urine albumin to creatinine ratio (UACR) ≥30 mg/g. DR was categorized as non-vision threatening diabetic retinopathy and vision threatening diabetic retinopathy.

Results

CKD was associated with a higher rate of DR [OR], 95% confidence interval [CI], 1.5 (1.4–1.7). When we analyzed the association between different levels of UACR and DR prevalence observed that DR prevalence rose with the increase of UACR levels, and this association was significant from UACR values ≥10 mg/g, and increased considerably with UACR values ≥300mg/g (Odds ratio [OR], 95% confidence interval [CI], 2.0 (1.6–2.5). This association was lower in patients with eGFR levels 44 to 30 mL/min/1.73m² [OR], 95% confidence interval [CI], 1.3 (1.1–1.6).

Conclusions

These results show that CKD, high UACR and/or low eGFR, appear to be associated with DR in this DM2 population.     

Dental trait expression at the enamel-dentine junction of lower molars in extant and fossil hominoids

Discrete dental traits are used as proxies for biological relatedness among modern human populations and for alpha taxonomy and phylogeny reconstruction within the hominin clade. We present a comparison of the expression of lower molar dental traits (cusp 6, cusp 7, trigonid crest pattern, and protostylid) at the enamel-dentine junction (EDJ) in a variety of extant and fossil hominoid taxa, in order to assess the contribution of the EDJ to the morphology of these traits at the outer enamel surface (OES). Molars (n=44) were imaged nondestructively using high-resolution microCT, and three-dimensional surface models of the EDJ and OES were created to compare trait expression at each surface. Our results indicate that these dental traits originate at the EDJ, and that the EDJ is primarily responsible for their degree of expression at the OES. Importantly, variable trait morphology at the EDJ (often not easily recognizable at the OES) indicates that different developmental processes can produce traits that appear similar at the enamel surface, suggesting caution in intra- and intertaxonomic comparisons. The results also highlight the importance of the EDJ for understanding the morphological development of discrete traits, and for establishing graded scales of variation to compare trait frequency among groups for the purpose of taxonomic and/or phylogenetic analysis. Finally, this study demonstrates that imaging the EDJ of both worn and unworn fossil hominin teeth provides a novel source of information about tooth development and variation in crown morphology.