Sex differences in the fetal programming of hypertension

Background: Numerous clinical and experimental studies support the hypothesis that the intrauterine environment is an important determinant of cardiovascular disease and hypertension.Objective: This review examined the mechanisms linking an adverse fetal environment and increased risk for chronic disease in adulthood with an emphasis on gender differences and the role of sex hormones in mediating sexual dimorphism in response to a suboptimal fetal environment.Methods: This review focuses on current findings from the PubMed database regarding animal models of fetal programming of hypertension, sex differences in phenotypic outcomes, and potential mechanisms in offspring of mothers exposed to an adverse insult during gestation. For the years 1988 to 2007, the database was searched using the following terms: fetal programming, intrauterine growth restriction, low birth weight, sex differences, estradiol, testosterone, high blood pressure, and hypertension.Results: The mechanisms involved in the fetal programming of adult disease are multifactorial and include alterations in the regulatory systems affecting the long-tterm control of arterial pressure. Sex differences have been observed in animal models of fetal programming, and recent studies suggest that sex hormones may modulate activity of regulatory systems, leading to a lower incidence of hypertension and vascular dysfunction in females compared with males.Conclusions: Animal models of fetal programming provide critical support for the inverse relationship between birth weight and blood pressure. Experimental models demonstrate that sex differences are observed in the pathophysiologic response to an adverse fetal environment. A role for sex hormone involvement is strongly suggested,with modulation of the renin-angiotensin system as a possible mechanism.     

Getting the Data Flowing: Lessons Learned from Existing Reporting Systems in the Forestry Sector in Indonesia for REDD+ MRV

In the context of REDD+, Measurement, Reporting and Verification (MRV) is one way to manage forest change information. A national carbon and non-carbon database will be used in REDD+ to negotiate compensation schemes with the international community. Much of this data will be collected at the local level, thus a reporting system that can integrate these locally collected data into the national database is crucial. In this paper we compare and draw lessons from three existing local to national reporting systems that include the participation of local communities: 1) the government extension services, 2) the government owned forestry company, and 3) a private logging company in Indonesia, and provide recommendations for REDD+ reporting systems. The results suggest that the main desired conditions for effective data flow are: benefits to motivate local participation, based on contributions to reporting activities; simple data format and reporting procedures to allow local participation in the reporting process, and to support data aggregation at the national level; a facilitator to mediate data aggregation at the village level to ensure data consistency, completeness and accuracy; and a transparent and clear data flow. Under these conditions, continuous, accountable and consistent data flow from the local level will reach the national level where it can be fully utilized.     

P-glycoprotein misfolds in Escherichia coli : evidence against alternating-topology models of the transport cycle

P-glycoprotein (P-gp) is a drug transporter which pumps toxic hydrophobic compounds out of cells, conferring mutidrug resistance. P-gp is predicted to consist of 12 transmembrane &#102 - helices and there is a strong body of experimental support for this model. However, a number of studies, including those on Pgp expressed in E. coli, have reported topologies with fewer than 12 transmembrane &#102 -helices, leading to the hypothesis that the transmembrane topology of the protein changes during function. It is well established that P-gp undergoes conformational changes during its transport cycle and it has been recently shown that these changes are large in magnitude and could, potentially, reflect a changing transmembrane topology. One therefore, reassessed the transmembrane topology of P-gp expressed in E. coli and compared it directly with the topology ofthe protein express ed in mammalian cells. It was clear that the transmembrane topology of the protein was different in the different cell types and that the misfolding of P-gp in E. coli was due to the misrecognition of multiple P-gp sequences as topogenic signals. Thus, the alternative transmembrane topologies reported for P-gp in E. coli are artefacts of the heterologous expression system used, and models based on such data in which the transmembrane topology changes during drug transport are unlikely to be correct. Instead, the large conformational changes observed during the transportcycle are more likely due to changes in &#102 -helix packing.     

For better or worse: Relationship status and body mass index

Recent increases in the incidence of obesity and declines in marriage have prompted policymakers to implement policies to mitigate these trends. This paper examines the link between these two outcomes. There are four hypotheses (selection, protection, social obligation and marriage market) that might explain the relationship between marital status transitions and changes in Body Mass Index (BMI). The selection hypothesis suggests that those with a lower BMI are more likely to be selected into marriage. The protection hypothesis states that married adults will have better physical health as a result of the increased social support and reduced incidence of risky behavior among married individuals. The social obligation hypothesis states that those in relationships may eat more regular meals and/or richer and denser foods due to social obligations which may arise because of marriage. Finally, the marriage market hypothesis indicates that when adults are no longer in the marriage market they may not maintain a healthy BMI because doing so is costly and they are in a stable union—or on the other hand, adults may enhance their prospects in the marriage market by losing weight. Taking advantage of longitudinal data and complete marriage histories in the National Longitudinal Survey of Youth 1979, we estimate individual fixed effects models to examine associations between the change in log BMI and the incidence of overweight and obesity, and changes in relationship status controlling for the effects of aging and other respondent characteristics. We find no support for the marriage protection hypothesis. Rather we find evidence supporting the social obligation and marriage market hypotheses—BMI increases for both men and women during marriage and in the course of a cohabiting relationship. Separate analyses by race and ethnicity reveal substantial differences in the response of BMI to relationship status across these groups.     

Quantum-like interference effect in gene expression: glucose-lactose destructive interference

In this note we illustrate on a few examples of cells and proteins behavior that microscopic biological systems can exhibit a complex probabilistic behavior which cannot be described by classical probabilistic dynamics. These examples support authors conjecture that behavior of microscopic biological systems can be described by quantum-like models, i.e., models inspired by quantum-mechanics. At the same time we do not couple quantum-like behavior with quantum physical processes in bio-systems. We present arguments that such a behavior can be induced by information complexity of even smallest bio-systems, their adaptivity to context changes. Although our examples of the quantum-like behavior are rather simple (lactose-glucose interference in E. coli growth, interference effect for differentiation of tooth stem cell induced by the presence of mesenchymal cell, interference in behavior of PrP(C) and PrP(Sc) prions), these examples may stimulate the interest in systems biology to quantum-like models of adaptive dynamics and lead to more complex examples of nonclassical probabilistic behavior in molecular biology.     

Increased signal complexity is associated with increased mating success

The evolution of complex signals has often been explored by testing multiple functional hypotheses regarding how independent signal components provide selective benefits to offset the costs of their production. In the present study, we take a different approach by exploring the function of complexity per se. We test the hypothesis that increased vibratory signal complexity—based on both proportional and temporal patterning—provides selective benefits to courting male Schizocosa stridulans wolf spiders. In support of this hypothesis, all of our quantified metrics of vibratory signal complexity predicted the mating success of male S. stridulans. The rate of visual signalling, which is mechanistically tied to vibratory signal production, was also associated with mating success. We additionally found evidence that males can dynamically adjust the complexity of their vibratory signalling. Together, our results suggest that complexity per se may be a target of female choice.     

Can Patient Safety Incident Reports Be Used to Compare Hospital Safety? Results from a Quantitative Analysis of the English National Reporting and Learning System Data

Background

The National Reporting and Learning System (NRLS) collects reports about patient safety incidents in England. Government regulators use NRLS data to assess the safety of hospitals. This study aims to examine whether annual hospital incident reporting rates can be used as a surrogate indicator of individual hospital safety. Secondly assesses which hospital characteristics are correlated with high incident reporting rates and whether a high reporting hospital is safer than those lower reporting hospitals. Finally, it assesses which health-care professionals report more incidents of patient harm, which report more near miss incidents and what hospital factors encourage reporting. These findings may suggest methods for increasing the utility of reporting systems.

Methods

This study used a mix methods approach for assessing NRLS data. The data were investigated using Pareto analysis and regression models to establish which patients are most vulnerable to reported harm. Hospital factors were correlated with institutional reporting rates over one year to examine what factors influenced reporting. Staff survey findings regarding hospital safety culture were correlated with reported rates of incidents causing harm; no harm and death to understand what barriers influence error disclosure.

Findings

5,879,954 incident reports were collected from acute hospitals over the decade. 70.3% of incidents produced no harm to the patient and 0.9% were judged by the reporter to have caused severe harm or death. Obstetrics and Gynaecology reported the most no harm events [OR 1.61(95%CI: 1.12 to 2.27), p<0.01] and pharmacy was the hospital location where most near-misses were captured [OR 3.03(95%CI: 2.04 to 4.55), p<0.01]. Clinicians were significantly more likely to report death than other staff [OR 3.04(95%CI: 2.43 to 3.80) p<0.01]. A higher ratio of clinicians to beds correlated with reduced rate of harm reported [RR = -1.78(95%Cl: -3.33 to -0.23), p = 0.03]. Litigation claims per bed were significantly negatively associated with incident reports. Patient satisfaction and mortality outcomes were not significantly associated with reporting rates. Staff survey responses revealed that keeping reports confidential, keeping staff informed about incidents and giving feedback on safety initiatives increased reporting rates [r = 0.26 (p<0.01), r = 0.17 (p = 0.04), r = 0.23 (p = 0.01), r = 0.20 (p = 0.02)].

Conclusion

The NRLS is the largest patient safety reporting system in the world. This study did not demonstrate many hospital characteristics to significantly influence overall reporting rate. There were no association between size of hospital, number of staff, mortality outcomes or patient satisfaction outcomes and incident reporting rate. The study did show that hospitals where staff reported more incidents had reduced litigation claims and when clinician staffing is increased fewer incidents reporting patient harm are reported, whilst near misses remain the same. Certain specialties report more near misses than others, and doctors report more harm incidents than near misses. Staff survey results showed that open environments and reduced fear of punitive response increases incident reporting. We suggest that reporting rates should not be used to assess hospital safety. Different healthcare professionals focus on different types of safety incidents and focusing on these areas whilst creating a responsive, confidential learning environment will increase staff engagement with error disclosure.     

Actin Cytoskeletal Organization in Drosophila Germline Ring Canals Depends on Kelch Function in a Cullin-RING E3 Ligase

The Drosophila Kelch protein is required to organize the ovarian ring canal cytoskeleton. Kelch binds and cross-links F-actin in vitro, and it also functions with Cullin 3 (Cul3) as a component of a ubiquitin E3 ligase. How these two activities contribute to cytoskeletal remodeling in vivo is not known. We used targeted mutagenesis to investigate the mechanism of Kelch function. We tested a model in which Cul3-dependent degradation of Kelch is required for its function, but we found no evidence to support this hypothesis. However, we found that mutant Kelch deficient in its ability to interact with Cul3 failed to rescue the kelch cytoskeletal defects, suggesting that ubiquitin ligase activity is the principal activity required in vivo. We also determined that the proteasome is required with Kelch to promote the ordered growth of the ring canal cytoskeleton. These results indicate that Kelch organizes the cytoskeleton in vivo by targeting a protein substrate for degradation by the proteasome.     

Social complexity as a proximate and ultimate factor in communicative complexity

The 'social complexity hypothesis' for communication posits that groups with complex social systems require more complex communicative systems to regulate interactions and relations among group members. Complex social systems, compared with simple social systems, are those in which individuals frequently interact in many different contexts with many different individuals, and often repeatedly interact with many of the same individuals in networks over time. Complex communicative systems, compared with simple communicative systems, are those that contain a large number of structurally and functionally distinct elements or possess a high amount of bits of information. Here, we describe some of the historical arguments that led to the social complexity hypothesis, and review evidence in support of the hypothesis. We discuss social complexity as a driver of communication and possible causal factor in human language origins. Finally, we discuss some of the key current limitations to the social complexity hypothesis-the lack of tests against alternative hypotheses for communicative complexity and evidence corroborating the hypothesis from modalities other than the vocal signalling channel.     

Genes involved in copper homeostasis in Escherichia coli

Recently, genes for two copper-responsive regulatory systems were identified in the Escherichia coli chromosome. In this report, data are presented that support a hypothesis that the putative multicopper oxidase CueO and the transenvelope transporter CusCFBA are involved in copper tolerance in E. coli.     

Alternative mating strategies in a desert grasshopper: evidence of density-dependence

Field observations revealed that, on a given day, male mating behaviour in a population of the grasshopper Ligurotettix coquilletti ranged from little or no stridulation (inactive) to relatively persistent singing (active signalling). Inactive males were usually located in the territories of active signallers. Actively signalling male achieved more matings, and also more frequently approached and mounted females in incidents terminating in the male departing the female without copulating. Individuals switched between inactive and actively-signalling behaviour during their adult lives, and males that were usually active signallers achieved greater lifetime mating success. Thus, we obtained no evidence to support the hypothesis that variation in mating behaviour was maintained by negative frequency-dependent selection. By comparing the behaviour of males in two field plots maintained at different population densities, however, we found that high density was directly related to a higher incidence of inactive behaviour. Males perched on creosote (Larrea tridentata) bushes (their host plant), and certain bushes. Mating behaviour was independent of body size and, while young (<7 days old) males tended to be inactive, neither age nor the time of adult maturation during the season could fully account for the incidence of inactive behaviour among males. Instead, we suggest that the adoption of inactive behaviour resulted partly from aggressive encounters between males.     

Control of pancreatic β-cell fate by insulin signaling: The sweet spot hypothesis

Diabetes results from an absolute or relative deficiency in functional pancreatic &beta;-cell mass. Over the past few years, there has been renewed interest in the role of insulin itself in the regulation of &beta;-cell fate. Numerous animal models point to a critical role for &beta;-cell insulin signaling in the survival and proliferation of pancreatic &beta;-cells. In the present article, we review new studies that elucidate the mechanism by which insulin exerts anti-apoptotic and pro-mitogenic effects on &beta;-cells. In particular, we highlight the emerging role for Raf-1 kinase in autocrine insulin signaling and &beta;-cell fate decisions. We also discuss provocative evidence that the relationship between the dose of insulin and the birth and death of &beta;-cells is not linear. We propose a new hypothesis based on these findings, called the ‘sweet spot’ hypothesis, that can explain how both upward and downward deviations from normal levels of autocrine/paracrine insulin signaling might play an important role in the pathogenesis of type 1 diabetes and type 2 diabetes. We also highlight the key experiments that are required to further test this hypothesis.     

The Effect of Geography and Citizen Behavior on Motor Vehicle Deaths in the United States

Death due to motor vehicle collisions (MVCs) remains a leading cause of death in the US and alcohol plays a prominent role in a large proportion of these fatalities nationwide. Rates for these incidents vary widely among states and over time. Here, we explore the extent to which driving volume, alcohol consumption, legislation, political ideology, and geographical factors influence MVC deaths across states and time. We specify structural equation models for extracting associations between the factors and outcomes for MVC deaths and compute correlation functions of states’ relative geographic and political positions to elucidate the relative contribution of these factors. We find evidence that state-level variation in MVC deaths is associated with time-varying driving volume, alcohol consumption, and legislation. These relationships are modulated by state spatial proximity, whereby neighboring states are found to share similar MVC death rates over the thirty-year observation period. These results support the hypothesis that neighboring states exhibit similar risk and protective characteristics, despite differences in political ideology.