A blood based 12-miRNA signature of Alzheimer disease patients

Background

Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples.

Results

We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies.

Conclusions

The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases.     

Ovariectomy and overeating palatable, energy-dense food increase subcutaneous adipose tissue more than intra-abdominal adipose tissue in rats

Background

Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 h after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis.

Methods

In order to study sex differences in the innate immune response, five male and female BALB/c mice were infected intraperitoneally with coxsackievirus B3 (CVB3) or phosphate buffered saline and their spleens were harvested 12 h later for microarray analysis. Gene expression was determined using an Affymetrix Mouse Gene 1.0 ST Array. Significant gene changes were verified by quantitative real-time polymerase chain reaction or ELISA.

Results

During the innate immune response to CVB3 infection, infected males had higher splenic expression of genes which are important in regulating the influx of cholesterol into macrophages, such as phospholipase A₂ (PLA₂) and the macrophage scavenger receptor compared to the infected females. We also observed a higher expression in infected males compared to infected females of squalene synthase, an enzyme used to generate cholesterol within cells, and Cyp2e1, an enzyme important in metabolizing cholesterol and steroids. Infected males also had decreased levels of the translocator protein 18 kDa (TSPO), which binds PLA₂ and is the rate-limiting step for steroidogenesis, as well as decreased expression of the androgen receptor (AR), which indicates receptor activation. Gene differences were not due to increased viral replication, which was unaltered between sexes.

Conclusions

We found that, compared to females, male mice had a greater splenic expression of genes which are important for cholesterol metabolism and activation of the AR at 12 h after infection. Activation of the AR has been linked to increased cardiac hypertrophy, atherosclerosis, myocarditis/DCM and heart failure in male mice and humans.     

HBV infection in relation to consistent condom use: a population-based study in Peru

Background

Data on hepatitis B virus (HBV) prevalence are limited in developing countries. There is also limited information of consistent condom use efficacy for reducing HBV transmission at the population level. The study goal was to evaluate the prevalence and factors associated with HBV infection in Peru, and the relationship between anti-HBc positivity and consistent condom use.

Methods and Findings

Data from two different surveys performed in 28 mid-sized Peruvian cities were analyzed. Participants aged 18–29 years were selected using a multistage cluster sampling. Information was collected through a validated two-part questionnaire. The first part (face-to-face) concerned demographic data, while the second part (self-administered using handheld computers) concerned sexual behavior. Hepatitis B core antibody (anti-HBc) was tested in 7,000 blood samples. Prevalences and associations were adjusted for sample strata, primary sampling units and population weights. Anti-HBc prevalence was 5.0% (95%CI 4.1%–5.9%), with the highest prevalence among jungle cities: 16.3% (95%CI 13.8%–19.1%). In the multivariable analysis, Anti-HBc positivity was directly associated with geographic region (highlands OR = 2.05; 95%CI 1.28–3.27, and jungle OR = 4.86; 95%CI 3.05–7.74; compared to coastal region); and inversely associated with age at sexual debut (OR = 0.90; 95%CI 0.85–0.97). Consistent condom use, evaluated in about 40% of participants, was associated with reduced prevalence (OR = 0.34; 95%CI 0.15–0.79) after adjusting for gender, geographic region, education level, lifetime number of sex partners, age at sexual debut and year of survey.

Conclusion

Residence in highlands or jungle cities is associated with higher anti-HBc prevalences, whereas increasing age at sexual debut were associated with lower prevalences. Consistent condom use was associated with decreased risk of anti-HBc. Findings from this study emphasize the need of primary prevention programs (vaccination) especially in the jungle population, and imply that condom use promotion might be a potential strategy to prevent HBV infection.     

Clandestine induced abortion: prevalence,incidence and risk factors among women in a Latin American country

Background

Clandestine induced abortions are a public health problem in many developing countries where access to abortion services is legally restricted. We estimated the prevalence and incidence of, and risk factors for, clandestine induced abortions in a Latin American country.

Methods

We conducted a large population-based survey of women aged 18–29 years in 20 cities in Peru. We asked questions about their history of spontaneous and induced abortions, using techniques to encourage disclosure.

Results

Of 8242 eligible women, 7992 (97.0%) agreed to participate. The prevalence of reported induced abortions was 11.6% (95% confidence interval [CI] 10.9%– 12.4%) among the 7962 women who participated in the survey. It was 13.6% (95% CI 12.8%– 14.5%) among the 6559 women who reported having been sexually active. The annual incidence of induced abortion was 3.1% (95% CI 2.9%– 3.3%) among the women who had ever been sexually active. In the multivariable analysis, risk factors for induced abortion were higher age at the time of the survey (odds ratio [OR] 1.11, 95% CI 1.07– 1.15), lower age at first sexual intercourse (OR 0.87, 95% CI 0.84– 0.91), geographic region (highlands: OR 1.56, 95% CI 1.23– 1.97; jungle: OR 1.81, 95% CI 1.41– 2.31 [v. coastal region]), having children (OR 0.82, 95% CI 0.68– 0.98), having more than 1 sexual partner in lifetime (2 partners: OR 1.61, 95% CI 1.23– 2.09; ≥ 3 partners: OR 2.79, 95% CI 2.12– 3.67), and having 1 or more sexual partners in the year before the survey (1 partner: OR 1.36, 95% CI 1.01– 1.72; ≥ 2 partners: OR 1.54, 95% CI 1.14– 2.02). Overall, 49.0% (95% CI 47.6%– 50.3%) of the women who reported being currently sexually active were not using contraception.

Interpretation

The incidence of clandestine, potentially unsafe induced abortion in Peru is as high as or higher than the rates in many countries where induced abortion is legal and safe. The provision of contraception and safer-sex education to those who require it needs to be greatly improved and could potentially reduce the rate of induced abortion.In most developing countries, induced abortion is legal only if the pregnancy threatens the health or life of the mother. Many women, therefore, seek clandestine abortions, which are too often unsafe and place the woman at risk of complications and death.¹Forty percent of women live in countries where abortion is legally restricted.² In 2003, an estimated 55% of induced abortions in developing countries were unsafe, and 97% of all unsafe abortions were in developing countries.³ Induced abortion is highly restricted in most countries in Latin America and the Caribbean.¹ According to the World Health Organization (WHO), the region of Latin America and the Caribbean has the same estimated incidence of clandestine induced abortions as Africa (3% per year among women aged 15–44 years).⁴ It also has the highest proportion of maternal death from unsafe abortion (12%).⁵ Women who have complications from clandestine abortions may not seek medical help for fear of being reported to legal authorities by health care workers.^6,7Elimination of unsafe abortions is a key component of sexual and reproductive health care.⁸ There is a public health need to determine more accurately the burden of, and risk factors for, clandestine induced abortion in different countries. Because of data limitations, the WHO reports only regional estimates.⁴ The lack of official records and underreporting by those involved make this task difficult, requiring that estimates calculated by different methods be compared.Rates of clandestine induced abortion are estimated with the use of either direct methods, such as population-based surveys and surveys of providers of illegal abortions, or indirect methods, such as the application of multipliers to recorded rates of hospital admission or death attributed to induced abortions.^4,9We performed a large, representative, population-based survey to determine the prevalence and incidence of, and risk factors for, induced abortion in an urban population of a Latin American country where access to abortion services is legally restricted.     

The capsule polysaccharide structure and biogenesis for non-O1 Vibrio cholerae NRT36S: genes are embedded in the LPS region

Background  

In V. cholerae, the biogenesis of capsule polysaccharide is poorly understood. The elucidation of capsule structure and biogenesis is critical to understanding the evolution of surface polysaccharide and the internal relationship between the capsule and LPS in this species. V. cholerae serogroup O31 NRT36S, a human pathogen that produces a heat-stable enterotoxin (NAG-ST), is encapsulated. Here, we report the covalent structure and studies of the biogenesis of the capsule in V. cholerae NRT36S.     

Genomics and the renaissance of generalism

A meeting report of the sessions on human, eukaryotic and bacterial genome sequencing at the American Society for Microbiology and Institut Pasteur joint conference: Genomes 2000 International Conference on Microbial and Model Genomes, Paris, April 11-15, 2000     

Design and baseline characteristics of the ParkFit study,a randomized controlled trial evaluating the effectiveness of a multifaceted behavioral program to increase physical activity in Parkinson patients

Background  

Many patients with Parkinson's disease (PD) lead a sedentary lifestyle. Promotion of physical activities may beneficially affect the clinical presentation of PD, and perhaps even modify the course of PD. However, because of physical and cognitive impairments, patients with PD require specific support to increase their level of physical activity.     

Fairy, tadpole, and clam shrimps (Branchiopoda) in seasonally inundated clay pans in the western Mojave Desert and effect on primary producers

Background

Fairy shrimps (Anostraca), tadpole shrimps (Notostraca), clam shrimps (Spinicaudata), algae (primarily filamentous blue-green algae [cyanobacteria]), and suspended organic particulates are dominant food web components of the seasonally inundated pans and playas of the western Mojave Desert in California. We examined the extent to which these branchiopods controlled algal abundance and species composition in clay pans between Rosamond and Rogers Dry Lakes. We surveyed branchiopods during the wet season to estimate abundances and then conducted a laboratory microcosm experiment, in which dried sediment containing cysts and the overlying algal crust were inundated and cultured. Microcosm trials were run with and without shrimps; each type of trial was run for two lengths of time: 30 and 60 days. We estimated the effect of shrimps on algae by measuring chlorophyll content and the relative abundance of algal species.

Results

We found two species of fairy shrimps (Branchinecta mackini and B. gigas), one tadpole shrimp (Lepidurus lemmoni), and a clam shrimp (Cyzicus setosa) in our wet-season field survey. We collected Branchinecta lindahli in a pilot study, but not subsequently. The dominant taxa were C. setosa and B. mackini, but abundances and species composition varied greatly among playas. The same species found in field surveys also occurred in the microcosm experiment. There were no significant differences as a function of experimental treatments for either chlorophyll content or algal species composition (Microcoleus vaginatus dominated all treatments).

Conclusions

The results suggest that there was no direct effect of shrimps on algae. Although the pans harbored an apparently high abundance of branchiopods, these animals had little role in regulating primary producers in this environment.