STK39 Polymorphism Is Associated with Essential Hypertension: A Systematic Review and Meta-Analysis

Background

A recent genome-wide association study identified STK39as a candidate gene for blood pressure (BP) in Europeans. Subsequently, several studies have attempted to replicate the association across different ethnic populations. However, the results have been inconsistent.

Objective and Methods

We performed a meta-analysis to elucidate the association between the STK39 rs3754777 polymorphism (or proxy) and hypertension. Published literature from PubMed and Embase databases were retrieved and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model.

Results

Using appropriate inclusion/exclusion criteria, we identified 10 studies that included 21, 863 hypertensive cases and 24, 480 controls from different ethnicities. The meta-analysis showed a significant association of STK39 rs3754777 variant with hypertension (OR = 1.10, 95%CI = 1.06–1.15, p = 7.95×10⁻⁶). Further subgroup analysis by ethnicity suggested that the association was significant in Europeans (OR = 1.08, 95% CI = 1.03–1.14, p = 0.002) and in East Asians (OR = 1.16, 95%CI = 1.07–1.25, p = 4.34×10⁻⁴), but not in Africans (OR = 1.01, 95%CI 0.80–1.27, p = 0.932). We further confirmed the positive association by sensitivity analysis. No publication bias was detected (Begg’s test, p = 0.721; Egger’s test, p = 0.744).

Conclusions

The present meta-analysis confirms the significant association of STK39 polymorphism with susceptibility to hypertension in Europeans and East Asians. Future studies should include gene–gene and gene–environment interactions to investigate the identified association.     

Link Clustering Reveals Structural Characteristics and Biological Contexts in Signed Molecular Networks

Many biological networks are signed molecular networks which consist of positive and negative links. To reveal the distinct features between links with different signs, we proposed signed link-clustering coefficients that assess the similarity of inter-action profiles between linked molecules. We found that positive links tended to cluster together, while negative links usually behaved like bridges between positive clusters. Positive links with higher adhesiveness tended to share protein domains, be associated with protein-protein interactions and make intra-connections within protein complexes. Negative links that were more bridge-like tended to make interconnections between protein complexes. Utilizing the proposed measures to group positive links, we observed hierarchical modules that could be well characterized by functional annotations or known protein complexes. Our results imply that the proposed sign-specific measures can help reveal the network structural characteristics and the embedded biological contexts of signed links, as well as the functional organization of signed molecular networks.     

Expression of a Yersinia pseudotuberculosis Type VI Secretion System Is Responsive to Envelope Stresses through the OmpR Transcriptional Activator

The Type VI secretion system (T6SS) is a macromolecular complex widespread in Gram-negative bacteria. Although several T6SS are required for virulence towards host models, most are necessary to eliminate competitor bacteria. Other functions, such as resistance to amoeba predation, biofilm formation or adaptation to environmental conditions have also been reported. This multitude of functions is reflected by the large repertoire of regulatory mechanisms shown to control T6SS expression, production or activation. Here, we demonstrate that one T6SS gene cluster encoded within the Yersinia pseudotuberculosis genome, T6SS-4, is regulated by OmpR, the response regulator of the two-component system EnvZ-OmpR. We first identified OmpR in a transposon mutagenesis screen. OmpR does not control the expression of the four other Y. pseudotuberculosis T6SS gene clusters and of an isolated vgrG gene, and responds to osmotic stresses to bind to and activate the T6SS-4 promoter. Finally, we show that T6SS-4 promotes Y. pseudotuberculosis survival in high osmolarity conditions and resistance to deoxycholate.     

Structural Plasticity in Human Heterochromatin Protein 1β

As essential components of the molecular machine assembling heterochromatin in eukaryotes, HP1 (Heterochromatin Protein 1) proteins are key regulators of genome function. While several high-resolution structures of the two globular regions of HP1, chromo and chromoshadow domains, in their free form or in complex with recognition-motif peptides are available, less is known about the conformational behavior of the full-length protein. Here, we used NMR spectroscopy in combination with small angle X-ray scattering and dynamic light scattering to characterize the dynamic and structural properties of full-length human HP1β (hHP1β) in solution. We show that the hinge region is highly flexible and enables a largely unrestricted spatial search by the two globular domains for their binding partners. In addition, the binding pockets within the chromo and chromoshadow domains experience internal dynamics that can be useful for the versatile recognition of different binding partners. In particular, we provide evidence for the presence of a distinct structural propensity in free hHP1β that prepares a binding-competent interface for the formation of the intermolecular β-sheet with methylated histone H3. The structural plasticity of hHP1β supports its ability to bind and connect a wide variety of binding partners in epigenetic processes.     

Total HIV/AIDS Expenditures in Dehong Prefecture,Yunnan Province in 2010: The First Systematic Evaluation of Both Health and Non-Health Related HIV/AIDS Expenditures in China

Objective

We assessed HIV/AIDS expenditures in Dehong Prefecture, Yunnan Province, one of the highest prevalence regions in China, and describe funding sources and spending for different categories of HIV-related interventions and at-risk populations.

Methods

2010 HIV/AIDS expenditures in Dehong Prefecture were evaluated based on UNAIDS’ National AIDS Spending Assessment methodology.

Results

Nearly 93% of total expenditures for HIV/AIDS was contributed by public sources. Of total expenditures, 52.7% was allocated to treatment and care, 24.5% to program management and administration and 19.8% to prevention. Spending on treatment and care was primarily allocated to the treatment of opportunistic infections. Most (40.4%) prevention spending was concentrated on most-at-risk populations, injection drug users (IDUs), sex workers, and men who have sex with men (MSM), with 5.5% allocated to voluntary counseling and testing. Prevention funding allocated for MSM, partners of people living with HIV and prisoners and other confined populations was low compared to the disproportionate burden of HIV/AIDS in these populations. Overall, people living with HIV accounted for 57.57% of total expenditures, while most-at-risk populations accounted for only 7.99%.

Conclusions

Our study demonstrated the applicability of NASA for tracking and assessing HIV expenditure in the context of China, it proved to be a useful tool in understanding national HIV/AIDS response from financial aspect, and to assess the extent to which HIV expenditure matches epidemic patterns. Limited funding for primary prevention and prevention for MSM, prisoners and partners of people living with HIV, signal that resource allocation to these key areas must be strengthened. Comprehensive analyses of regional and national funding strategies are needed to inform more equitable, effective and cost-effective HIV/AIDS resource allocation.     

Realization of Graphene-Based Tunable Plasmon-Induced Transparency by the Dipole-Dipole Coupling

A numerical and theoretical study is presented on the realization of tunable plasmon-induced transparency (PIT) phenomenon in the three-dimensional patterned graphene nanostrips. The simulation results reveal that the PIT effect is generated due to the excitation of dark mode which can be considered a dipole. The three-level plasmonic system is employed to explain the physical mechanism of the PIT effect. Different from previous reported form (dipole-quadrupole coupling), the proposed is attributed to the dipole-dipole coupling. The PIT effect can be tuned by changing the coupling length between bright and dark mode as well as the Fermi energy of graphene. Our studies provide guidance for fabricating ultra-compact devices in practical application.     

Analysis of Mid-Infrared Surface Plasmon Modes in a Graphene-Based Cylindrical Hybrid Waveguide

A graphene-based cylindrical hybrid surface plasmon polariton waveguide, composed of a silicon nanowire core surrounded by a silica layer and then a graphene layer, is investigated using the finite-difference time-domain method. The analytical solutions and the numerical simulation show that an ultra-small mode area and a large propagation length can be achieved with this waveguide. Utilizing the perturbation theory of coupled mode, we demonstrate that the six lowest-order coupling modes originate from the coupling of the three lowest-order single-waveguide modes, and the m?=?1 order yy-coupling mode possesses the maximum coupling length and the minimum crosstalk. This waveguide can be used for photonic integrated circuits in the mid-infrared range.     

Profile and Determinants of Retinal Optical Intensity in Normal Eyes with Spectral Domain Optical Coherence Tomography

Purpose

To investigate the profile and determinants of retinal optical intensity in normal subjects using 3D spectral domain optical coherence tomography (SD OCT).

Methods

A total of 231 eyes from 231 healthy subjects ranging in age from 18 to 80 years were included and underwent a 3D OCT scan. Forty-four eyes were randomly chosen to be scanned by two operators for reproducibility analysis. Distribution of optical intensity of each layer and regions specified by the Early Treatment of Diabetic Retinopathy Study (ETDRS) were investigated by analyzing the OCT raw data with our automatic graph-based algorithm. Univariate and multivariate analyses were performed between retinal optical intensity and sex, age, height, weight, spherical equivalent (SE), axial length, image quality, disc area and rim/disc area ratio (R/D area ratio).

Results

For optical intensity measurements, the intraclass correlation coefficient of each layer ranged from 0.815 to 0.941, indicating good reproducibility. Optical intensity was lowest in the central area of retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer and photoreceptor layer, except for the retinal pigment epithelium (RPE). Optical intensity was positively correlated with image quality in all retinal layers (0.553<β<0.851, p<0.01), and negatively correlated with age in most retinal layers (-0.362<β<-0.179, p<0.01), except for the RPE (β = 0.456, p<0.01), outer nuclear layer and photoreceptor layer (p>0.05). There was no relationship between retinal optical intensity and sex, height, weight, SE, axial length, disc area and R/D area ratio.

Conclusions

There was a specific pattern of distribution of retinal optical intensity in different regions. The optical intensity was affected by image quality and age. Image quality can be used as a reference for normalization. The effect of age needs to be taken into consideration when using OCT for diagnosis.