Description: Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Although IBDV-induced immunosuppression has been well established, the underlying exact molecular mechanism for such induction is not very clear. We report here the identification of IBDV VP4 as an interferon suppressor by interaction with the glucocorticoid-induced leucine zipper (GILZ) in host cells. We found that VP4 suppressed the expression of type I interferon in HEK293T cells after tumor necrosis factor alpha (TNF-α) treatment or Sendai virus (SeV) infection and in DF-1 cells after poly(I·C) stimulation. In addition, the VP4-induced suppression of type I interferon could be completely abolished by knockdown of GILZ by small interfering RNA (siRNA). Furthermore, knockdown of GILZ significantly inhibited IBDV growth in host cells, and this inhibition could be markedly mitigated by anti-alpha/beta interferon antibodies in the cell cultures ( P 〈 0.001). Thus, VP4-induced suppression of type I interferon is mediated by interaction with GILZ, a protein that appears to inhibit cell responses to viral infection.

Description: Polyelectrolyte-enhanced ultrafiltration was investigated for rhenium(VII) recovery from aqueous solutions by using polyquaternium-6 (PQ6) as a complexing agent. The effects of the operating parameters on the permeate flux ( J ) and the rhenium rejection coefficient ( R ) were studied. In the process of concentration, J declines slowly and R is about 1. The concentrated solution was used for the decomplexation. It takes 10 min to achieve the decomplexation equilibrium at a chloride ion concentration of 100 mg L –1 . The decomplexation percentage reaches 45.6 %. In the diafiltration process, rhenium is extracted effectively, and the purification of the regenerated PQ6 is satisfactory. The regenerated PQ6 was used to bind rhenium(VII). The binding capacity of the regenerated PQ6 is close to that of fresh PQ6. Polyelectrolyte-enhanced ultrafiltration was originally used to achieve the recovery of rhenium from aqueous solutions with the help of polyquaternium-6. The effects of various operating parameters on the permeate flux and the rhenium rejection coefficient were investigated. The integration of four experiments including concentration, decomplexation, diafiltration and reuse of the regenerated polymer was carried out.

Description: Objective— Mechanisms underlying the cardiovascular risk of lipoprotein(a) are poorly understood. We investigated the relationship of apolipoprotein(a) (apo(a)) size, lipoprotein(a), and allele-specific apo(a) levels with HIV disease activity parameters in a biethnic population. Methods and Results— Lipoprotein(a) and allele-specific apo(a) levels were determined in 139 white and 168 black HIV-positive patients. Plasma HIV RNA viral load and CD4+ T-cell count were used as surrogates for disease activity. Lipoprotein(a) and allele-specific apo(a) levels were higher in blacks than whites (for both P 〈0.001). Apo(a) allele size distribution was similar between the 2 ethnic groups, with a median apo(a) size of 28 kringle 4 repeats. Allele-specific apo(a) levels were positively associated with CD4+ T-cell count ( P =0.027) and negatively with plasma HIV RNA viral load ( P 〈0.001). Further, allele-specific apo(a) levels associated with smaller (〈28 kringle 4) atherogenic apo(a) sizes were higher in subjects with CD4+ T-cell counts of ≥350 ( P =0.002). Conclusion— Allele-specific apo(a) levels were higher in subjects with high CD4+ T-cell count or low plasma HIV RNA viral load. The findings suggest that HIV disease activity reduced allele-specific apo(a) levels. Higher allele-specific apo(a) levels associated with atherogenic small apo(a) sizes might contribute to increased cardiovascular risk in HIV-positive subjects with improved disease status.

Description: Aims The aim of this study was to investigate the predictive ability of paced QRS duration (pQRSd) for heart failure events among patients receiving right ventricular apical pacing (RVAP). Methods and results A total of 194 patients with complete atrioventricular block receiving pacemaker treatment were enrolled and stratified to group 1, pQRSd 〈 160 ms, n = 53; group 2, 160 ≤ pQRSd 〈 190 ms, n = 97; and group 3, pQRSd ≥ 190 ms, n = 44. Study outcomes were heart failure events, changes in pQRSd, and changes in left ventricular ejection fraction (LVEF). During the 3-year follow-up, the incidence of heart failure events was 9.4, 27.8, and 56.8% in groups 1, 2, and 3, respectively ( P 〈 0.001). Among the patients without heart failure events, the pQRSd at 3 years remained longer than that at baseline (162.1 ± 22.6 vs. 160.9 ± 22.1 ms, P 〈 0.05), whereas among patients who experienced heart failure events, the prolonged pQRSd at 3 years seemed more pronounced as compared with baseline (184.1 ± 21.1 vs. 179.8 ± 21 ms, P 〈 0.001). Linear regression demonstrated that a decrease in LVEF was positively correlated with pQRSd over time (relative risk 0.423; P 〈 0.05). The receiver operating charactersitic curve showed that the cut-off value of pQRSd was 165 ms with a sensitivity of 0.789. Conclusion A prolonged pQRSd has a detrimental effect on long-term cardiac function during RVAP in patients with complete atrioventricular block. pQRSd could be a useful predictor to identify patients who are at risk for heart failure events during RVAP.

Description: Mycobacterium tuberculosis disease represents an enormous global health problem, with exceptionally high morbidity and mortality in HIV-seropositive (HIV + ) persons. Alveolar macrophages from HIV + persons demonstrate specific and targeted impairment of critical host cell responses, including impaired M. tuberculosis -mediated tumor necrosis factor (TNF) release and macrophage apoptosis. Vitamin D may promote anti- M. tuberculosis responses through upregulation of macrophage NO, NADPH oxidase, cathelicidin, and autophagy mechanisms, but whether vitamin D promotes anti- M. tuberculosis mechanisms in HIV + macrophages is not known. In the current study, human macrophages exposed to M. tuberculosis demonstrated robust release of TNF, IB degradation, and NF-B nuclear translocation, and these responses were independent of vitamin D pretreatment. In marked contrast, HIV + U1 human macrophages exposed to M. tuberculosis demonstrated very low TNF release and no significant IB degradation or NF-B nuclear translocation, whereas vitamin D pretreatment restored these critical responses. The vitamin D-mediated restored responses were dependent in part on macrophage CD14 expression. Importantly, similar response patterns were observed with clinically relevant human alveolar macrophages from healthy individuals and asymptomatic HIV + persons at high clinical risk of M. tuberculosis infection. Taken together with the observation that local bronchoalveolar lavage fluid (BALF) levels of vitamin D are severely deficient in HIV + persons, the data from this study demonstrate that exogenous vitamin D can selectively rescue impaired critical innate immune responses in vitro in alveolar macrophages from HIV + persons at risk for M. tuberculosis disease, supporting a potential role for exogenous vitamin D as a therapeutic adjuvant in M. tuberculosis infection in HIV + persons.

Description: Background and Purpose— To determine the effect of a multifaceted stroke telerehabilitation (STeleR) intervention on physical function, and secondarily on disability, in veterans poststroke. Methods— We conducted a prospective, randomized, multisite, single-blinded trial in 52 veterans with stroke from 3 Veterans Affairs medical centers. Veterans with a stroke in the preceding 24 months were randomized to the STeleR intervention or usual care. The STeleR intervention consisted of 3 home visits, 5 telephone calls, and an in-home messaging device provided over 3 months to instruct patients in functionally based exercises and adaptive strategies. Usual care participants received routine rehabilitation care as prescribed by their physicians. The primary outcome measures were improvement in function at 6 months, measured by both the motor subscale of the Telephone Version of Functional Independence Measure and by the function scales of the Late-Life Function and Disability Instrument. Results— The 2 complementary primary outcomes (Late-Life Function and Disability Instrument Function and Telephone Version of Functional Independence Measure) improved at 6 months for the STeleR group and declined for the usual care group, but the differences were not statistically significant ( P =0.25, Late-Life Function and Disability Instrument; P =0.316). Several of secondary outcomes were statistically significant. At 6 months, compared with the usual care group, the STeleR group showed statistically significant improvements in 4 of the 5 Late-Life Function and Disability Instrument disability component subscales ( P 〈0.05), and approached significance in 1 of the 3 Function component subscales ( P =0.06). Conclusions— The STeleR intervention significantly improved physical function, with improvements persisting up to 3 months after completing the intervention. STeleR could be a useful supplement to traditional poststroke rehabilitation given the limited resources available for in-home rehabilitation for stroke survivors. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00384748.

Description: Objective— Adventitia acts as an active participant in vascular inflammation but the precise mechanism underlying adventitia–mediated vascular inflammation is not fully understood. In this study, we sought to determine whether vascular endothelial growth factor (VEGF) regulates osteopontin (OPN) expression through Flt-1 in adventitial fibroblasts (AFs) to mediate vascular inflammation and neointima formation. Methods and Results— In primary cultured AFs, VEGF increased intracellular and secreted OPN expression in a time- and dose-dependent manner, which was effectively suppressed by a specific anti-Flt-1 hexapeptide. Interestingly, VEGF treatment of AFs enhanced the capability of AF-conditioned medium to stimulate macrophages chemotaxis, and this effect was attenuated after blockade of OPN from AF-conditioned medium. Furthermore, perivascular delivery of anti-Flt-1 peptide preferentially concentrated in the adventitia resulted in a decrease of neointima formation after balloon injury in carotid arteries. The inhibition of neointima formation was preceded by significant reduction of VEGF and OPN expression with concurrent macrophage infiltration into adventitia after injury. Activation of extracellular signal–regulated kinase 1/2 pathway was involved in OPN upregulation and macrophage chemotaxis. Conclusion— These results demonstrate that VEGF/Flt-1 signaling plays a significant role in vascular inflammation and neointima formation by regulating OPN expression in AFs and provide insight into Flt-1 as a potential therapeutic target for vascular diseases.

Description: Objective— To evaluate the associations between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis. Methods and Results— A total of 8632 participants aged ≥40 years from Jiading district, Shanghai, were included in the present study. The presence of NAFLD was evaluated by ultrasonography. Carotid intima-media thickness (CIMT) and brachial-ankle pulse wave velocity (ba-PWV) were measured in each participant. The prevalence of NAFLD was 30.0% in the total population, with 30.3% in men and 29.9% in women, respectively. Subjects with NAFLD had remarkably higher CIMT and ba-PWV compared with those without NAFLD (0.594±0.105 mm versus 0.578±0.109 mm, P 〈0.0001; 1665±424 cm/s versus 1558±430 cm/s, P 〈0.0001). Subjects with both NAFLD and metabolic syndrome had significantly higher CIMT and ba-PWV compared with those with neither or either of these 2 diseases after adjustment for age and sex (all P 〈0.05). Logistic regressions also revealed that NAFLD conferred 35% and 30% increased odds ratios of elevated CIMT and ba-PWV, independent of conventional risk factors and the presence of metabolic syndrome. Conclusion— NAFLD was associated with elevated CIMT and ba-PWV, independent of conventional cardiovascular disease risk factors and metabolic syndrome. The effects of NAFLD and metabolic syndrome on atherosclerosis might not fully overlap.

Description: Well-characterized promoters are essential tools for metabolic engineering and synthetic biology. In Streptomyces coelicolor , the native kasO p is a temporally expressed promoter strictly controlled by two regulators, ScbR and ScbR2. In this work, first, kasO p was engineered to remove a common binding site of ScbR and ScbR2 upstream of its core region, thus generating a stronger promoter, kasO p 3 . Second, another ScbR binding site internal to the kasO p 3 core promoter region was abolished by random mutation and screening of the mutant library to obtain the strongest promoter, kasO p* (where the asterisk is used to distinguish the engineered promoter from the native promoter). The activities of kasO p* were compared with those of two known strong promoters, ermE p* and SF14p, in three Streptomyces species. kasO p* showed the highest activity at the transcription and protein levels in all three hosts. Furthermore, relative to ermE p* and SF14p, kasO p* was shown to confer the highest actinorhodin production level when used to drive the expression of actII -ORF4 in S. coelicolor . Therefore, kasO p* is a simple and well-defined strong promoter useful for gene overexpression in streptomycetes.

Description: [1]  In this paper, the essential technique of Grad-Shafranov (GS) reconstruction is reformulated into an inverse boundary value problems (IBVPs) for Laplace's equation on a circle by introducing a Hilbert transform between the normal and tangent component of the boundary gradients. It is proved that the specified IBVPs have unique solution, given the known Dirichlet and Neumann conditions on certain arc. Even when the arc is reduced to only one point on the circle, it can be inferred logically that the unique solution still exists there on the remaining circle. New solution approach for the specified IBVP is suggested with the help of the introduced Hilbert transform. An iterated Tikhonov regularization scheme is applied to deal with the ill-posed linear operators appearing in the discretization of the new approach. Numerical experiments highlight the efficiency and robustness of the proposed method. According to linearity of the elliptic operator in GS equation, its solution can be divided into twoparts. One is solved from a semi-linear elliptic equation with an homogeneous Dirichlet boundary condition. The other is solved from the IBVP of Laplace's equation. It is concluded that there exists a unique solution for the so-called elliptic Cauchy problem for the essential technique of GS-reconstruction.