Latency type-dependent modulation of Epstein-Barr virus-encoded latent membrane protein 1 expression by type I interferons in B cells

We report that type I interferons (IFNs) upregulate latent membrane protein 1 (LMP-1) expression by direct activation of the ED-L1 promoter in several Epstein-Barr virus (EBV)-carrying Burkitt's lymphoma lines. In EBV-infected primary B cells, IFN-α transiently upregulates LMP-1 mRNA, but not protein levels, followed by downregulation of both, suggesting a novel antiproliferative mechanism of type I IFNs. Furthermore, our results may explain the expression of LMP-1 in memory B cells of systemic lupus erythematosus patients.     

Routes to the tonoplast: the sorting of tonoplast transporters in Arabidopsis mesophyll protoplasts

Vacuoles perform a multitude of functions in plant cells, including the storage of amino acids and sugars. Tonoplast-localized transporters catalyze the import and release of these molecules. The mechanisms determining the targeting of these transporters to the tonoplast are largely unknown. Using the paralogous Arabidopsis thaliana inositol transporters INT1 (tonoplast) and INT4 (plasma membrane), we performed domain swapping and mutational analyses and identified a C-terminal di-leucine motif responsible for the sorting of higher plant INT1-type transporters to the tonoplast in Arabidopsis mesophyll protoplasts. We demonstrate that this motif can reroute other proteins, such as INT4, SUCROSE TRANSPORTER2 (SUC2), or SWEET1, to the tonoplast and that the position of the motif relative to the transmembrane helix is critical. Rerouted INT4 is functionally active in the tonoplast and complements the growth phenotype of an int1 mutant. In Arabidopsis plants defective in the β-subunit of the AP-3 adaptor complex, INT1 is correctly localized to the tonoplast, while sorting of the vacuolar sucrose transporter SUC4 is blocked in cis-Golgi stacks. Moreover, we demonstrate that both INT1 and SUC4 trafficking to the tonoplast is sensitive to brefeldin A. Our data show that plants possess at least two different Golgi-dependent targeting mechanisms for newly synthesized transporters to the tonoplast.     

Apolipoprotein A-V is a potential target for treating coronary artery disease: evidence from genetic and metabolomic analyses

Triglyceride (TG)-lowering LPL variants in combination with genetic LDL-C-lowering variants are associated with reduced risk of coronary artery disease (CAD). Genetic variation in the APOA5 gene encoding apolipoprotein A-V also strongly affects TG levels, but the potential clinical impact and underlying mechanisms are yet to be resolved. Here, we aimed to study the effects of APOA5 genetic variation on CAD risk and plasma lipoproteins through factorial genetic association analyses. Using data from 309,780 European-ancestry participants from the UK Biobank, we evaluated the effects of lower TG levels as a result of genetic variation in APOA5 and/or LPL on CAD risk with or without a background of reduced LDL-C. Next, we compared lower TG levels via APOA5 and LPL variation with over 100 lipoprotein measurements in a combined sample from the Netherlands Epidemiology of Obesity study (N = 4,838) and the Oxford Biobank (N = 6,999). We found that lower TG levels due to combined APOA5 and LPL variation and genetically-influenced lower LDL-C levels afforded the largest reduction in CAD risk (odds ratio: 0.78 (0.73–0.82)). Compared to patients with genetically-influenced lower TG via LPL, genetically-influenced lower TG via APOA5 had similar and independent, but notably larger, effects on the lipoprotein profile. Our results suggest that lower TG levels as a result of APOA5 variation have strong beneficial effects on CAD risk and the lipoprotein profile, which suggest apo A-V may be a potential novel therapeutic target for CAD prevention.     

Shedding of the 67-kD laminin receptor by human cancer cells

The 67-kD laminin receptor (67LR) is a cell membrane-associated molecule exhibiting high affinity for the basement membrane glycoprotein, laminin. While export of the 67LR toward the extracellular matrix has been recently suggested by electron microscopy studies, there is to date no evidence of shedding of the 67LR from cells. Using two monoclonal antibodies directed against the 67LR, we developed a double-determinant radioimmunoassay that demonstrates that the 67LR is released from cancer cells into the culture medium. The shed molecule exhibited the same apparent molecular weight as that of the membrane-associated 67LR, suggesting that no proteolytic cleavage is involved in the process. Furthermore, we demonstrate that the 67LR is not anchored to the membrane through a glycolsyl-phosphatidylinositol bridge. However, the observation that lactose increased the release of 67LR suggests that a lectin-type interaction is involved in the cell membrane association of this laminin binding protein and the cell surface. Interestingly, the released 67LR recovered after HPLC gel filtration was found free as well as associated to high molecular weight complexes. The free 67LR retained its ability to bind to the cell surface. Our study is the first demonstration that the 67LR is effectively shed by cancer cells. The released free 67LR could play an important role in modulating interactions between cancer cells and laminin during tumor invasion and metastasis. © 1996 Wiley-Liss, Inc.     

Positive effects of plantar vibration training for the treatment of diabetic peripheral neuropathy: A pilot study

Purpose: To evaluate the effectiveness of 8-week low-frequency plantar vibration training on patients with sensorimotor diabetic peripheral neuropathy (DPN).

Participants: Twelve patients took part in the investigation.

Results: An increase of the nerve conductive velocity of soral and peroneal nerves of feet, increased postural stability, and disappearance of the pain and tingling were observed.

Conclusion: The obtained results provide evidence for beneficial effects of 8-week plantar vibration training in patients with DPN.     

Tolerance of β-diketone hydrolases as representatives of the crotonase superfamily towards organic solvents

Crotonase superfamily enzymes catalyze a wide variety of reactions, including hydrolytic C–C bond cleavage in symmetrical β‐diketones by 6‐oxo camphor hydrolase (OCH) from Rhodococcus sp. The organic solvent tolerance and temperature stability of OCH and its structurally related ortholog Anabaena β‐diketone hydrolase have been investigated. Both enzymes showed excellent tolerance toward organic solvents; for instance, even in the presence of 80% (v/v) THF or dioxane, OCH was still active. In most solvent mixtures, except methanol, the stereospecificity was conserved (>99% e.e. of product), hence neither the type of solvent nor its concentration appeared to have an effect on the stereoselectivity of the enzyme. Attempts to correlate the observed activities with log P, functional solvent group or denaturing capacity (DC) of the solvent were only successful in the case of DC for water miscible solvents. This study represents the first investigation of organic solvent stability for members of the crotonase superfamily. Biotechnol. Bioeng. 2011;108: 2815–2822. © 2011 Wiley Periodicals, Inc.     

Direct versus indirect radiation action in irradiated vegetal embryos

Maize is one of model plants useful for genetic investigations and also very important for its agrotechnical utilizations. Here the genotoxic effects of low dose X-rays and accelerated electrons in maize caryopses was carried out with focus on the influence of water content at the moment of seed irradiation. X-ray photon beam as well as accelerated electrons were provided with 2.40 Gy min^?1 dose rate. Pre-soaked and dry maize caryopses were irradiated with 0.5–3.0–6.0 Gy. Cytogenetic investigations were carried out based on microscope observations of chromosomes stained by Feulgen method. The mitotic index was found diminished in hydrated samples indicating the negative influence of indirect effects of water radicals. As known the water radiolysis release free radicals that attack biomolecules in addition to the directly absorbed radiation impact. Slight positive influence of 0.5 Gy radiation dose on cell division was evidenced. Chromosomal aberrations were identified like: vagrand chromosomes, C-metaphases, picnotic chromosomes, chromatide bridges. General tendency of aberrant mitoses enhancing was recorded in watered samples — with up to the twice increase for 6.0 Gy radiation dose. The results evidenced the hydration role in monitoring cytogenetic effects of low dose radiations in plant systems -with possible biotechnological applications.     

“Give,but Give until It Hurts”: The Modulatory Role of Trait Emotional Intelligence on the Motivation to Help

Two studies investigated the effect of trait Emotional Intelligence (trait EI) on people’s motivation to help. In Study 1, we developed a new computer-based paradigm that tested participants’ motivation to help by measuring their performance on a task in which they could gain a hypothetical amount of money to help children in need. Crucially, we manipulated participants’ perceived efficacy by informing them that they had been either able to save the children (positive feedback) or unable to save the children (negative feedback). We measured trait EI using the Trait Emotional Intelligence Questionnaire–Short Form (TEIQue-SF) and assessed participants’ affective reactions during the experiment using the PANAS-X. Results showed that high and low trait EI participants performed differently after the presentation of feedback on their ineffectiveness in helping others in need. Both groups showed increasing negative affective states during the experiment when the feedback was negative; however, high trait EI participants better managed their affective reactions, modulating the impact of their emotions on performance and maintaining a high level of motivation to help. In Study 2, we used a similar computerized task and tested a control situation to explore the effect of trait EI on participants’ behavior when facing failure or success in a scenario unrelated to helping others in need. No effect of feedback emerged on participants’ emotional states in the second study. Taken together our results show that trait EI influences the impact of success and failure on behavior only in affect-rich situation like those in which people are asked to help others in need.     

Dihydrotestosterone potentiates insulin to up-regulate prokineticin-1 in decidualizing human endometrial stromal cells

Prokineticin 1 (PROK1) is a key regulator of embryo implantation and placentation, and its dysregulation is associated with pregnancy complications, such as pre-eclampsia and foetal growth restriction. We have previously shown that insulin strongly enhances the expression of PROK1 in human decidualizing stromal cells. Here, we demonstrate that dihydrotestosterone (DHT), but not testosterone, potentiates insulin to up-regulate PROK1 in these cells. However, the androgens alone do not influence the expression of PROK1. Our findings suggest that insulin and androgens both are involved in the regulation of PROK1 that could have implications for normal and pathological pregnancies.