Serial interferon-gamma release assays during treatment of active tuberculosis in young adults

<p>Abstract</p> <p>Background</p> <p>The role of interferon-γ release assay (IGRA) in monitoring responses to anti-tuberculosis (TB) treatment is not clear. We evaluated the results of the QuantiFERON-TB Gold In-tube (QFT-GIT) assay over time during the anti-TB treatment of adults with no underlying disease.</p> <p>Methods</p> <p>We enrolled soldiers who were newly diagnosed with active TB and admitted to the central referral military hospital in South Korea between May 1, 2008 and September 30, 2009. For each participant, we preformed QFT-GIT assay before treatment (baseline) and at 1, 3, and 6 months after initiating anti-TB medication.</p> <p>Results</p> <p>Of 67 eligible patients, 59 (88.1%) completed the study protocol. All participants were males who were human immunodeficiency virus (HIV)-negative and had no chronic diseases. Their median age was 21 years (range, 20-48). Initially, 57 (96.6%) patients had positive QFT-GIT results, and 53 (89.8%), 42 (71.2%), and 39 (66.1%) had positive QFT-GIT results at 1, 3, and 6 months, respectively. The IFN-γ level at baseline was 5.31 ± 5.34 IU/ml, and the levels at 1, 3, and 6 months were 3.95 ± 4.30, 1.82 ± 2.14, and 1.50 ± 2.12 IU/ml, respectively. All patients had clinical and radiologic improvements after treatment and were cured. A lower IFN-γ level, C-reactive protein ≥ 3 mg/dl, and the presence of fever (≥ 38.3°C) at diagnosis were associated with negative reversion of the QFT-GIT assay.</p> <p>Conclusion</p> <p>Although the IFN-γ level measured by QFT-GIT assay decreased after successful anti-TB treatment in most participants, less than half of them exhibited QFT-GIT reversion. Thus, the reversion to negativity of the QFT-GIT assay may not be a good surrogate for treatment response in otherwise healthy young patients with TB.</p

O-GlcNAc modification of leucyl-tRNA synthetase 1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine

All living organisms have the ability to sense nutrient levels to coordinate cellular metabolism. Despite the importance of nutrient-sensing pathways that detect the levels of amino acids and glucose, how the availability of these two types of nutrients is integrated is unclear. Here, we show that glucose availability regulates the central nutrient effector mTORC1 through intracellular leucine sensor leucyl-tRNA synthetase 1 (LARS1). Glucose starvation results in O-GlcNAcylation of LARS1 on residue S1042. This modification inhibits the interaction of LARS1 with RagD GTPase and reduces the affinity of LARS1 for leucine by promoting phosphorylation of its leucine-binding site by the autophagy-activating kinase ULK1, decreasing mTORC1 activity. The lack of LARS1 O-GlcNAcylation constitutively activates mTORC1, supporting its ability to sense leucine, and deregulates protein synthesis and leucine catabolism under glucose starvation. This work demonstrates that LARS1 integrates leucine and glucose availability to regulate mTORC1 and the metabolic fate of leucine. Leucyl-tRNA synthetase 1 (LARS1) is a leucine sensor for mTORC1 signaling and regulates leucine utilization depending on glucose availability. Here, the author show that O-GlcNAcylation of LARS1 is crucial for its ability to regulate mTORC1 activity and leucine metabolism upon glucose starvation

The contribution of insects to global forest deadwood decomposition

The amount of carbon stored in deadwood is equivalent to about 8 per cent of the global forest carbon stocks. The decomposition of deadwood is largely governed by climate with decomposer groups—such as microorganisms and insects—contributing to variations in the decomposition rates. At the global scale, the contribution of insects to the decomposition of deadwood and carbon release remains poorly understood. Here we present a field experiment of wood decomposition across 55 forest sites and 6 continents. We find that the deadwood decomposition rates increase with temperature, and the strongest temperature effect is found at high precipitation levels. Precipitation affects the decomposition rates negatively at low temperatures and positively at high temperatures. As a net effect—including the direct consumption by insects and indirect effects through interactions with microorganisms—insects accelerate the decomposition in tropical forests (3.9% median mass loss per year). In temperate and boreal forests, we find weak positive and negative effects with a median mass loss of 0.9 per cent and −0.1 per cent per year, respectively. Furthermore, we apply the experimentally derived decomposition function to a global map of deadwood carbon synthesized from empirical and remote-sensing data, obtaining an estimate of 10.9 ± 3.2 petagram of carbon per year released from deadwood globally, with 93 per cent originating from tropical forests. Globally, the net effect of insects may account for 29 per cent of the carbon flux from deadwood, which suggests a functional importance of insects in the decomposition of deadwood and the carbon cycle

Inhibition of epidermal growth factor-induced cell transformation and activator protein 1 activation by [6]-gingerol

Many spices, including plants of the ginger family, possess anticarcinogenic activity. However, the molecular mechanisms by which they exert their antitumorigenic effects are unknown. Activator protein 1 (AP-1) has a critical role in tumor promotion, and blocking of tumor promoter-induced activation of AP-1 inhibits neoplastic transformation. Epidermal growth factor induces cell transformation and AP-1 activity. The purpose of this study was to investigate the effect of two structurally related compounds of the ginger family, [6]-gingerol and [6]-paradol, on EGF-induced cell transformation and AP-1 activation. Our results provide the first evidence that both block EGF-induced cell transformation but act by different mechanisms

Solution-Shear-Processed Quaterrylene Diimide Thin-Film Transistors Prepared by Pressure-Assisted Thermal Cleavage of Swallow Tails

A scalable synthesis of swallow-tailed quaterrylene diimides (STQDIs) and a method for the solution processing of sparingly soluble quaterrylene diimide (QDI) thin films are described. The pressure-assisted thermal cleavage of swallow tails yields crystalline QDI layers with electron mobility up to 0.088 cm(2) V(-1) s(-1). The developed method opens up a new route toward the solution processing of higher rylene diimides with poor solubility.close302

Numerical investigation of the effects of prosthetic aortic valve design on aortic hemodynamic characteristics

The superior performance of single-point attached commissures (SPAC) molded valve design has been validated by several numerical, in vitro and in vivo animal studies. However, the impacts of the SPAC molded valve design on aortic hemodynamic environments are yet to be investigated. In this study, multiscale computational models were prepared by virtually implanting prosthetic aortic valves with SPAC tubular, SPAC molded and conventional designs into a patient-specific aorta, respectively. The impacts of the valve designs on efferent flow distribution, flow pattern and hemodynamic characteristics in the aorta were numerically investigated. The results showed that despite the overall flow phenomena being similar, the SPAC tubular valve exhibited a suboptimal performance in terms of higher spatially averaged wall shear stress (SAWSS) in ascending aorta (AAo), higher helix grade, stronger secondary flow mean secondary velocity in descending aorta, as well as more complex vortex distribution. The results from the current study extend the understanding of hemodynamic impacts of the valve designs, which would further benefit the optimization of the prosthetic aortic valve.Published versio

Synthesis of ultra-thin tellurium nanoflakes on textiles for high-performance flexible and wearable nanogenerators

We report that ultra-thin tellurium (Te) nanoflakes were successfully grown on a sample of a gold-coated textile, which then was used as an active piezoelectric material. An output voltage of 4 V and a current of 300 nA were obtained from the bending test under a driving frequency of 10 Hz. To test the practical applications, Te nanoflake nanogenerator (TFNG) device was attached to the subject&apos;s arm, and mechanical energy was converted to electrical energy by means of periodic arm-bending motions. The optimized open-circuit voltage and short-circuit current density of approximately 125 V and 17 μA/cm2, respectively, were observed when a TFNG device underwent a compression test with a compressive force of 8 N and driving frequency of 10 Hz. This high-power generation enabled the instantaneous powering of 10 green light-emitting diodes that shone without any assistance from an external power source. © 2016 Elsevier B.V.1