7,346 research outputs found

    Probing the nucleotide-binding activity of a redox sensor: two-component regulatory control in chloroplasts

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    Two-component signal transduction systems mediate adaptation to environmental changes in bacteria, plants, fungi, and protists. Each two-component system consists of a sensor histidine kinase and a response regu- lator. Chloroplast sensor kinase (CSK) is a modified sensor histidine kinase found in chloroplasts—photosynthetic organelles of plants and algae. CSK regulates the tran- scription of chloroplast genes in response to changes in photosynthetic electron transport. In this study, the full- length and truncated forms of Arabidopsis CSK proteins were overexpressed and purified in order to characterise their kinase and redox sensing activities. Our results show that CSK contains a modified kinase catalytic domain that binds ATP with high affinity and forms a quinone adduct that may confer redox sensing activity

    Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target

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    Secondary visual loss occurs in millions of patients due to a wound-healing response, known as posterior capsule opacification (PCO), following cataract surgery. An intraocular lens (IOL) is implanted into residual lens tissue, known as the capsular bag, following cataract removal. Standard IOLs allow the anterior and posterior capsules to become physically connected. This places pressure on the IOL and improves contact with the underlying posterior capsule. New open bag IOL designs separate the anterior capsule and posterior capsules and further reduce PCO incidence. It is hypothesised that this results from reduced cytokine availability due to greater irrigation of the bag. We therefore explored the role of growth factor restriction on PCO using human lens cell and tissue culture models. We demonstrate that cytokine dilution, by increasing medium volume, significantly reduced cell coverage in both closed and open capsular bag models. This coincided with reduced cell density and myofibroblast formation. A screen of 27 cytokines identified nine candidates whose expression profile correlated with growth. In particular, VEGF was found to regulate cell survival, growth and myofibroblast formation. VEGF provides a therapeutic target to further manage PCO development and will yield best results when used in conjunction with open bag IOL designs

    Distinct effects of folate pathway genes MTHFR and MTHFD1L on ruminative response style: a potential risk mechanism for depression

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    Alterations in the folate pathway have been related to both major depression and cognitive inflexibility; however, they have not been investigated in the genetic background of ruminative response style, which is a form of perseverative cognition and a risk factor for depression. In the present study, we explored the association of rumination (measured by the Ruminative Responses Scale) with polymorphisms of two distinct folate pathway genes, MTHFR rs1801133 (C677T) and MTHFD1L rs11754661, in a combined European white sample from Budapest, Hungary (n=895) and Manchester, United Kingdom (n=1309). Post hoc analysis investigated whether the association could be replicated in each of the two samples, and the relationship between folate pathway genes, rumination, lifetime depression and Brief Symptom Inventory depression score. Despite its functional effect on folate metabolism, the MTHFR rs1801133 showed no effect on rumination. However, the A allele of MTHFD1L rs11754661 was significantly associated with greater rumination, and this effect was replicated in both the Budapest and Manchester samples. In addition, rumination completely mediated the effects of MTHFD1L rs11754661 on depression phenotypes. These findings suggest that the MTHFD1L gene, and thus the C1-THF synthase enzyme of the folate pathway localized in mitochondria, has an important effect on the pathophysiology of depression through rumination, and maybe via this cognitive intermediate phenotype on other mental and physical disorders. Further research should unravel whether the reversible metabolic effect of MTHFD1L is responsible for increased rumination or other long-term effects on brain development

    Enhancement of affective processing induced by bifrontal transcranial direct current stimulation in patients with major depression

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    ObjectiveOur aim was to evaluate whether one single section of transcranial direct current stimulation (tDCS), a neuromodulatory technique that noninvasively modifies cortical excitability, could induce acute changes in the negative attentional bias in patients with major depression. Subjects and MethodsRandomized, double-blind, sham-controlled, parallel design enrolling 24 age-, gender-matched, drug-free, depressed subjects. Anode and cathode were placed over the left and right dorsolateral prefrontal cortex. We performed a word Emotional Stroop Task collecting the response times (RTs) for positive-, negative-, and neutral-related words. The emotional Stroop effect for negative vs. neutral and vs. positive words was used as the measure of attentional bias. ResultsAt baseline, RTs were significantly slower for negative vs. positive words. We found that active but not sham tDCS significantly modified the negative attentional bias, abolishing slower RT for negative words. ConclusionActive but not sham tDCS significantly modified the negative attentional bias. These findings add evidence that a single tDCS session transiently induces potent changes in affective processing, which might be one of the mechanisms of tDCS underlying mood changes

    Progress in development of graded bandgap thin film solar cells with electroplated materials

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    Photovoltaic devices are developed mainly based on p-n or p-i-n type device structures, and these devices can utilise only a fraction of the solar spectrum. In order to further improve device parameters and move towards low-cost and high-efficiency next generation solar cells, device architectures capable of harvesting all photons available should be designed and developed. One such architecture is the fully graded bandgap device structure as proposed recently based on both n-type and p-type window layers. These designs have been experimentally tested using well researched GaAs/AlGaAs system producing impressive device parameters of open circuit voltage (Voc) ~1175 mV and fill factor (FF) ~0.85. The devices have also been experimentally tested for the evidence of impurity photovoltaic (PV) effect and impact ionisation taking place within the same device. Since these structures have been experimentally proved with a well-established semiconductor, the effort has been focussed on developing these devices using low-cost and scalable electroplated semiconductors, in order to minimise manufacturing cost. This paper reviews and summarises the work carried out during the past decade on this subject. Graded bandgap devices produced using only two or three electroplated semiconductor layers have been explored and their conversion efficiencies have gradually increased from 10.0%, through 12.8% to 15.3% for different structures. While the work is progressing along this line, the paper summarises the achievements to date

    Field Response of Magnetic Vortices in Dusty Olivine From the Semarkona Chondrite

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    Recent paleomagnetic studies have constrained the strength and longevity of the magnetic field generated by the solar nebula, which has broad implications for the early evolution of the solar system. Paleomagnetic evidence was recorded by nanoscale iron inclusions in olivine crystals in the Semarkona LL 3.0 chondrite. These dusty olivines, have been shown to be credible carriers of ancient magnetic remanence. The small scale of the iron inclusions presents several challenges for defining their fundamental magnetic properties. Here we present the first correlative study of the response of these magnetic structures under applied laboratory fields. Results show that the majority of particles are in a single‐vortex state and exhibit stable magnetic behavior in applied fields up to 200 mT. Experimental observations using Lorentz microscopy and magnetic transmission X‐ray microscopy are shown to compare well with the results of finite‐element micromagnetic simulations derived from 3D models of the particles obtained using electron tomography. This correlative approach may be used to characterize the fundamental magnetic behavior of many terrestrial and extraterrestrial paleomagnetic carriers in the single‐ to multi‐vortex size range, which represent the vast majority of stable magnetic carriers in rocks and meteorites.ERC Grant Agreement No. 32075

    Oligomeric states in sodium ion-dependent regulation of cyanobacterial histidine kinase-2

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    IMI thanks Queen Mary University of London for a graduate teaching studentship. LW thanks the China Scholarship Council (CSC) and Queen Mary University of London for financial support. SP held a Leverhulme Trust early-career post-doctoral research fellowship. JN is grateful for the continued support of the JST CREST Grant Number JPMJCR13M4, Japan. JFA acknowledges the support of research grant F/07 476/AQ and fellowship EM-2015-068 of the Leverhulme Trust
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