404 research outputs found
Analysing the role of GIGANTEA in flowering-time regulation and light signalling of Arabidopsis
Many plants flower in response to environmental cues. Of particular significance in many plants species is initiation of flowering in response to seasonal changes in day length. An internal timing mechanism called the circadian clock enables measurement of daylength (a process called photoperiodism). As daylength changes throughout the year, photoperiodic control of flowering allows plants to develop flowers and reproduce in the appropriate season. Arabidopsis thaliana has become the species of choice in which to study the molecular-genetics of flowering-time control. This species is a facultative long-day plant that flowers much earlier under long days (LD, 16 hours light) than under short days (SD, 8 hours light); however the flowering time is intermediate if the period of light is between these extremes. A severe late flowering phenotype is caused by mutations in the GIGANTEA (GI) gene. This phenotype is at least in part caused by reducing the expression of the flowering-time gene CONSTANS (CO) and thereby delaying the time of flowering under long days. Apart from these effects, the loss-of-function gi mutant also shows shortened circadian rhythms in the expression of circadian controlled genes and lowers the expression of CCA1 and LHY, two genes thought to be closely related to the circadian clock. Additionally, mutations in GI impair the transduction of the red light signal from the photoreceptor phytochrome B. GI is a single copy gene in Arabidopsis and encodes a nuclear protein of 1173 amino acids that is highly conserved in seed plants, but no homologous proteins have been found outside the plant kingdom. The biochemical function of GI is unknown, it is expressed widely throughout the plant and its transcription shows a circadian rhythm with a peak in mRNA abundance 8 till 10 hours after dawn. The timing and duration of this peak is influenced by daylength. I addressed how GI regulates flowering time using three experimental approaches. By exploiting the yeast two hybrid system I screened for proteins interacting with GI from two libraries (total and apex from Arabidopsis). This identified 52 putative interacting proteins of which we selected 15 for further analysis. These 15 proteins were further tested for interaction with the C-terminal domain of GI, which is thought to be involved in flowering. One protein, ATA20, showed a strong interaction and 4 others (CSN6b, a CHD protein-like, a member of the TCP-family and GIP14, a ZZ-finger domain family protein) weaker interactions. Recent results demonstrated that the overexpression of GIP14 caused an elongated hypocotyl phenotype under red-light, suggesting that red-light perception was impaired. This is a similar phenotype to gi mutant plants and suggests that GIP14 might act as a negative regulator of GI protein function. To test the detailed spatial pattern of GI expression, a fusion of the GI promoter to the GUS marker gene was constructed (GI::GUS) and introduced into plants. Staining of whole seedlings, stem and leaves detected GI::GUS expression in young leaves and in the vascular tissue of the root, hypocotyl, cotelydons and leaves. Expression was also detected in the meristem of the root and shoot. This result demonstrated that GI is expressed widely in plants. To test in which tissues GI acts to regulate flowering, region specific promoters were used to misexpress GI in the gi-3 mutant. These experiments showed that expressing GI in the phloem companion cells rescues the late-flowering gi-3 mutant. Additionally, a genetic screen was performed to identify genes related to GI in function. GI increases the expression of LHY and CCA1 and the proteins encoded by these genes repress GI expression. Mutations in GI also suppress the early flowering phenotype of lhy-11 cca1-1 double mutants. An EMS mutagenesis was carried out with the lhy11cca1-1 double mutant and several late-flowering individuals were found under SD. The late flowering slc18 mutation was chosen for further study. Data on flowering-time and expression of GI, CO and FT show its significance in the flowering pathway. slc18 was mapped by using 1700 late flowering F2 plants and located to an interval of 114 kb on the lower arm of chromosome 3. This region contains no genes with a known function in flowering-time control, suggesting that SLC18 encodes a new floral regulator. The corresponding mutation will be finally identified by comparing the DNA sequence of genes in the region between the mutant and wild-type, and by complementation approaches
An optimised algorithm for ionized impurity scattering in Monte Carlo simulations
We present a new optimised model of Brookes-Herring ionized impurity
scattering for use in Monte Carlo simulations of semiconductors. When
implemented, it greatly decreases the execution time needed for simulations
(typically by a factor of the order of 100), and also properly incorporates the
great proportion of small angle scatterings that are neglected in the standard
algorithm. It achieves this performance by using an anisotropic choice of
scattering angle which accurately mimics the true angular distribution of
ionized impurity scattering.Comment: 5 page
China in Africa: a profile of political and economic relations
ASC – Publicaties niet-programma gebonde
China in Afrika: een profiel van politiek-economische relaties
ASC – Publicaties niet-programma gebonde
Brazil-Africa: Booming business across the Atlantic
ASC – Publicaties niet-programma gebonde
Objectives and Methods of Iron Chelation Therapy
Recent developments in the understanding of the molecular control of iron homeostasis provided novel
insights into the mechanisms responsible for normal iron balance. However in chronic anemias associated
with iron overload, such mechanisms are no longer sufficient to offer protection from iron toxicity, and iron
chelating therapy is the only method available for preventing early death caused mainly by myocardial and
hepatic damage. Today, long-term deferoxamine (DFO) therapy is an integral part of the management of
thalassemia and other transfusion-dependent anemias, with a major impact on well-being and survival.
However, the high cost and rigorous requirements of DFO therapy, and the significant toxicity of deferiprone
underline the need for the continued development of new and improved orally effective iron chelators.
Within recent years more than one thousand candidate compounds have been screened in animal models. The
most outstanding of these compounds include deferiprone (L1); pyridoxal isonicotinoyl hydrazone (PIH) and;
bishydroxy- phenyl thiazole. Deferiprone has been used extensively as a substitute for DFO in clinical trials
involving hundreds of patients. However, L1 treatment alone fails to achieve a negative iron balance in a
substantial proportion of subjects. Deferiprone is less effective than DFO and its potential hepatotoxicity is
an issue of current controversy. A new orally effective iron chelator should not necessarily be regarded as
one displacing the presently accepted and highly effective parenteral drug DFO. Rather, it could be employed
to extend the scope of iron chelating strategies in a manner analogous with the combined use of medications
in the management of other conditions such as hypertension or diabetes. Coadministration or alternating use
of DFO and a suitable oral chelator may allow a decrease in dosage of both drugs and improve compliance
by decreasing the demand on tedious parenteral drug administration. Combined use of DFO and L1 has
already been shown to result in successful depletion of iron stores in patients previously failing to respond to single drug therapy, and to lead to improved compliance with treatment. It may also result in a “shuttle effect” between weak intracellular chelators and powerful extracellular chelators or exploit the entero-hepatic cycle to promote fecal iron excretion. All of these innovative ways of chelator usage are now awaiting
evaluation in experimental models and in the clinical setting
A nationwide evaluation of deceased donor kidney transplantation indicates detrimental consequences of early graft loss
Early graft loss (EGL) is a feared outcome of kidney transplantation. Consequently, kidneys with an anticipated risk of EGL are declined for transplantation. In the most favorable scenario, with optimal use of available donor kidneys, the donor pool size is balanced by the risk of EGL, with a tradeoff dictated by the consequences of EGL. To gauge the consequence of EGL we systematically evaluated its impact in an observational study that included all 10,307 deceased-donor kidney transplantations performed in The Netherlands between 1990 and 2018. Incidence of EGL, defined as graft loss within 90 days, in primary transplantation was 8.2% (699/8,511). The main causes were graft rejection (30%), primary nonfunction (25%), and thrombosis or infarction (20%). EGL profoundly impacted short- and long-term patient survival (adjusted hazard ratio; 95% confidence interval: 8.2; 5.1-13.2 and 1.7; 1.3-2.1, respectively). Of the EGL recipients who survived 90 days after transplantation (617/699) only 440 of the 617 were relisted for re-transplantation. Of those relisted, only 298 were ultimately re-transplanted leading to an actual re-transplantation rate of 43%. Noticeably, re-transplantation was associated with a doubled incidence of EGL, but similar long-term graft survival (adjusted hazard ratio 1.1; 0.6-1.8). Thus, EGL after kidney transplantation is a medical catastrophe with high mortality rates, low relisting rates, and increased risk of recurrent EGL following re-transplantation. This implies that detrimental outcomes also involve convergence of risk factors in recipients with EGL. The 8.2% incidence of EGL minimally impacted population mortality, indicating this incidence is acceptable
Systemic arterial calcium burden in patients with chronic limb-threatening ischemia
Introduction: 5-year mortality of chronic limb-threatening ischemia (CLTI) is 50–60% and coronary artery disease (CAD) is the main cause of death of CLTI patients, followed by stroke. The aim of this study is to quantify and qualify the calcium load in different arterial territories in patients with CLTI. Methods: Prospectively, 60 patients with CLTI were included and received a full-body CT scan. 6 patients were excluded. Different arterial territories (the peripheral lower extremity arteries, coronary arteries, extracranial and intracranial carotid arteries, thoracic and abdominal aorta) were analyzed. Analysis and interrelations of both quantitative and semi-quantitative CT measurements was performed. Results: Mean age was 72 years (range 47–95; SD 11.4). Almost all CLTI patients had calcified arterial beds (femoropopliteal 100%, crural 98.1%, coronary 100%, carotid bifurcation 96.2%, internal carotid artery 98.1%, thoracic aorta 96.2%, abdominal aorta 92.3%). Nearly all arterial territories had severe calcifications. 57% had a very high coronary Agatston score (>1000), and 35% extremely high (>2000). Calcifications in the lower extremity were significantly correlated to CAC score, carotid artery bifurcation calcification score, and to a lesser extent correlated to annular calcifications in the aorta. Very high and extremely high total CAC scores were strongly correlated with severe lower extremity arterial calcifications and severe carotid and intracranial internal carotid artery, thoracic and abdominal aorta calcifications in patients with CLTI patients. Conclusions: In CLTI patients nearly all arterial territories are severely calcified, suggesting that systemic calcification plays an important role in the poor outcome of this disease
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