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

Driving pressure during general anesthesia for open abdominal surgery (DESIGNATION) : study protocol of a randomized clinical trial

Background Intraoperative driving pressure (Delta P) is associated with development of postoperative pulmonary complications (PPC). When tidal volume (V-T) is kept constant, Delta P may change according to positive end-expiratory pressure (PEEP)-induced changes in lung aeration. Delta P may decrease if PEEP leads to a recruitment of collapsed lung tissue but will increase if PEEP mainly causes pulmonary overdistension. This study tests the hypothesis that individualized high PEEP, when compared to fixed low PEEP, protects against PPC in patients undergoing open abdominal surgery. Methods The "Driving prESsure durIng GeNeral AnesThesIa for Open abdomiNal surgery trial" (DESIGNATION) is an international, multicenter, two-group, double-blind randomized clinical superiority trial. A total of 1468 patients will be randomly assigned to one of the two intraoperative ventilation strategies. Investigators screen patients aged >= 18 years and with a body mass index <= 40 kg/m(2), scheduled for open abdominal surgery and at risk for PPC. Patients either receive an intraoperative ventilation strategy with individualized high PEEP with recruitment maneuvers (RM) ("individualized high PEEP") or one in which PEEP of 5 cm H2O without RM is used ("low PEEP"). In the "individualized high PEEP" group, PEEP is set at the level at which Delta P is lowest. In both groups of the trial, V-T is kept at 8 mL/kg predicted body weight. The primary endpoint is the occurrence of PPC, recorded as a collapsed composite of adverse pulmonary events. Discussion DESIGNATION will be the first randomized clinical trial that is adequately powered to compare the effects of individualized high PEEP with RM versus fixed low PEEP without RM on the occurrence of PPC after open abdominal surgery. The results of DESIGNATION will support anesthesiologists in their decisions regarding PEEP settings during open abdominal surgery