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Gibberellins (GAs) are phytohormones that regulate growth and development. DELLA proteins repress GA responses. GA binding to its receptor triggers a series of events that culminate in the destruction of DELLA proteins by the 26S proteasome, which removes the repression of GA signalling. DELLA proteins are transcription co-activators that induce the expression of genes which encode products that inhibit GA responses. In addition to repressing GA responses, DELLA proteins influence the activity of other signalling pathways and serve as a central hub from which other pathways influence GA signalling. In this role, DELLA proteins bind to and inhibit proteins, including transcription factors that act in the signalling pathways of other hormones and light. The binding of these proteins to DELLA proteins also inhibits DELLA activity. GA signalling is subject to homoeostatic regulation through GA-induced repression of GA biosynthesis gene expression, and increased production of the GA receptor and enzymes that catabolize bioactive GAs. This review also discusses the nature of mutant DELLA alleles that are used to produce high-yielding 'Green Revolution' cereal varieties, and highlights important gaps in our knowledge of GA signalling.The phytohormone abscisic acid (ABA) plays crucial roles in numerous physiological processes during plant growth and abiotic stress responses. The endogenous ABA level is controlled by complex regulatory mechanisms involving biosynthesis, catabolism, transport and signal transduction pathways. This complex regulatory network may target multiple levels, including transcription, translation and post-translational regulation of genes involved in ABA responses. Most of the genes involved in ABA biosynthesis, catabolism and transport have been characterized. The local ABA concentration is critical for initiating ABA-mediated signalling during plant development and in response to environmental changes. In this chapter we discuss the mechanisms that regulate ABA biosynthesis, catabolism, transport and homoeostasis. We also present the findings of recent research on ABA perception by cellular receptors, and ABA signalling in response to cellular and environmental conditions.Cytokinin is an essential plant hormone that is involved in a wide range of plant growth and developmental processes which are controlled through its signalling pathway. Cytokinins are a class of molecules that are N(6)-substituted adenine derivatives, such as isopentenyl adenine, and trans- and cis-zeatin, which are common in most plants. The ability to perceive and respond to cytokinin occurs through a modified bacterial two-component pathway that functions via a multi-step phosphorelay. This cytokinin signalling process is a crucial part of almost all stages of plant life, from embryo patterning to apical meristem regulation, organ development and eventually senescence. The cytokinin signalling pathway involves the co-ordination of three types of proteins histidine kinase receptors to perceive the signal, histidine phosphotransfer proteins to relay the signal, and response regulators to provide signal output. This pathway contains both positive and negative elements that function in a complex co-ordinated manner to control cytokinin-regulated plant responses. Although much is known about how this cytokinin signal is perceived and initially regulated, there are still many avenues that need to be explored before the role of cytokinin in the control of plant processes is fully understood.The plant hormone auxin (indole-3-acetic acid, IAA) controls growth and developmental responses throughout the life of a plant. A combination of molecular, genetic and biochemical approaches has identified several key components involved in auxin signal transduction. Rapid auxin responses in the nucleus include transcriptional activation of auxin-regulated genes and degradation of transcriptional repressor proteins. The nuclear auxin receptor is an integral component of the protein degradation machinery. Although auxin signalling in the nucleus appears to be short and simple, recent studies indicate that there is a high degree of diversity and complexity, largely due to the existence of multigene families for each of the major molecular components. Current studies are attempting to identify interacting partners among these families, and to define the molecular mechanisms involved in the interactions. Future goals are to determine the levels of regulation of the key components of the transcriptional complex, to identify higher-order complexes and to integrate this pathway with other auxin signal transduction pathways, such as the pathway that is activated by auxin binding to a different receptor at the outer surface of the plasma membrane. In this case, auxin binding triggers a signal cascade that affects a number of rapid cytoplasmic responses. Details of this pathway are currently under investigation.An ultra performance liquid chromatography triple quadrupole mass spectrometry (LC-MS-MS) method for the quantification of 14 benzodiazepines and three sedative hypnotics is presented. The fast and inexpensive assay was developed for California's Orange County Crime Lab for use in antemortem (AM) and postmortem casework. The drugs were rapidly cleaned up from AM blood, postmortem blood, urine, liver, brain and stomach contents using DPX(®) Weak Anion Exchange (DPX WAX) tips fitted on a pneumatic extractor, which can process up to 48 samples at one time. Assay performance was determined for validation based on recommendations by the Scientific Working Group for Forensic Toxicology for linearity, limit of quantitation, limit of detection, bias, precision (within run and between run), dilution integrity, carry-over, selectivity, recovery, ion suppression and extracted sample stability. Linearity was verified using the therapeutic and toxic ranges of all 17 analytes. Final verification of the method was confirmed by four analysts using 20 blind matrix matched samples. All results were within 20% of each other and the expected value.

The aim of this article is to examine how the European Association of Cardiovascular Imaging (EACVI) and the American Society of Echocardiography (ASE) recommendations on the classification of diastolic dysfunction (DDF) are interpreted in the scientific community and to explore how variations in the DDF definition affect the reported prevalence.

A systematic review of studies citing the EACVI/ASE consensus document 'Recommendations for the evaluation of left ventricular diastolic function by echocardiography' was performed. The definition of DDF used in each study was recorded. Subsequently, several possible interpretations of the EACVI/ASE classification scheme were used to obtain DDF prevalence in a community-based sample (n = 714). In the systematic review, 60 studies were included. In 13 studies, no specification of DDF definition was presented, a one-level classification tree was used in 13, a two-level classification tree in 18, and in the remaining 16 studies, a DDF definition was presented but no grading of DDF was performed. Tetrazolium Red mouse In 17 studies, the DDF definition relied solely on early diastolic tissue velocity and/or left atrial size. In eight of these studies, a single parameter was used, in two studies the logical operator AND was used to combine two or more parameters, and the remaining seven studies used the logical operator OR. The resulting prevalence of DDF in the community-based sample varied from 12 to 84%, depending on the DDF definition used.

A substantial heterogeneity of definitions of DDF was evident among the studies reviewed, and the different definitions had a substantial impact on the reported prevalence of DDF.

A substantial heterogeneity of definitions of DDF was evident among the studies reviewed, and the different definitions had a substantial impact on the reported prevalence of DDF.Accurate annular sizing in transcatheter aortic valve implantation (TAVI) planning is essential. It is now widely recognized that the annulus is an oval structure in most patients, but it remains unclear if the annulus undergoes change in size and shape during the cardiac cycle that may impact prosthesis size selection. Our aim was to assess whether the aortic annulus undergoes dynamic conformational change during the cardiac cycle and to evaluate possible implications for prosthesis size selection. We performed a systematic search in PubMed and Embase databases and reviewed all available literature on aortic annulus measurements in at least two cardiac phases. Twenty-nine articles published from 2001 to 2014 were included. In total, 2021 subjects with and without aortic stenosis were evaluated with a mean age ranging from 11 ± 3.6 to 84.9 ± 7.2 years. Two- and three-dimensional echocardiography was performed in six studies each, magnetic resonance imaging was used in one and computed tomography in 17 studies. In general, the aortic annulus was more circular in systole and predominantly oval in diastole. Whereas the annular long-axis diameter showed insignificant change throughout the cycle, the short-axis diameter, area, and perimeter were significantly larger in systole compared with diastole. Hence, the aortic annulus does undergo dynamic changes during the cardiac cycle. In patients with large conformational changes, diastolic compared with systolic measurements can result in undersizing TAVI prostheses. Due to the complex annular anatomy and dynamic change, three-dimensional assessment in multiple phases has utmost importance in TAVI planning to improve prosthesis sizing.

Exercise testing is performed in patients with hypertrophic cardiomyopathy to evaluate blood pressure response, a risk factor for sudden cardiac death. The prognostic role of exercise gas exchange variables is unknown.

Between 1998 and 2010, 1898 patients (age 47±15 years, range 16-86 years; 67% male) with hypertrophic cardiomyopathy underwent cardiopulmonary exercise testing. A total of 178 (9.4%) patients reached the primary end point of all-cause mortality or heart transplant (death/transplant) during a median follow-up of 5.6 years (interquartile range 2.6-8.9), giving an annual event rate of 1.6% per person year. Peak oxygen consumption (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.77-0.88, P<0.001), ventilatory efficiency (adjusted HR 1.10, 95% CI 1.00-1.22, P=0.049), and ventilatory anaerobic threshold (adjusted HR 0.82, 95% CI 0.70-0.96, P=0.016) were predictors of the primary outcome after correction for age, sex, left atrial size, nonsustained ventricular tachycardia, and eoxygen consumption, predict death from heart failure.

To follow-up for 5 years thyroid status evolution in 127 girls with mild (TSH 5-10 mU/l) subclinical hypothyroidism (SH) of different etiologies.

The population was divided into two age-matched groups of 42 and 85 girls with either idiopathic (group A) or Hashimoto's thyroiditis (HT)-related SH (group B). Group B was in turn divided into three subgroups, according to whether SH was either isolated or associated with Turner syndrome (TS) or Down syndrome (DS).

At the end of follow-up the rate of girls who became euthyroid was higher in group A (61.9% vs 10.6%), whereas the rates of patients who remained SH (55.3% vs 26.2%), became overtly hypothyroid (30.6% vs 11.9%) or required levothyroxine (l-T4) therapy (63.5% vs 23.8%) were higher in group B. Among the girls of group B, the risk of remaining SH or developing overt hypothyroidism was higher in the subgroups with TS or DS than in those with isolated HT.

Long-term prognosis of mild and idiopathic SH is frequently benign, even though a l-T4 treatment may be needed throughout follow-up in almost a quarter of cases; long-term prognosis is different in the girls with either idiopathic or HT-related SH; and the association with either TS or DS impairs the outcome of HT-related SH.

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