Background: Aortic stenosis (AS) is associated with increasing severity of diastolic dysfunction as measured by conventional echocardiographic grading. The parameterized diastolic filling (PDF) method can describe diastolic function mechanistically, by analyzing filling using the physics of classical mechanics for spring recoil. Purpose: To use the PDF method to describe the mechanics of how diastolic dysfunction manifests in AS. Methods: Patients (n=73) undergoing echocardiography were included according to AS of varying severity (normal/mild AS: maximum Doppler velocity across aortic valve (Vmax) <3.0 m/s, moderate/severe AS: Vmax ≥3.0 m/s). Analysis of pulsed wave Doppler transmitral E-waves was performed using freely available software for PDF analysis. Results: Compared to normal/mild AS (n=41), patients with moderate/severe AS (n=32) had a left ventricle with a greater interventricular septal thickness (p=0.02) and higher E/é (p=0.007), but similar left ventricular ejection fraction (p=0.10) and left atrial volume index (p=0.21). PDF analysis (48 ± 9 E-waves per patient) showed that moderate/severe AS did not differ in myocardial stiffness (p=0.70), but had a higher myocardial viscoelasticity (p=0.02), higher load (p=0.04), longer derived time constant of isovolumetric pressure decay (tau, p=0.004), higher filling energy (p=0.02), higher peak driving (p=0.02) and resistive (p=0.004) force of filling, lower kinematic filling efficiency index (p<0.001), but no difference in the load-independent index of diastolic function (p=0.62). Conclusions: AS was primarily associated with a greater damping of LV recoil (viscoelasticity) and load, but without a change in myocardial stiffness. Diastolic dysfunction in AS manifests with pathophysiological changes that are mechanistically consistent with a greater severity of diastolic dysfunction. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The research was funded in part by the Swedish Research Council, Swedish Heart and Lung Foundation, Stockholm County Council, Karolinska Institutet, Heart Research Australia, New South Wales Health, and the University of Sydney. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the UnitingCare Health Human Research Ethics Committee (Ref: 2024.02.396) with a retrospective waiver of individual subject informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.
Background. Increased visceral adipose tissue (VAT) is strongly associated with cardiometabolic risk factors. Accurate quantification of VAT is available through magnetic resonance imaging (MRI), which incurs a significant financial and time burden. We aimed to assess the accuracy of dual-energy X-ray absorptiometry- (DXA-) derived VAT (DXA-VAT) against a gold standard MRI protocol (MRI-VAT) in children with normal weight and obesity cross-sectionally, and over the course of a lifestyle intervention. Methodology. MRI-VAT and DXA-VAT were quantified in 61 children (30 normal weight and 31 with obesity) at baseline. Children with obesity entered a three-month exercise and/or nutrition intervention after which VAT was reassessed. MRI- and DXA-VAT cross-sectional area, volume, and mass were quantified, and associations were calculated at baseline (n = 61) and pre-post intervention (n = 28, 3 participants dropped out). Method agreement was assessed through Bland–Altman analysis, linear regression, and Passing–Bablok regression. Results. At baseline, all DXA- and MRI-VAT outcomes were strongly associated (r = 0.90, P<0.001). However, there were no significant associations between absolute or relative change in DXA- and MRI-VAT outcomes (r = 0.25–0.36, P>0.05). DXA significantly overestimated VAT CSA (cross-sectional area), volume, and mass when compared with MRI (P<0.001) at baseline. Significant proportional bias was observed for all DXA-VAT outcomes at baseline and for relative longitudinal changes in DXA-VAT. Conclusions. Although DXA-VAT outcomes were strongly associated with MRI-VAT outcomes at baseline, estimates were subject to proportional bias in children with obesity and normal weight. DXA lacks validity for detecting changes in VAT among children with obesity. This trial is registered with NCT01991106.
Paediatric obesity significantly increases the risk of developing cardiometabolic diseases across the lifespan. Increasing cardiorespiratory fitness (CRF) could mitigate this risk. High-intensity interval training (HIIT) improves CRF in clinical adult populations but the evidence in paediatric obesity is inconsistent.
BACKGROUND:High intensity interval training (HIIT) confers superior cardiovascular health benefits to moderate intensity continuous training (MICT) in adults and may be efficacious for improving diminished cardiac function in obese children. The aim of this study was to compare the effects of HIIT, MICT and nutrition advice interventions on resting left ventricular (LV) peak systolic tissue velocity (S') in obese children. METHODS:Ninety-nine obese children were randomised into one of three 12-week interventions, 1) HIIT [n = 33, 4 × 4 min bouts at 85-95% maximum heart rate (HRmax), 3 times/week] and nutrition advice, 2) MICT [n = 32, 44 min at 60-70% HRmax, 3 times/week] and nutrition advice, and 3) nutrition advice only (nutrition) [n = 34]. RESULTS:Twelve weeks of HIIT and MICT were equally efficacious, but superior to nutrition, for normalising resting LV S' in children with obesity (estimated mean difference 1.0 cm/s, 95% confidence interval 0.5 to 1.6 cm/s, P < 0.001; estimated mean difference 0.7 cm/s, 95% confidence interval 0.2 to 1.3 cm/s, P = 0.010, respectively). CONCLUSIONS:Twelve weeks of HIIT and MICT were superior to nutrition advice only for improving resting LV systolic function in obese children.
Background Obesity in childhood predisposes individuals to cardiovascular disease and increased risk of premature all-cause mortality. The aim of this study was to determine differences in LV morphology and function in obese and normal-weight adolescents. Furthermore, relationships between LV outcomes, cardiorespiratory fitness (CRF) and adiposity were explored. Methods LV morphology was assessed using magnetic resonance imaging (MRI) in 20 adolescents (11 normal-weight [BMI equivalent to 18 kg/m2–25 kg/m2] and 9 obese [BMI equivalent to ≥30 kg/m2]); 13.3 ± 1.1 years, 45% female, Tanner puberty stage 3 [2–4]) using magnetic resonance imaging (MRI). Global longitudinal strain (GLS), strain rate (SR) and traditional echocardiographic indices were used to assess LV function. CRF (peak oxygen consumption), percent body fat (dual-energy x-ray absorptiometry), abdominal adipose tissue (MRI), and blood biochemistry markers were also evaluated. Results Adolescents with obesity showed significantly poorer LV function compared to normal-weight adolescents (P < 0.05) indicated by higher GLS (+6.29%) and SR in systole (+0.17 s−1), and lower SR in early diastole (−0.61 s−1), and tissue Doppler velocities (S′ −2.7 cm/s; e′ −2.3 cm/s; A′ −1.1 cm/s). There were no group differences in LV morphology when indexed to fat free mass (P > 0.05). Moderate to strong associations between myocardial contractility and relaxation, adiposity, arterial blood pressure and cardiorespiratory fitness were noted (r = 0.49–0.71, P < 0.05). Conclusion Obesity in adolescence is associated with altered LV systolic and diastolic function. The notable relationship between LV function, CRF and adiposity highlights the potential utility of multidisciplinary lifestyle interventions to treat diminished LV function in this population. Clinical trial registration: NCT01991106.
Cardiac amyloidosis is a rare but serious condition with poor survival. One of the early findings by echocardiography is impaired diastolic function, even before the development of cardiac symptoms. Early diagnosis is important, permitting initiation of treatment aimed at improving survival. The parameterized diastolic filling (PDF) formalism entails describing the left ventricular filling pattern during early diastole using the mathematical equation for the motion of a damped harmonic oscillator. We hypothesized that echocardiographic PDF analysis could detect differences in diastolic function between patients with amyloidosis and controls. Pulsed-wave Doppler echocardiography of transmitral flow was measured in 13 patients with amyloid heart disease and 13 age-and gender matched controls. E-waves (2 to 3 per subject) were analyzed using in-house developed software. Nine PDF-derived parameters were obtained in addition to conventional echocardiographic parameters of diastolic function. Compared to controls, cardiac amyloidosis patients had a larger left atrial area (23.7 +/- 7.5 cm(2) vs. 18.5 +/- 4.8 cm(2), p = 0.04), greater interventricular septum wall thickness (14.4 +/- 2.6 mm vs. 9.3 +/- 1.3 mm, p < 0.001), lower e' (0.06 +/- 0.02 m/s vs. 0.09 +/- 0.02m/s, p < 0.001) and higher E/e' (18.0 +/- 12.9 vs. 7.7 +/- 1.3, p = 0.001). The PDF parameter peak resistive force was greater in cardiac amyloidosis patients compared to controls (17.9 +/- 5.7 mN vs. 13.1 +/- 3.1 mN, p = 0.03), and other PDF parameters did not differ. PDF analysis revealed that patients with cardiac amyloidosis had a greater peak resistive force compared to controls, consistent with a greater degree of diastolic dysfunction. PDF analysis may be useful in characterizing diastolic function in amyloid heart disease. (E-mail: martin.ugander@gmail.com) (C) 2017 World Federation for Ultrasound in Medicine & Biology.
PURPOSE:Poor cardiorespiratory fitness is associated with increased all cause morbidity and mortality. In children with obesity, maximum oxygen uptake (V̇O2max) may not be achieved due to reduced motivation and peripheral fatigue. We aimed to identify a valid submaximal surrogate for V̇O2max in children with obesity.METHOD:Ninety-two children with obesity (7-16 years) completed a maximal exercise treadmill test and entered a three-month exercise and/or nutrition intervention after which the exercise test was repeated (n = 63). Participants were required to reach V̇O2max to be included in this analysis (n = 32 at baseline and n = 13 at both time-points). The oxygen uptake efficiency slope (OUES) was determined as the slope of the line when V̇O2 (L/min) was plotted against log V̇E. Associations between the maximal OUES, submaximal OUES (at 3, 4, 5 and 6 min of the exercise test) and V̇O2max were calculated.RESULTS:In the cross-sectional analysis, V̇O2max (L/min) was strongly correlated with 5-min OUES independent of Tanner puberty stage and sex (R2 = .80, p < .001). Longitudinal changes in V̇O2max were closely reflected by changes in 5-min OUES independent of change in percent body fat (R2 = .63, p < .05).CONCLUSION:The 5-min OUES is a viable alternative to V̇O2max when assessing children with obesity.
An improvement in cardiorespiratory fitness (CRF) following an exercise intervention is a primary indicator of training efficacy. In obese children, maximal oxygen uptake (VO2max) may not be achieved during an exercise test due to reduced motivation or peripheral fatigue. Identifying a valid surrogate for VO2max, obtained with a submaximal exercise effort, would therefore be advantageous in this population. PURPOSE: To determine whether exercise-training induced changes in VO2max are associated with changes in a submaximal six-minute oxygen uptake efficiency slope (6minOUES) protocol in obese children. METHODS: Sixty-three obese children (BMI>95th percentile for age & sex) completed a maximal exercise treadmill test with ventilatory expired gas analysis before and after a three-month exercise intervention. Participants who satisfied oxygen uptake plateau criteria and achieved a peak respiratory exchange ratio (RER) ≥1.05 were classified as reaching VO2max. Thirteen participants (age 13.0±2.0; Tanner puberty stage 3 (2.5-4.5), female 69%) reached VO2max prior to and following the intervention and were included in this analysis. The OUES was determined as the slope of the line when VO2 (ml/min) was plotted against logVE. Maximal OUES (OUESmax) was calculated from start to end of the test while 6minOUES was calculated from start of the test to the 6-minute marker. Body fat percentage was quantified using dual x-ray absorptiometry or air displacement plethysmography. VO2max, OUESmax and 6minOUES were normalised to body weight and change scores were calculated. RESULTS: There was an increase in VO2max of 2.85±5.48 ml/kg/min following a three-month exercise intervention. This was closely reflected by a mean increase in OUESmax (3.45±7.60) and 6minOUES (3.62±8.49). The increase in VO2max was strongly correlated with an increase in OUESmax (r2 = 0.81, p<0.05) and an increase in 6minOUES (r2 = 0.77, p<0.05) independent of sex and change in percent body fat. The increase in 6minOUES was strongly correlated with the increase in OUESmax (r2 = 0.91, p<0.05). CONCLUSION: The 6minOUES treadmill protocol is a valid submaximal measure of exercise-training induced CRF changes in obese children. This may be valuable when VO2max is not achieved in exercise testing designed to determine training-induced improvements.
Poor cardiorespiratory fitness (CRF) is associated with increased all cause morbidity and mortality. CRF assessment in obese youth provides valuable information on present and future health status as well as assessing efficacy of an exercise intervention. Maximal oxygen uptake (VO2max) is often difficult to achieve in a sedentary paediatric population due to a lack of motivation and peripheral fatigue, resulting in submaximal test results. Due to the tight linear relationship throughout exercise, the oxygen uptake efficiency slope (OUES) holds possible utility as a predictor of VO2max. PURPOSE: To determine whether a submaximal six-minute OUES (6minOUES) protocol accurately predicts maximal oxygen uptake (VO2max) in obese children. METHODS: Eighty-nine obese children (BMI>95th percentile for age and sex) completed a maximal graded exercise treadmill test with ventilatory expired gas analysis. Participants who satisfied oxygen uptake plateau criteria and achieved a peak respiratory exchange ratio (RER) ≥1.05 were classified as reaching VO2max and were included in this analysis. The OUES was determined as the slope of the line when VO2 (ml/min) was plotted against logVE. Maximal OUES (OUESmax) was calculated from start to end of the test while 6-minute OUES (6minOUES) was calculated from start of the test to the 6-minute time-point. A multivariate linear regression was used to determine the relationship between VO2max, 6minOUES, and OUESmax, as well as to derive a prediction equation for VO2max. RESULTS: Thirty-two obese children (age 12.4±1.9; Tanner puberty stage 3 (2-4), female 59%) achieved a VO2max of 31.2±5.5 ml/kg/min. Participants attained an OUESmax of 2.82±0.89 and a 6minOUES of 2.77±1.01. VO2max (L/min) was strongly correlated with OUESmax in L/min (r2 = 0.93, p<0.001) and 6minOUES in L/min (r2 = 0.83, p<0.001) independent of Tanner stage and sex. Furthermore, 6minOUES was strongly correlated with OUESmax (r2 = 0.91, p<0.001). The VO2max prediction equation derived from this cohort is as follows: VO2max= 0.651*6minOUES + 0.026*Tanner Stage + 0.565 (r = 0.90, standard error of the estimate = 0.34). CONCLUSIONS: The 6minOUES treadmill protocol may be used to predict VO2max in obese children when oxygen uptake plateau criteria and peak RER indicate submaximal exercise performance.
INTRODUCTION:The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. METHODS AND ANALYSIS:Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. ETHICS AND DISSEMINATION:This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. TRIAL REGISTRATION NUMBER:NCT01991106.
Background: Transoesophageal echocardiography (TOE) guided direct current cardioversion (DCCV) following variable duration anticoagulation has become the modern standard of care for many patients with atrial fibrillation. Agents used include warfarin, heparins, and more recently dabigatran and rivaroxaban. During a single anaesthetic, if TOE can rule out left atrial appendage (LAA) thrombus in recently anticoagulated patients, the patient is cardioverted. Historical data from the 1990s prior to routine anticoagulation for cardioversion suggested LAA thrombus rates of approximately 14%. Whilst new anticoagulant agents have been safely used for TOE-guided DCCV, rates of LAA thrombus in the modern era have not been reported. Methods: Data from 640 patients listed for TOE/DCCV with adequate anticoagulation on the day (but with variable duration) were reviewed. All cases where thrombus was identified and DCCV deferred had independent blinded retrospective review of the TOE images (compressed stored DICOM data). Results: Left atrial appendage thrombus causing cancellation of DCCV was identified in 34/640 patients (5.3%). Of these, 23/34 were anticoagulated with standard warfarin/heparin, 9/34 with dabigatran and 2/34 with Rivaroxaban. Interobserver variability amongst four senior TOE cardiologists agreed only to a moderate extent as to the presence of LAA thrombus (binary scale "more likely present" vs "more likely absent"), kappa = 0.46, P < 0.00005. Conclusions: LAA thrombus remains surprisingly highly prevalent in anticoagulated patients scheduled for DCCV. Because of the high leverage risk/benefit ratio "missing a clot" (false negative), interobserver variability was relatively high when studies were reviewed retrospectively.
A cpSRP [chloroplast SRP (signal recognition particle)] comprising cpSRP54 and cpSRP43 subunits mediates the insertion of light-harvesting proteins into the thylakoid membrane. We dissected its interaction with a full-length membrane protein substrate in aqueous solution by insertion of site-specific photo-activatable cross-linkers into in vitro-synthesized Lhcb1 (major light-harvesting chlorophyll-binding protein of photosystem II). We show that Lhcb1 residues 166-176 cross-link specifically to the cpSRP43 subunit. Some cross-link positions within Lhcb1 are in the 'L18' peptide required for targeting of cpSRP substrates, whereas other cross-linking positions define a new targeting signal in the third transmembrane span. Lhcb1 was not found to cross-link to cpSRP54 at any position, and cross-linking to cpSRP43 is unaffected by the absence of cpSRP54. cpSRP43 thus effectively binds substrates autonomously, and its ability to independently bind an extended 20+-residue substrate region highlights a major difference with other SRP types where the SRP54 subunit binds to hydrophobic target sequences. The results also show that cpSRP43 can bind to a hydrophobic, three-membrane span, substrate in aqueous solution, presumably reflecting a role for cpSRP in the chloroplast stroma. This mode of action, and the specificity of the cpSRP43-substrate interaction, may be associated with cpSRP's unique post-translational mode of action.
Background: The "sparkled" echocardiographic appearance of amyloid has become less visually obvious in the era of harmonic imaging. Significantly dilated atria in the setting of a normal sized ventricle may be another easy visual marker for cardiac amyloidosis.Methods: A retrospective analysis of echocardiograms of patients with biopsy-proven cardiac amyloid compared with patients with hypertension was conducted. There were 36 patients in each group, and they were matched for left ventricular wall thickness, as well as age and sex.Results: Patients with cardiac amyloid had significantly larger atria than the group with hypertension (left atrial areas 29 cm(2) versus 19 cm(2), p<0.001, AUC 0.84, volumes 100 cm(3) versus 55 cm(3), p < 0.001, AUC 0.915). A volume of 69 cm(3) produced a specificity and sensitivity of 85% for amyloidosis.Conclusions: Atrial dilatation can be used as a visual marker for cardiac amyloidosis. This may be a simple visual method to differentiate this infiltrative cardiomyopathy from left ventricular hypertrophy. (Heart, Lung and Circulation (2011);20:574-578) (C) 2011 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier Inc. All rights reserved.
Background: The time course of regional functional recovery following revascularization with regards to the presence or absence of infarction is poorly known. We studied the effect of the presence of chronic nontransmural infarction on the time course of recovery of myocardial perfusion and function after elective revascularization.Methods: Eighteen patients (mean age 69, range 52-84, 17 men) prospectively underwent cine magnetic resonance imaging (MRI), delayed contrast enhanced MRI and rest/stress 99m-Tc-tetrofosmin single photon emission computed tomography (SPECT) before, one and six months after elective coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI).Results: Dysfunctional myocardial segments (n = 337/864, 39%) were classified according to the presence (n = 164) or absence (n = 173) of infarction. Infarct transmurality in dysfunctional segments was largely non-transmural (transmurality = 31 +/- 22%). Quantitative stress perfusion and wall thickening increased at one month in dysfunctional segments without infarction (p < 0.001), with no further improvement at six months. Despite improvements in stress perfusion at one month (p < 0.001), non-transmural infarction displayed a slower and lesser improvement in wall thickening at one (p < 0.05) and six months (p < 0.001).Conclusions: Dysfunctional segments without infarction represent repetitively stunned or hibernating myocardium, and these segments improved both perfusion and function within one month after revascularization with no improvement thereafter. Although dysfunctional segments with non-transmural infarction improved in perfusion at one month, functional recovery was mostly seen between one and six months, possibly reflecting a more severe ischemic burden. These findings may be of value in the clinical assessment of regional functional recovery in the time period after revascularization.
Thioredoxins play key regulatory roles in chloroplasts by linking photosynthetic light reactions to a series of plastid functions. In addition to the established groups of thioredoxins, f, m, x, and y, novel plant thioredoxins were also considered to include WCRKC motif proteins, CDSP32, the APR proteins, the lilium proteins and HCF164. Despite their important roles, the subcellular locations of many novel thioredoxins has remained unknown. Here, we report a study of their subcellular location using the cDNA clone resources of TAIR. In addition to filling all gaps in the subcellular map of the established chloroplast thioredoxins f, m, x and y, we show that the members of the WCRKC family are targeted to the stroma and provide evidence for a stromal location of the lilium proteins. The combined data from this and related studies indicate a consistent stromal location of the known Arabidopsis chloroplast thioredoxins except for thylakoid-bound HCF164.
Abstract Background Knowledge about age-specific normal values for left ventricular mass (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) by cardiac magnetic resonance imaging (CMR) is of importance to differentiate between health and disease and to assess the severity of disease. The aims of the study were to determine age and gender specific normal reference values and to explore the normal physiological variation of these parameters from adolescence to late adulthood, in a cross sectional study. Methods Gradient echo CMR was performed at 1.5 T in 96 healthy volunteers (11–81 years, 50 male). Gender-specific analysis of parameters was undertaken in both absolute values and adjusted for body surface area (BSA). Results Age and gender specific normal ranges for LV volumes, mass and function are presented from the second through the eighth decade of life. LVM, ESV and EDV rose during adolescence and declined in adulthood. SV and EF decreased with age. Compared to adult females, adult males had higher BSA-adjusted values of EDV (p = 0.006) and ESV (p < 0.001), similar SV (p = 0.51) and lower EF (p = 0.014). No gender differences were seen in the youngest, 11–15 year, age range. Conclusion LV volumes, mass and function vary over a broad age range in healthy individuals. LV volumes and mass both rise in adolescence and decline with age. EF showed a rapid decline in adolescence compared to changes throughout adulthood. These findings demonstrate the need for age and gender specific normal ranges for clinical use.
We describe a novel, typically prokaryotic, sensor kinase in chloroplasts of green plants. The gene for this chloroplast sensor kinase (CSK) is found in cyanobacteria, prokaryotes from which chloroplasts evolved. The CSK gene has moved, during evolution, from the ancestral chloroplast to the nuclear genomes of eukaryotic algae and green plants. The CSK protein is now synthesised in the cytosol of photosynthetic eukaryotes and imported into their chloroplasts as a protein precursor. In the model higher plant Arabidopsis thaliana, CSK is autophosphorylated and required for control of transcription of chloroplast genes by the redox state of an electron carrier connecting photosystems I and II. CSK therefore provides a redox regulatory mechanism that couples photosynthesis to gene expression. This mechanism is inherited directly from the cyanobacterial ancestor of chloroplasts, is intrinsic to chloroplasts, and is targeted to chloroplast genes.
Secretory and membrane proteins carry amino-terminal signal sequences that, in cotranslational targeting, are recognized by the signal recognition particle protein SRP54 without sequence specificity. The most abundant membrane proteins on Earth are the light-harvesting chlorophyll a/b binding proteins (LHCPs). They are synthesized in the cytoplasm, imported into the chloroplast, and posttranslationally targeted to the thylakoid membrane by cpSRP, a heterodimer formed by cpSRP54 and cpSRP43. We present the 1.5 angstrom crystal structure of cpSRP43 characterized by a unique arrangement of chromodomains and ankyrin repeats. The overall shape and charge distribution of cpSRP43 resembles the SRP RNA, which is absent in chloroplasts. The complex with the internal signal sequence of LHCPs reveals that cpSRP43 specifically recognizes a DPLG peptide motif. We describe how cpSPR43 adapts the universally conserved SRP system to posttranslational targeting and insertion of the LHCP family of membrane proteins.
Objectives. To find the time-to-peak for creatine kinase MBmass (CKMB) and cardiac troponin T (cTnT) after acute reperfusion, to compare peak and cumulative values to estimate infarct size (IS), and to evaluate clinical routine sampling for assessment of IS. Design. Acute primary percutaneous coronary intervention (PCI) was performed in 38 patients with first-time myocardial infarction. In 21 patients, CKMB and cTnT were acquired before PCI and at 1.5, 3, 6, 12, 18, 24, and 48 hours thereafter. In 17 patients, clinical routine samples were acquired at arrival, and at 10 and 20 h. IS was assessed by delayed contrast-enhanced MRI (DE- MRI). Results. Time-to-peak was 7.6 +/- 3.6 h for CKMB and 8.1 +/- 3.4 h for cTnT. Peak values correlated strongly to cumulative values (r(s) = 0.97-0.98) as well as to DE-MRI (r(s) = 0.8 - 0.82). Clinical routine sampling showed lower r(s) values (0.47 - 0.60). Conclusions. Peak values are likely captured if CKMB and cTnT are acquired at 3, 6, and 12 h after acute PCI. These peak values can be used to estimate myocardial infarct size after acute PCI.