The Molecular Frequency, Conservation and Role of Reactive Cysteines in Plant Lipid Metabolism.

Cysteines (Cys) are chemically reactive amino acids containing sulfur that play diverse roles in plant biology. Recent proteomics investigations in Arabidopsis thaliana have revealed the presence of thiol post-translational modifications (PTMs) in several Cys residues. These PTMs are presumed to impact protein structure and function, yet mechanistic data regarding the specific Cys susceptible to modification and their biochemical relevance remain limited. To help address these limitations, we have conducted a wide-ranging analysis by integrating published datasets encompassing PTM proteomics (comparing S-sulfenylation, persulfidation, S-nitrosylation and S-acylation), genomics and protein structures, with a specific focus on proteins involved in plant lipid metabolism. The prevalence and distribution of modified Cys residues across all analyzed proteins is diverse and multifaceted. Nevertheless, by combining an evaluation of sequence conservation across 100+ plant genomes with AlphaFold-generated protein structures and physicochemical predictions, we have unveiled structural propensities associated with Cys modifications. Furthermore, we have identified discernible patterns in lipid biochemical pathways enriched with Cys PTMs, notably involving beta-oxidation, jasmonic acid biosynthesis, fatty acid biosynthesis and wax biosynthesis. These collective findings provide valuable insights for future investigations targeting the mechanistic foundations of Cys modifications and the regulation of modified proteins in lipid metabolism and other metabolic pathways.

Imaging plant metabolism in situ.

Mass spectrometry imaging (MSI) has emerged as an invaluable analytical technique for investigating the spatial distribution of molecules within biological systems. In the realm of plant science, MSI is increasingly employed to explore metabolic processes across a wide array of plant tissues, including those in leaves, fruits, stems, roots, and seeds, spanning various plant systems such as model species, staple and energy crops, and medicinal plants. By generating spatial maps of metabolites, MSI has elucidated the distribution patterns of diverse metabolites and phytochemicals, encompassing lipids, carbohydrates, amino acids, organic acids, phenolics, terpenes, alkaloids, vitamins, pigments, and others, thereby providing insights into their metabolic pathways and functional roles. In this review, we present recent MSI studies that demonstrate the advances made in visualizing the plant spatial metabolome. Moreover, we emphasize the technical progress that enhances the identification and interpretation of spatial metabolite maps. Within a mere decade since the inception of plant MSI studies, this robust technology is poised to continue as a vital tool for tackling complex challenges in plant metabolism.

Outcomes of patients undergoing edge-to-edge mitral valve repair with the Edwards PASCAL transcatheter valve repair system under conscious sedation.

BACKGROUND: The development of the PASCAL transcatheter valve repair system for treating mitral regurgitation (MR) greatly extends therapeutic options. AIMS: To assess the safety, efficacy, and time efficiency of the PASCAL system in transcatheter edge-to-edge repair (TEER) under conscious sedation (CS). METHODS: This is a retrospective, two-center, German registry study consisting of 211 patients who underwent TEER using the PASCAL system under CS. The endpoints were to assess (1) technical, device, and procedural success as per Mitral Valve Academic Research Consortium (MVARC), (2) conversion rate to general anesthesia (GA), (3) hospital length of stay (LoS), (4) New York Heart Association (NYHA) class, and (5) MR compared to baseline at 30-day. RESULTS: A total of 211 patients with a mean age of 78.4 ± 8.9 years, with 51.4% being female and 86.7% belonging to NYHA functional class III/IV and EuroSCORE II 6.3 ± 4.9%, were enrolled. Procedural success attained was 96.9%, and six patients (2.8%) required conversion from CS to GA. At 30 days follow-up, a significant improvement in MR was found in 96 patients (54.2%) patients with 0/1 grade MR and 45 patients (29.5%) were in NYHA functional class III + IV. Moreover, TEER under CS has a short hospital LoS (6.71 ± 5.29 days) and intensive care unit LoS (1.34 ± 3.49 days) with a 2.8% mortality rate. CONCLUSIONS: Performing TEER with the PASCAL system under CS resulted in appreciable (96.9%) procedural success with low mortality and is a safe and promising alternative to GA with positive clinical outcomes.

Seeing plants as never before.

Imaging has long supported our ability to understand the inner life of plants, their development, and response to a dynamic environment. While optical microscopy remains the core tool for imaging, a suite of novel technologies is now beginning to make a significant contribution to visualize plant metabolism. The purpose of this review was to provide the scientific community with an overview of current imaging methods, which rely variously on either nuclear magnetic resonance (NMR), mass spectrometry (MS) or infrared (IR) spectroscopy, and to present some examples of their application in order to illustrate their utility. In addition to providing a description of the basic principles underlying these technologies, the review discusses their various advantages and limitations, reveals the current state of the art, and suggests their potential application to experimental practice. Finally, a view is presented as to how the technologies will likely develop, how these developments may encourage the formulation of novel experimental strategies, and how the enormous potential of these technologies can contribute to progress in plant science.

Clinical outcomes of hundred large Impella implantations in cardiogenic shock patients based on individual clinical scenarios.

BACKGROUND: Large Impella systems (5.0 or 5.5; i.e., Impella 5+) (Abiomed Inc., Danvers, MA, USA) help achieve better clinical outcomes through relevant left ventricular unloading in acute cardiogenic shock (CS). Here, we report our experience with Impella 5+, while focusing on the clinical outcomes depending on individual case scenarios in patients with acute CS. METHODS: This single-center retrospective observational study included 100 Impella 5+ implantations conducted on patients with acute CS from November 2018 to October 2021. After excluding 10 reimplantation cases, 90 cases were enrolled for further analysis. RESULTS: In-hospital and 30-day mortality rates were 56.7% (n = 51) and 48.9% (n = 44), respectively. In-hospital mortality was lower in patients with acute myocardial infarction (AMI) than in non-AMI patients (p = 0.07). Young age and low lactate levels were the independent predictors of successful transition and survival after permanent mechanical circulatory support/heart transplantation (pMCS/HTX) (age, p = 0.03; lactate level, p = 0.04; survived after pMCS/HTX, n = 11; died on Impella, n = 41). During simultaneous utilization of venoarterial extracorporeal membrane oxygenation therapy and Impella 5+, termed ECMELLA therapy, high dose of noradrenaline was a predictive factor for in-hospital mortality by multivariate analysis (n = 0.02). CONCLUSIONS: Our results suggest that enhanced Impella support might have better clinical outcomes among acute CS patients supported with large Impella, those with AMI than those with no AMI. Young age and low lactate levels were predictors of successful bridging to pMCS/HTX and favorable clinical outcomes thereafter. The clinical outcomes of ECMELLA therapy might depend on noradrenaline dose at the time of Impella 5+ implantation.

Comparison of costs associated with transcatheter mitral valve repair: PASCAL vs MitraClip in a real-world setting.

AIMS: We aimed to conduct a clinical process cost analysis to evaluate all upcoming costs of mitral valve transcatheter edge-to-edge repair (M-TEER) treatment using the MitraClip and the PASCAL repair system. METHODS: First, we prospectively enrolled 107 M-TEER patients treated with either the PASCAL or MitraClip system and compared all upcoming costs during the M-TEER procedure and the associated in-hospital stay. Second, we retrospectively analysed 716 M-TEER procedures with regard to the occurrence of complications and their associated costs. All materials used in the catheterization laboratory for the procedures were evaluated. The cost analysis considered various expenses, such as general in-hospital costs, device costs, catheter laboratory and material costs. RESULTS: In the prospective study, 51 patients were treated using the PASCAL system, and 56 were treated using the MitraClip system. The two groups had comparable baseline characteristics and comorbidities. The total in-hospital costs were 25 414 (Interquartile range (IQR) 24 631, 27 697) € in the PASCAL group and 25 633 (IQR 24 752, 28 256) € in the MitraClip group (p = 0.515). The major cost driver was initial material expenditure, mostly triggered by device costs, which were similar to the PASCAL and MitraClip systems. Overall intensive care unit and general ward costs did not differ between the PASCAL and MitraClip groups. In the retrospective analysis, M-TEER-related complications were rare but were associated with higher costs, mainly due to prolonged hospitalisation. CONCLUSION: The major cost driver of M-TEER was the material expenditure, which was mostly triggered by high device costs. The costs of treating patients were similar for the PASCAL and MitraClip systems. M-TEER-related complications are associated with higher costs, mainly due to prolonged hospitalisation. This analysis provides valuable insights into reducing expenses by modifying the process of M-TEER.

Genetically-determined variations in photosynthesis indicate roles for specific fatty acid species in chilling responses.

Using a population of recombinant inbred lines (RILs) cowpea (Vigna unguiculata. L. Walp), we tested for co-linkages between lipid contents and chilling responses of photosynthesis. Under low-temperature conditions (19°C/13°C, day/night), we observed co-linkages between quantitative trait loci intervals for photosynthetic light reactions and specific fatty acids, most strikingly, the thylakoid-specific fatty acid 16:1Δ3trans found exclusively in phosphatidylglycerol (PG 16:1t). By contrast, we did not observe co-associations with bulk polyunsaturated fatty acids or high-melting-point-PG (sum of PG 16:0, PG 18:0 and PG 16:1t) previously thought to be involved in chilling sensitivity. These results suggest that in cowpea, chilling sensitivity is modulated by specific lipid interactions rather than bulk properties. We were able to recapitulate the predicted impact of PG 16:1t levels on photosynthetic responses at low temperature using mutants and transgenic Arabidopsis lines. Because PG 16:1t synthesis requires the activity of peroxiredoxin-Q, which is activated by H2 O2 and known to be involved in redox signalling, we hypothesise that the accumulation of PG 16:1t occurs as a result of upstream effects on photosynthesis that alter redox status and production of reactive oxygen species.

The extracellular matrix proteins type I collagen, type III collagen, fibronectin, and laminin 421 stimulate migration of cancer cells.

For metastasis formation, individual cells from a primary tumor must migrate toward other tissues. The aim of this study was to determine if mesenchymal stromal cells (MSCs) from human bone marrow are able to emit signals that induce this migratory activity in cancer cells. We separated the supernatant of MSCs derived from human bone marrow by size-exclusion and ion-exchange chromatography and have subsequently studied the migratory behavior of the prostate cancer cell line PC3 and the breast cancer cell line MDA-MB-231 toward the respective fractions in a transwell migration assay. We identified the extracellular matrix (ECM) proteins type I collagen, type III collagen, fibronectin, and laminin 421 as potential drivers of cancer cell migration. These results could be reproduced using the corresponding isolated or recombinant ECM proteins. Knockdown of the gene encoding beta 1 integrin, an important cell surface receptor for fibronectin, has led to inhibition of cancer cell migration. This supports the hypothesis that beta 1 integrin signaling represents an initial event that leads to metastasis, and that signaling is triggered by binding of integrin heterodimers to ECM molecules. Further characterization of signaling factors and their respective receptors will have implications for anticancer drug development.

Donor hypernatremia is associated with increased mortality after heart transplantation: A retrospective study.

BACKGROUND AND AIMS: Donor hypernatremia has been associated with primary graft dysfunction in heart transplantation (HTx) and is correlated with impaired outcome following liver and renal transplantation. However, controversial data exist regarding the impact of sodium dysregulation on survival. This study aims to investigate the impact of donor sodium levels on early morbidity and short- and midterm survival following HTx. METHODS: Between September 2010 and June 2021, a total of n = 218 patients underwent HTx in our center. From those, 214 could be included retrospectively in our study. For each donor, sodium levels were collected and different cut-off levels from 145 to 159 mmol/L were investigated by Kaplan-Meier-analysis. Then, recipients were divided in three groups regarding donor sodium: Normonatremia (133-145 mmol/L, n = 73), mild hypernatremia (146-156 mmol/L, n = 105) and severe hypernatremia (>156 mmol/L, n = 35). Recipient and donor variables were reviewed and compared, including peri- and postoperative characteristics and recipient survival after up to 5 years after transplantation. RESULTS: All patients were comparable regarding baseline characteristics and perioperative parameters. Regarding early mortality, 90-day survival was significantly reduced only in patients with severe donor hypernatremia in comparison to normonatremia (90% vs. 71%, p = .02), but not in mild hypernatremia (89%, p = .89). One-year survival was comparable in all groups (p > .28). CONCLUSION: Severe donor hypernatremia was associated with reduced short-term survival, while the correlation weakens > 1 year after HTx. As our study is limited due to the nature of its retrospective, single-center approach, future prospective studies are needed to evaluate the importance of donor management with regard to hypernatremia.

PEROXIREDOXIN Q stimulates the activity of the chloroplast 16:1Δ3trans FATTY ACID DESATURASE4.

Thylakoid membrane lipids, comprised of glycolipids and the phospholipid phosphatidylglycerol (PG), are essential for normal plant growth and development. Unlike other lipid classes, chloroplast PG in nearly all plants contains a substantial fraction of the unusual trans fatty acid 16:1Δ3trans or 16:1t. We determined that, in Arabidopsis thaliana, 16:1t biosynthesis requires both FATTY ACID DESATURASE4 (FAD4) and a thylakoid-associated redox protein, PEROXIREDOXIN Q (PRXQ), to produce wild-type levels of 16:1t. The FAD4-PRXQ biochemical relationship appears to be very specific in planta, as other fatty acids (FA) desaturases do not require peroxiredoxins for their activity, nor does FAD4 require other chloroplast peroxiredoxins under standard growth conditions. Although most of chloroplast PG assembly occurs at the inner envelope membrane, FAD4 was primarily associated with the thylakoid membranes facing the stroma. Furthermore, co-production of PRXQ with FAD4 was required to produce Δ3-desaturated FAs in yeast. Alteration of the redox state of FAD4 or PRXQ through site-directed mutagenesis of conserved cysteine residues impaired Δ3 FA production. However, these mutations did not appear to directly alter disulfide status of FAD4. These results collectively demonstrate that the production of 16:1t is linked to the redox status of the chloroplast through PRXQ associated with the thylakoids.

The Microalga Nannochloropsis during Transition from Quiescence to Autotrophy in Response to Nitrogen Availability.

The marine microalgae Nannochloropsis oceanica (CCMP1779) is a prolific producer of oil and is considered a viable and sustainable resource for biofuel feedstocks. Nitrogen (N) availability has a strong impact on the physiological status and metabolism of microalgal cells, but the exact nature of this response is poorly understood. To fill this gap we performed transcriptomic profiling combined with cellular and molecular analyses of N. oceanica CCMP1779 during the transition from quiescence to autotrophy. N deprivation-induced quiescence was accompanied by a strong reorganization of the photosynthetic apparatus and changes in the lipid homeostasis, leading to accumulation of triacylglycerol. Cell cycle activation and re-establishment of photosynthetic activity observed in response to resupply of the growth medium with N were accompanied by a rapid degradation of triacylglycerol stored in lipid droplets (LDs). Besides observing LD translocation into vacuoles, we also provide evidence for direct interaction between the LD surface protein (NoLDSP) and AUTOPHAGY-RELATED8 (NoATG8) protein and show a role of microlipophagy in LD turnover in N. oceanica CCMP1779. This knowledge is crucial not only for understanding the fundamental mechanisms controlling the cellular energy homeostasis in microalgal cells but also for development of efficient strategies to achieve higher algal biomass and better microalgal lipid productivity.

Predictors of functional mitral regurgitation recurrence after percutaneous mitral valve repair.

We aimed to identify predictors of mitral regurgitation recurrence (MR) after percutaneous mitral valve repair (PMVR) in patients with functional mitral regurgitation (FMR). Patients with FMR were enrolled who underwent PMVR using the MitraClip® device. Procedural success was defined as reduction of MR of at least one grade to MR grade ≤ 2 + assessed at discharge. Recurrence of MR was defined as MR grade 3 + or worse at one year after initially successful PMVR. A total of 306 patients with FMR underwent PMVR procedure. In 279 out of 306 patients (91.2%), PMVR was successfully performed with MR grade ≤ 2 + at discharge. In 11.4% of these patients, MR recurrence of initial successful PMVR after 1 year was observed. Recurrence of MR was associated with a higher rate of heart failure rehospitalization during the 12 months follow-up (52.0% vs. 30.3%; p = 0.029), and less improvement in New York Heart Association (NYHA) functional class [68% vs. 19% of the patients presenting with NYHA functional class III or IV one year after PMVR when compared to patients without recurrence (p = 0.001)]. Patients with MR recurrence were characterized by a higher left ventricular sphericity index {0.69 [Interquartile range (IQR) 0.64, 0.74] vs. 0.65 (IQR 0.58, 0.70), p = 0.003}, a larger left atrium volume [118 (IQR 96, 143) ml vs. 102 (IQR 84, 123) ml, p = 0.019], a larger tenting height 10 (IQR 9, 13) mm vs. 8 (IQR 7, 11) mm (p = 0.047), and a larger mitral valve annulus [41 (IQR 38, 43) mm vs. 39 (IQR 36, 40) mm, p = 0.015] when compared to patients with durable optimal long-term results. In a multivariate regression model, the left ventricular sphericity index [Odds Ratio (OR) 1.120, 95% Confidence Interval (CI) 1.039-1.413, p = 0.003)], tenting height (OR 1.207, 95% CI 1.031-1.413, p = 0.019), and left atrium enlargement (OR 1.018, 95% CI 1.000-1.038, p = 0.047) were predictors for MR recurrence after 1 year. In patients with FMR, baseline parameters of advanced heart failure such as spherical ventricle, tenting height and a large left atrium might indicate risk of recurrent MR one year after PMVR.

The analysis of left ventricular ejection fraction after minimally invasive surgery for primary mitral valve regurgitation.

BACKGROUND: Although minimally invasive mitral valve surgery (MIMVS) has become the first choice for primary mitral regurgitation (MR) in recent years, clinical evidence in this field is yet limited. The main focus of this study was the analysis of preoperative (Pre), postoperative (Post), and 1-year follow-up (Fu) data in our series of MIMVS to identify factors that have an impact on the left ventricular ejection fraction (LVEF) evolution after MIMVS. METHODS: We reviewed the perioperative and 1-year follow-up data from 436 patients with primary MR (338 isolated MIMVS und 98 MIMVS combined with tricuspid valve repair) to analyze patients' baseline characteristics, the change of LV size, the postoperative evolution of LVEF and its factors, and the clinical outcomes. RESULTS: The overall mean value of ejection fraction (EF) slightly decreased at 1-year follow-up (mean change of LVEF: -2.63 ± 9.00%). A significant correlation was observed for preoperative EF (PreEF) und EF evolution, the higher PreEF the more pronounced decreased EF evolution (in all 436 patients; r = -.54, p < .001, in isolated MIMVS; r = -.54, p < .001, in combined MIMVS; r = -.53, p < .001). Statistically significant differences for negative EF evolution were evident in patients with mild or greater tricuspid valve regurgitation (TR) (in all patients; p < .05, odds ratio [OR] = 1.64, in isolated MIMVS; p < .01, OR = 1.93, respectively). Overall clinical outcome in New York Heart Association classification at 1 year was remarkably improved. CONCLUSIONS: Our results suggest an excellent clinical outcome at 1 year, although mean LVEF slightly declined over time. TR could be a predictor of worsened follow-up LVEF in patients undergoing MIMVS.

Crosstalk of Diabetic Conditions with Static Versus Dynamic Flow Environment-Impact on Aortic Valve Remodeling.

Type 2 diabetes mellitus (T2D) is one of the prominent risk factors for the development and progression of calcific aortic valve disease. Nevertheless, little is known about molecular mechanisms of how T2D affects aortic valve (AV) remodeling. In this study, the influence of hyperinsulinemia and hyperglycemia on degenerative processes in valvular tissue is analyzed in intact AV exposed to an either static or dynamic 3D environment, respectively. The complex native dynamic environment of AV is simulated using a software-governed bioreactor system with controlled pulsatile flow. Dynamic cultivation resulted in significantly stronger fibrosis in AV tissue compared to static cultivation, while hyperinsulinemia and hyperglycemia had no impact on fibrosis. The expression of key differentiation markers and proteoglycans were altered by diabetic conditions in an environment-dependent manner. Furthermore, hyperinsulinemia and hyperglycemia affect insulin-signaling pathways. Western blot analysis showed increased phosphorylation level of protein kinase B (AKT) after acute insulin stimulation, which was lost in AV under hyperinsulinemia, indicating acquired insulin resistance of the AV tissue in response to elevated insulin levels. These data underline a complex interplay of diabetic conditions on one hand and biomechanical 3D environment on the other hand that possesses an impact on AV tissue remodeling.

Impella Support for Acute Myocardial Infarction Complicated by Cardiogenic Shock.

BACKGROUND: Percutaneous mechanical circulatory support devices are increasingly used in acute myocardial infarction complicated by cardiogenic shock (AMI-CS), despite limited evidence for their effectiveness. The aim of this study was to evaluate outcomes associated with use of the Impella device compared with intra-aortic balloon pump (IABP) and medical treatment in patients with AMI-CS. METHODS: Data of patients with AMI-CS treated with the Impella device at European tertiary care hospitals were collected retrospectively. All patients underwent early revascularization and received optimal medical treatment. Using IABP-SHOCK II (Intraaortic Balloon Pump in Cardiogenic Shock II) trial inclusion and exclusion criteria, 372 patients were identified and included in this analysis. These patients were matched to 600 patients from the IABP-SHOCK II trial. The following baseline criteria were used as matching parameters: age, sex, mechanical ventilation, ejection fraction, prior cardiopulmonary resuscitation, and lactate. Primary end point was 30-day all-cause mortality. RESULTS: In total, 237 patients treated with an Impella could be matched to 237 patients from the IABP-SHOCK II trial. Baseline parameters were similarly distributed after matching. There was no significant difference in 30-day all-cause mortality (48.5% versus 46.4%, P=0.64). Severe or life-threatening bleeding (8.5% versus 3.0%, P<0.01) and peripheral vascular complications (9.8% versus 3.8%, P=0.01) occurred significantly more often in the Impella group. Limiting the analysis to IABP-treated patients as a control group did not change the results. CONCLUSIONS: In this retrospective analysis of patients with AMI-CS, the use of an Impella device was not associated with lower 30-day mortality compared with matched patients from the IABP-SHOCK II trial treated with an IABP or medical therapy. To further evaluate this, a large randomized trial is warranted to determine the effect of the Impella device on outcome in patients with AMI-CS. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03313687.

Impact of spliceosome mutations on RNA splicing in myelodysplasia: dysregulated genes/pathways and clinical associations.

SF3B1, SRSF2, and U2AF1 are the most frequently mutated splicing factor genes in the myelodysplastic syndromes (MDS). We have performed a comprehensive and systematic analysis to determine the effect of these commonly mutated splicing factors on pre-mRNA splicing in the bone marrow stem/progenitor cells and in the erythroid and myeloid precursors in splicing factor mutant MDS. Using RNA-seq, we determined the aberrantly spliced genes and dysregulated pathways in CD34+ cells of 84 patients with MDS. Splicing factor mutations result in different alterations in splicing and largely affect different genes, but these converge in common dysregulated pathways and cellular processes, focused on RNA splicing, protein synthesis, and mitochondrial dysfunction, suggesting common mechanisms of action in MDS. Many of these dysregulated pathways and cellular processes can be linked to the known disease pathophysiology associated with splicing factor mutations in MDS, whereas several others have not been previously associated with MDS, such as sirtuin signaling. We identified aberrantly spliced events associated with clinical variables, and isoforms that independently predict survival in MDS and implicate dysregulation of focal adhesion and extracellular exosomes as drivers of poor survival. Aberrantly spliced genes and dysregulated pathways were identified in the MDS-affected lineages in splicing factor mutant MDS. Functional studies demonstrated that knockdown of the mitosis regulators SEPT2 and AKAP8, aberrantly spliced target genes of SF3B1 and SRSF2 mutations, respectively, led to impaired erythroid cell growth and differentiation. This study illuminates the effect of the common spliceosome mutations on the MDS phenotype and provides novel insights into disease pathophysiology.

In vivo lipid 'tag and track' approach shows acyl editing of plastid lipids and chloroplast import of phosphatidylglycerol precursors in Arabidopsis thaliana.

In plant lipid metabolism, the synthesis of many intermediates or end products often appears overdetermined with multiple synthesis pathways acting in parallel. Lipid metabolism is also dynamic with interorganelle transport, turnover, and remodeling of lipids. To explore this complexity in vivo, we developed an in vivo lipid 'tag and track' method. Essentially, we probed the lipid metabolism in Arabidopsis thaliana by expressing a coding sequence for a fatty acid desaturase from Physcomitrella patens (Δ6D). This enzyme places a double bond after the 6th carbon from the carboxyl end of an acyl group attached to phosphatidylcholine at its sn-2 glyceryl position providing a subtle, but easily trackable modification of the glycerolipid. Phosphatidylcholine is a central intermediate in plant lipid metabolism as it is modified and converted to precursors for other lipids throughout the plant cell. Taking advantage of the exclusive location of Δ6D in the endoplasmic reticulum (ER) and its known substrate specificity for one of the two acyl groups on phosphatidylcholine, we were able to 'tag and track' the distribution of lipids within multiple compartments and their remodeling in transgenic lines of different genetic backgrounds. Key findings were the presence of ER-derived precursors in plastid phosphatidylglycerol and prevalent acyl editing of thylakoid lipids derived from multiple pathways. We expect that this 'tag and track' method will serve as a tool to address several unresolved aspects of plant lipid metabolism, such as the nature and interaction of different subcellular glycerolipid pools during plant development or in response to adverse conditions.

Prognostic value of impaired hepato-renal function assessed by the MELD-XI score in patients undergoing percutaneous mitral valve repair.

OBJECTIVES: The objective of this study was to assess the prognostic value of the Model for End-stage Liver Disease (MELD)-XI score in patients undergoing PMVR with the MitraClip system. BACKGROUND: MELD-XI score, which was originally developed for prognostic assessment in patients with advanced liver disease, has been reported as a predictor of outcome in heart failure patients. METHODS: A total of 192 consecutive patients undergoing percutaneous mitral valve repair (PMVR) were included into final analysis. MELD-XI score was calculated on the day of the procedure and patients were categorized into three groups based on MELD-XI score and compared with regards to clinical characteristics and outcomes following PMVR. RESULTS: MELD-XI > 12 was associated with male gender, higher logistic EuroSCORE, reduced left ventricular ejection fraction, enlarged right ventricular end-diastolic diameter, degree of mitral regurgitation, increased NT-proBNP serum levels and elevated right atrial pressures. Youden-Index revealed a cutoff of 16 in the MELD-XI score as best predictor of one-year all-cause mortality. Kaplan-Meier analysis and the log-rank test confirmed increased one-year mortality in patients with critically high score above 16 (mortality MELD-XI score > 16 vs 16-12 vs <12:39% vs 9%. vs 15%; P = 0.005). Compared to patients with lower MELD-XI score, these patients exhibited a more than 3-fold increased one-year mortality after PMVR. CONCLUSION: Given the high mortality in patients with a MELD-XI score > 16, these patients require a high-risk preoperative assessment and should undergo a careful discussion within the heart team for the best treatment option given the considerable one-year mortality following PMVR.

Reduction of sleep-disordered breathing following effective percutaneous mitral valve repair with the MitraClip system.

PURPOSE: This study tested the hypothesis that a reduction of pulmonary congestion achieved by a reduction of mitral regurgitation (MR) severity in heart failure (HF) patients is associated with reduced event lengths of sleep-disordered breathing (SDB). METHODS: We prospectively enrolled 20 consecutive HF patients who underwent MitraClip implantation. Patients underwent cardiorespiratory polygraphic recording prior to and after percutaneous mitral valve repair (PMVR). Beyond routinely established indicators of apneas and hypopneas per hour (respiratory event index), we manually analyzed apnea event lengths. RESULTS: MitraClip implantation led to marked reduction of MR severity and a reduction in left atrial pressure. These hemodynamic changes were accompanied by changes in SDB: the subtype of SDB switched from CSA to OSA in 4 patients. Likewise, quantitative indicators of SDB were altered in both forms of SDB with a reduction in circulatory delay (CSA 38 ± 14 vs. 33 ± 15 s.; p = 0.002 and OSA 34 ± 9 vs. 28 ± 6 s.; p = 0.02) and a corresponding reduction in ventilation lengths in CSA patients (42 ± 15 vs. 37 ± 13 s.; p = 0.05). CONCLUSION: A reduction of pulmonary congestion as achieved by a decrease of left atrial pressure through successful MitraClip implantation is associated with a reduction in respiratory event lengths, further pointing towards a relation between SDB and HF.

Identification of bottlenecks in the accumulation of cyclic fatty acids in camelina seed oil.

Modified fatty acids (mFA) have diverse uses; for example, cyclopropane fatty acids (CPA) are feedstocks for producing coatings, lubricants, plastics and cosmetics. The expression of mFA-producing enzymes in crop and model plants generally results in lower levels of mFA accumulation than in their natural-occurring source plants. Thus, to further our understanding of metabolic bottlenecks that limit mFA accumulation, we generated transgenic Camelina sativa lines co-expressing Escherichia coli cyclopropane synthase (EcCPS) and Sterculia foetida lysophosphatidic acid acyltransferase (SfLPAT). In contrast to transgenic CPA-accumulating Arabidopsis, CPA accumulation in camelina caused only minor changes in seed weight, germination rate, oil accumulation and seedling development. CPA accumulated to much higher levels in membrane than storage lipids, comprising more than 60% of total fatty acid in both phosphatidylcholine (PC) and phosphatidylethanolamine (PE) versus 26% in diacylglycerol (DAG) and 12% in triacylglycerol (TAG) indicating bottlenecks in the transfer of CPA from PC to DAG and from DAG to TAG. Upon co-expression of SfLPAT with EcCPS, di-CPA-PC increased by ~50% relative to lines expressing EcCPS alone with the di-CPA-PC primarily observed in the embryonic axis and mono-CPA-PC primarily in cotyledon tissue. EcCPS-SfLPAT lines revealed a redistribution of CPA from the sn-1 to sn-2 positions within PC and PE that was associated with a doubling of CPA accumulation in both DAG and TAG. The identification of metabolic bottlenecks in acyl transfer between site of synthesis (phospholipids) and deposition in storage oils (TAGs) lays the foundation for the optimizing CPA accumulation through directed engineering of oil synthesis in target crops.