Agronomic performance of two generations (F12 and F13) of thirteen winter wheat composite cross wheat populations with differing cultivation histories in 2014/15.

As environmental and agronomic conditions are heterogeneous between and within locations, diversity within varieties or crop populations should increase adaptability to the changing and variable range of growing environments. The additional pressure of plant genetic diversity loss, has driven novel breeding approaches such as Composite Cross Populations (CCPs) and other genotype mixtures, thereby increasing both intra- and inter-varietal diversity and ensuring a “wider adaptation” capacity for crop varieties (Döring et al., 2011). A winter wheat (Triticum aestivum L.) CCP was created by intercrossing 20 varieties in 2001, through collaboration with the Elm Farm Research Centre and the John Innes Institute. In 2005, a seed batch of the F4 was equally divided and distributed to Hungary and Germany. In 2007, it was decided to submit one of the CCPs to changes in environments every year. A pattern was developed between eight partners whereby these “cycling” populations would be grown in a plot of >100m2 and sent to the next cycling partner the following year. The aim of the project was to compare a total of 13 populations that all originated from the same seed batch in 2005, but that have been exposed to vastly different climatic conditions over time, in one site (Germany). In 2014/15, the second experimental year, saved seed from 2013 (F12) and harvested seed from 2014 (F13) were sown, in order to compare two generations in one growing season. The experimental year 2014/15 was characterized by long dry periods, particularly between February and June 2015, and under these dry conditions most populations outyielded the selected reference varieties. There was no effect of differential seed size of the two generations for most agronomic characteristics for each population. Although the harvested TGW of both the F12 and the F13 of each population was not significantly different from one another, there were still significant differences of harvested TGW between the populations in the F12. These significant differences of harvested TGW were no longer present in the F13 between each population after one year under the same management system. These results indicate that the heritability of seed size is low as has been shown before (Silvertown, 1989) and that seed size variation tends to be a result of phenotypic plasticity, which is thought to be adaptive, especially as the result of environmental variation (Marshall et al., 1985; Vaughton and Ramsey, 1998; Lehtilä and Ehrlén, 2005)

From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on "New frontiers in cardiovascular research"

In this meeting report, particularly addressing the topic of protection of the cardiovascular system from ischemia/reperfusion injury, highlights are presented that relate to conditioning strategies of the heart with respect to molecular mechanisms and outcome in patients' cohorts, the influence of co-morbidities and medications, as well as the contribution of innate immune reactions in cardioprotection. Moreover, developmental or systems biology approaches bear great potential in systematically uncovering unexpected components involved in ischemia-reperfusion injury or heart regeneration. Based on the characterization of particular platelet integrins, mitochondrial redox-linked proteins, or lipid-diol compounds in cardiovascular diseases, their targeting by newly developed theranostics and technologies opens new avenues for diagnosis and therapy of myocardial infarction to improve the patients' outcome

Cardiac surgery with crystalloid cardioplegia: Improved functional recovery due to molecular adaptations in adult rat hearts

Background: The effect of aging on functional recovery after a period of crystalloid cardioplegic arrest is still a matter of debate. We hypothesized that age-dependent differences in the polyamine metabolism may contribute to such differences. Methods: Hearts from juvenile and adult Wistar rats were placed in a perfused beating heart model and given Bretschneider's cardioplegia for an ischemia period of 60 min. During reperfusion, recovery of contractile function and coronary blood flow were measured for 90 min. In addition, adult hearts received putrescine to bypass polyamine metabolism during the 1st min of reperfusion. In comparison, the effect of putrescine was analyzed from hearts reperfused after 45-min flow arrest for 90 min. The rate-limiting enzyme of the polyamine metabolism, ornithine decarboxylase (ODC), the proapoptotic enzyme bax, and the relation between SR-calcium-ATPase (SERCA2a) and a natrium-calcium-exchanger enzyme were determined on mRNA-level through real-time polymerase chain reaction. Results: Adult hearts had lower basal performance and lower SERCA mRNA expression compared to juvenile hearts. However, after a 60-min aortic clamping period, recovery of left ventricular developed pressure (105.6 ± 39.7% of baseline) in the adult group was better than in the young group (61.3 ± 34.1% of baseline). ODC mRNA was significantly (P = 0.04228) lower in adult hearts (0.60 ± 0.09-fold vs. juvenile rats). Similar, bax mRNA was significantly (P = 0.01662) lower in adult hearts (0.22 ± 0.03-fold vs. juvenile rats). Addition of putrescine to adult hearts during reperfusion attenuated a better outcome of these hearts suggesting a detrimental effect of polyamine metabolism after cardioplegic arrest. In contrast, putrescine improved recovery in postischemic hearts without exposure to cardioplegic solution. Conclusion: Adult rat hearts tolerate cardioplegia-mitigated ischemia better than juvenile hearts because they express less ODC during resubstitution of normal calcium levels

Redox status of patients before cardiac surgery

Objectives: Redox regulation plays a crucial role in balancing the cardiovascular system. In this prospective study we aimed to identify currently unknown correlations valuable to cardiovascular research and patient management. Methods: Blood samples from 500 patients were collected directly before cardiosurgical interventions (Ethics Committee reference number 85/11). Four central redox parameters were determined together with about 30 clinical, anthropometric, and metabolic parameters. Results: Creatinine levels and pulmonary hypertension were significant predictors of the total antioxidant status (TAOS) in the patients; total glutathione levels were linked to C-peptide, and creatinine, gender, and ventricular arrhythmia influenced nitrate/nitrite levels. Notably, significant interactions were found between medication and redox parameters. Calcium channel blockers (CCBs) were positive predictors of total glutathione levels, whereas angiotensin-converting enzyme inhibitors and CCBs were negative predictors of NOx levels. Age showed the highest correlation with the duration of the intensive care stay, followed by NOx levels, creatinine, TAOS, and C-reactive protein. Discussion: In this prospective study we determined multiple correlations between redox markers and parameters linked to cardiovascular diseases. The data point towards so far unknown interdependencies, particularly between antihypertensive drugs and redox metabolism. A thorough follow-up to these data has the potential to improve patient management. Abbreviations: A: absorption; ΔA: absorption difference; ABTS: 2,2′-azino-di(3-ethylbenzothiazoline sulfonate); ACE: angiotensin-converting enzyme; AO: antioxidant; ARB: angiotensin receptor blocker; BMI: body mass index; CAD: coronary artery disease; CCB: calcium channel blocker; CDC: coronary heart diseases; COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; CVD: cardiovascular diseases; Cu-OOH: cumene hydroperoxide; D: dilution factor; DAN: 2,3-diaminonaphtalene; DMSO: dimethylsulfoxide; DNA: deoxyribonucleic acid; DTNB: 5,5-dithiobis(2-nitrobenzoate); ε: extinction coefficient; EDRF: endothelium-derived relaxing factor; fc: final concentration; GPx: glutathione peroxidases; (h)GR: (human) glutathione reductase; GSH: (reduced) glutathione; GSSG: glutathione disulfide; GST: glutathione-S-transferase; Hb: hemoglobin; HDL: high-density lipoprotein; Hk: hematocrit; H2O2: hydrogen peroxide; ICS: intensive care stay; LDH: lactate dehydrogenase; LDL: low-density lipoprotein; MI: myocardial infarction; NED: N-(1-naphthyl)-ethylendiamine-dihydrochloride; NOS: nitric oxide synthase; NOx: nitrate/nitrite; NR: nitrate reductase; PBS: phosphate buffered saline; PCA: principle component analysis; PH: pulmonary hypertension; ROS: reactive oxygen species; RNS: reactive nitrogen species; RT: room temperature (25°C); SA: sulfanilamide; SOD: superoxide dismutase; SSA: sulfosalicylic acid; TAC: total antioxidant capacity; TAOS: total antioxidant status; TEAC: trolox equivalent antioxidative capacity; TG: triglycerides; tGSH: total glutathione; TNB-: 2-nitro-5-thiobenzoate; U: unit; UV: ultraviolet; VA: volume activity; Wc: working concentration; WHR: waist-hip ratio

Differential Expression of MicroRNAs in Endarterectomy Specimens Taken from Patients with Asymptomatic and Symptomatic Carotid Plaques.

OBJECTIVE:Stroke and transient ischemic attacks are considered as clinical manifestations of atherosclerotic disease due to on-going vascular inflammation and finally atherothrombosis of the carotid arteries. MicroRNAs (miRNA/miR) are known to be involved in vascular inflammation and plaque destabilization. The aim of this study was to analyze the expression profile of selected miRNAs in endarterectomy specimen from carotid arteries that were taken from patients with asymptomatic and symptomatic atherosclerotic plaques. METHODS AND RESULTS:11 miRNAs were selected and their expression was analyzed using real-time RT-PCR. Therefore, samples were divided into three different groups. On the one hand we investigated the expression patterns from patients in asymptomatic (n = 14) and symptomatic (n = 10) plaques; on the other hand we took samples from normal configurated internal mammary arteries (n = 15). Out of these 11 targets we identified some miRNAs, which were up- or down-regulated in either one of the two groups. Interestingly, the expression of two miRNAs was significantly different between asymptomatic and symptomatic samples, namely miR-21 (P<0.01) and miR-143 (P<0.05). CONCLUSION:In the present study, we identified miRNA subtypes which showed different expression in endarterectomy specimen from patients with asymptomatic and symptomatic plaques, suggesting that these miRNAs correlated with advanced vascular inflammation and plaque stability. They may represent new therapeutic targets for vascular proliferative diseases such as atherosclerosis

Preoperative intra-aortic counterpulsation in high-risk patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials

In contrast to the results of previous studies, recent randomized controlled trials (RCTs) failed to show a benefit of prophylactic aortic counterpulsation in high-risk patients undergoing cardiac surgery. The present analysis aims to redefine the effects of this treatment modality in the light of this new evidence. MEDLINE, EMBASE, CENTRAL/CCTR, Google Scholar and reference lists of relevant articles were searched for full-text articles of RCTs in English or German. Assessments for eligibility, relevance, study validity and data extraction were performed by two reviewers independently using prespecified criteria. The primary outcome was hospital mortality. A total of nine eligible RCTs with 1171 patients were identified: 577 patients were treated preoperatively with intra-aortic balloon pump (IABP) and 594 patients served as controls. The pooled odds ratio (OR) for hospital mortality (22 hospital deaths in the intervention arm, 54 in the control group) was 0.381 (95% CI 0.230-0.629; P < 0.001). The pooled analyses of five RCTs including only patients undergoing isolated on-pump coronary artery bypass grafting (n[IABP] = 348, n[control] = 347) also showed a statistically significant improvement in mortality for preoperative IABP implantation (fixed-effects model: OR 0.267, 95% CI 0.129-0.552, P < 0.001). The pooled OR for hospital mortality from two randomized off-pump trials was 0.556 (fixed-effects model, 95% CI 0.207-1.493, P = 0.226). Preoperative aortic counterpulsation was associated with a significant reduction in low cardiac output syndrome (LCOS) in the total population (fixed-effects model: OR 0.330, 95% CI 0.214-0.508, P < 0.001) as well as in the subgroup of CAGB patients (fixed-effects model: OR 0.113, 95% CI 0.056-0.226, P < 0.001), whereas there was no benefit in the off-pump population (fixed-effects model: OR 0.555, 95% CI 0.209-1.474, P = 0.238). Preoperative IABP implantation was associated with a reduction of intensive care unit (ICU) stay in all investigated populations with a greater effect in the total population [fixed-effects model: standard mean difference (SMD) -0.931 +/- 0.198, P < 0.001] as well as in the subgroup of CAGB patients (fixedeffects model: SMD -1.240 +/- 0.156, P < 0.001), compared with the off-pump group (fixed-effects model: SMD -0.723 +/- 0.128, P < 0.001). Despite contradictory results from recent trials, the present study confirms the findings of previous meta-analyses that prophylactic aortic counterpulsation reduces hospital mortality, incidence of LCOS and ICU requirement in high-risk patients undergoing on-pump cardiac surgery. However, owing to small sample sizes and the lack of a clear-cut definition of high-risk patients, an adequately powered, prospective RCT is necessary to find a definite answer to the question, if certain groups of patients undergoing cardiac surgery benefit from a prophylactic IABP insertion

Minimized Extracorporeal Circulation Is Associated with Reduced Plasma Levels of Free-Circulating Mitochondrial DNA Compared to Conventional Cardiopulmonary Bypass: A Secondary Analysis of an Exploratory, Prospective, Interventional Study

The use of minimized extracorporeal circulation (MiECC) during cardiac surgery is associated with a reduced inflammatory reaction compared to conventional cardiopulmonary bypass (cCPB). Since it is unknown if MiECC also reduces the amount of free-circulating mitochondrial DNA (mtDNA), this study aims to compare MiECC-induced mtDNA release to that of cCPB as well as to identify potential relations between the plasma levels of mtDNA and an adverse outcome. Overall, 45 patients undergoing cardiac surgery with either cCPB or MiECC were included in the study. MtDNA encoding for NADH dehydrogenase 1 was quantified with quantitative polymerase chain reaction. The plasma amount of mtDNA was significantly lower in patients undergoing cardiac surgery with MiECC compared to cCPB (MiECC: 161.8 (65.5–501.9); cCPB 190.8 (82–705.7); p p 650 copies/µL after the commencement of CPB had a 5-fold higher risk for postoperative atrial fibrillation independently of the type of cardiopulmonary bypass. An amount of mtDNA being higher than 650 copies/µL showed moderate predictive power (AUROC 0.71 (0.53–071)) for the identification of postoperative atrial fibrillation. In conclusion, plasma levels of mtDNA were lower in patients undergoing cardiac surgery with MiECC compared to cCPB. The amount of mtDNA at the beginning of the CPB was associated with postoperative atrial fibrillation independent of the type of cardiopulmonary bypass

Flow Cytometry-Based Quantification of Neutrophil Extracellular Traps Shows an Association with Hypercoagulation in Septic Shock and Hypocoagulation in Postsurgical Systemic Inflammation—A Proof-of-Concept Study

This proof-of-concept study aimed to evaluate a novel method of flow cytometry-based quantification of neutrophil extracellular traps (NETs) in septic shock patients and to identify possible interactions between the number of free-circulating NETs and alterations of the coagulatory system. Patients suffering from septic shock, a matched control group (CTRL), and patients suffering from systemic inflammation after cardiac (CABG) or major abdominal surgery (MAS) were enrolled in this prospective proof-of-concept study. Compared to the matched controls, free-circulating NETs were significantly elevated in septic shock and postsurgical patients (data are presented in median (IQR)); septic shock: (2.7 (1.9&ndash;3.9); CABG: 2.7 (2.1&ndash;3.7); MAS: 2.7 (2.1&ndash;3.9); CTRL: 1.6 (1&ndash;2); CTRL vs. septic shock: p = 0.001; CTRL vs. CABG: p &lt; 0.001; CTRL vs. MAS: p &lt; 0.001). NETs correlated positively with FIBTEM mean clot firmness (MCF) in septic shock patients (r = 0.37, p &lt; 0.01) while they correlated negatively in surgical patients (CABG: r = &minus;0.28, p &lt; 0.01; MAS: r = &minus;0.25, p = 0.03). Flow-cytometric quantification of NETs showed a significant increase in free-circulating NETs under inflammatory conditions. Furthermore, this study hints to an association of the number of NETs with hypercoagulation in septic shock patients and hypocoagulation in surgery-induced inflammation