Correction to: A large-scale multiomics analysis of wheat stem solidness and the wheat stem sawfly feeding response, and syntenic associations in barley, Brachypodium, and rice.

The original version of this article contained a mistake. The word "RefSeq v.1" was incorrectly inserted on page 7. The correct sentence should be: To identify the differentially regulated transcripts, clean RNA-Seq reads were mapped onto the T. aestivum Chinese Spring chromosome 3B pseudomolecule.

A large-scale multiomics analysis of wheat stem solidness and the wheat stem sawfly feeding response, and syntenic associations in barley, Brachypodium, and rice.

The wheat stem sawfly (WSS), Cephus cinctus Norton (Hymenoptera: Cephidae), is an important pest of wheat and other cereals, threatening the quality and quantity of grain production. WSS larvae feed and develop inside the stem where they are protected from the external environment; therefore, pest management strategies primarily rely on host plant resistance. A major locus on the long arm of wheat chromosome 3B underlies most of the variation in stem solidness; however, the impact of stem solidness on WSS feeding has not been completely characterized. Here, we used a multiomics approach to examine the response to WSS in both solid- and semi-solid-stemmed wheat varieties. The combined transcriptomic, proteomic, and metabolomic data revealed that two important molecular pathways, phenylpropanoid and phosphate pentose, are involved in plant defense against WSS. We also detected a general downregulation of several key defense transcripts, including those encoding secondary metabolites such as DIMBOA, tricetin, and lignin, which suggested that the WSS larva might interfere with plant defense. We comparatively analyzed the stem solidness genomic region known to be associated with WSS tolerance in wild emmer, durum, and bread wheats, and described syntenic regions in the close relatives barley, Brachypodium, and rice. Additionally, microRNAs identified from the same genomic region revealed potential regulatory pathways associated with the WSS response. We propose a model outlining the molecular responses of the WSS-wheat interactions. These findings provide insight into the link between stem solidness and WSS feeding at the molecular level.

Plant miRNAs: biogenesis, organization and origins.

MicroRNAs, or miRNAs, are posttranscriptional regulators of gene expression. A wealth of observations and findings suggest highly complex, multicomponent, and intermingled pathways governing miRNA biogenesis and miRNA-mediated gene silencing. Plant miRNA genes are usually found as individual entities scattered around the intergenic and-to a much lesser extent-intragenic space, while miRNA gene clusters, formed by tandem or segmental duplications, also exist in plant genomes. Genome duplications are proposed to contribute to miRNA family expansions, as well. Evolutionarily young miRNAs retaining extensive homology to their loci of origin deliver important clues into miRNA origins and evolution. Additionally, imprecisely processed miRNAs evidence noncanonical routes of biogenesis, which may affect miRNA expression levels or targeting capabilities. Majority of the knowledge regarding miRNAs comes from model plant species. As ongoing research progressively expands into nonmodel systems, our understanding of miRNAs and miRNA-related pathways changes which opens up new perspectives and frontiers in miRNA research.

Neurochemical evaluation of brain function with 1H magnetic resonance spectroscopy in patients with fragile X syndrome.

Fragile X syndrome (FXS) is the most common hereditary disorder of intellectual disability. Cognitive deficits involve executive function, attention, learning and memory. Advanced neuroimaging techniques are available, and (1)H magnetic resonance spectroscopy (MRS) can be used as a complementary method to MR imaging to understand disease processes in brain, by in vivo demonstration of brain metabolites. MRS was performed in 13 male patients with FXS full mutation, and 13 age- and sex-matched healthy controls. FXS diagnosis was based on clinical evaluation, followed by detection of FMR1 full mutation. Axial T2 TSE, sagittal T1 SE and coronal 3D MPRAGE images were obtained for both morphological imaging and voxel localization. Following evaluation of conventional images, multivoxel MRS (CSI) through supraventricular white matter and single voxel MRS (svs) with an intermediate echo time (TE:135 ms) from the cerebellar vermis were performed. Choline/Creatine (Cho/Cr), N-acetyl aspartate/Creatine (NAA/Cr), and Choline/N-acetyl aspartate (Cho/NAA) ratios were examined at right frontal (RF), left frontal (LF), right parietal (RP), left parietal (LP), and cerebellar vermian (C) white matter. Statistical analyses were done using t-test and Mann-Whitney U tests. A statistically significant difference was observed in RP Cho/NAA ratio (cell membrane marker/neuroaxonal marker), FXS patients having lower levels than controls (P = 0.016). The results should be evaluated cautiously in parallel to consequences in brain metabolism leading to alterations in neurotransmitter levels, osmoregulation, energy metabolism and oxidative stress response described in animal models. MRS may serve to define a metabolic signature and biomarkers associated with FXS.

Phenotype properties and status of corticosteroid resistance among patients with uncontrolled asthma

Background: Control cannot be achieved in some asthmatics although optimal monitoring and treatment is administered. Glucocorticoid (GC) resistance is one of the reasons of poor asthma control. We aimed to investigate GC resistance by lymphocyte proliferation suppression test (LPST) in uncontrolled asthmatics. Methods: After assessing asthma control level of 77 asthmatics their treatment was adjusted upon GINA guidelines. They were followed-up for three to six months and the patients who remained uncontrolled were accepted as uncontrolled patients. Steroid resistance test (SRT) was applied to them (7–14 days oral prednisolone) and the patients who were still uncontrolled and/or had a FEV1 increase <15% after SRT were assessed as the “case group” while the remaining composed the “control group”. Optimal treatment was adjusted and at the end of a follow-up period LPST was performed to both groups. Results: Fourteen of the case (n = 22) and four (n = 8) of the control groups could be evaluated by LPST. Proliferated lymphocytes were observed to be significantly suppressed in all dexamethasone concentrations in the control group (p = 0.001). However, in the case group LPST was positive only at 10−6 and 10−4 concentrations although statistically not significant (p = 0.147). There was no significant relationship between clinically GC resistance and LPST positivity (p = 0.405). Conclusion: We determined that in vitro responses to the GCs were significantly declined in the uncontrolled asthma cases. An SRT alone does not seem to be very sensitive for evaluating GC sensitivity, LPST may be performed for demonstrating GC responsiveness in asthmatic patients in addition to SRT (AU)

5-Fluorouracil signaling through a calcium-calmodulin-dependent pathway is required for p53 activation and apoptosis in colon carcinoma cells.

5-Fluorouracil (5-FU) is an anti-metabolite that is in clinical use for treatment of several cancers. In cells, it is converted into three distinct fluoro-based nucleotide analogs, which interfere with DNA synthesis and repair, leading to genome impairment and, eventually, apoptotic cell death. Current knowledge states that in certain cell types, 5-FU-induced stress is signaling through a p53-dependent induction of tumor necrosis factor-receptor oligomerization required for death-inducing signaling complex formation and caspase-8 activation. Here we establish a role of calcium (Ca(2+)) as a messenger for p53 activation in response to 5-FU. Using a combination of pharmacological and genetic approaches, we show that treatment of colon carcinoma cells stimulates entry of extracellular Ca(2+) through long lasting-type plasma membrane channels, which further directs posttranslational phosphorylation of at least three p53 serine residues (S15, S33 and S37) by means of calmodulin (CaM) activity. Obstructing this pathway by the Ca(2+)-chelator BAPTA (1,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid) or by inhibitors of CaM efficiently reduces 5-FU-induced caspase activities and subsequent cell death. Moreover, ectopic expression of p53 S15A in HCT116 p53(-/-) cells confirmed the importance of a Ca(2+)-CaM-p53 axis in 5-FU-induced extrinsic apoptosis. The fact that a widely used therapeutic drug, such as 5-FU, is operating via this pathway could provide new therapeutic intervention points, or specify new combinatorial treatment regimes.

Phenotype properties and status of corticosteroid resistance among patients with uncontrolled asthma.

BACKGROUND: Control cannot be achieved in some asthmatics although optimal monitoring and treatment is administered. Glucocorticoid (GC) resistance is one of the reasons of poor asthma control. We aimed to investigate GC resistance by lymphocyte proliferation suppression test (LPST) in uncontrolled asthmatics. METHODS: After assessing asthma control level of 77 asthmatics their treatment was adjusted upon GINA guidelines. They were followed-up for three to six months and the patients who remained uncontrolled were accepted as uncontrolled patients. Steroid resistance test (SRT) was applied to them (7-14 days oral prednisolone) and the patients who were still uncontrolled and/or had a FEV1 increase <15% after SRT were assessed as the "case group" while the remaining composed the "control group". Optimal treatment was adjusted and at the end of a follow-up period LPST was performed to both groups. RESULTS: Fourteen of the case (n=22) and four (n=8) of the control groups could be evaluated by LPST. Proliferated lymphocytes were observed to be significantly suppressed in all dexamethasone concentrations in the control group (p=0.001). However, in the case group LPST was positive only at 10(-6) and 10(-4) concentrations although statistically not significant (p=0.147). There was no significant relationship between clinically GC resistance and LPST positivity (p=0.405). CONCLUSION: We determined that in vitro responses to the GCs were significantly declined in the uncontrolled asthma cases. An SRT alone does not seem to be very sensitive for evaluating GC sensitivity, LPST may be performed for demonstrating GC responsiveness in asthmatic patients in addition to SRT.

11ß-hydroxysteroid dehydrogenase type 1 gene expression is increased in ascending aorta tissue of metabolic syndrome patients with coronary artery disease.

11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD-1) activity and mRNA levels are increased in visceral and subcutaneous adipose tissues of metabolic syndrome subjects. We analyzed 11ß-HSD-1 expression in human epicardial adipose (EA) and ascending aorta (AA) tissues of metabolic syndrome patients and examined their contribution to the development of coronary atherosclerosis. The 11ß-HSD-1 expression was evaluated by qRT-PCR in EA and AA tissues of 20 metabolic syndrome patients with coronary artery disease (metabolic syndrome group) and 10 non-metabolic syndrome patients without coronary artery disease (controls). 11ß-HSD-1 expression was increased in EA and AA tissues of the metabolic syndrome group (4.1- and 5.5-fold, respectively). A significant positive correlation was found between 11ß-HSD-1 expression in EA tissue and waist hip ratio and 11ß-HSD-1 expression in AA tissue and body mass index, while a negative correlation was found between 11ß-HSD-1 expression in EA tissue and HDL. Expression of CD68, a macrophage marker, was significantly increased in both tissues of the metabolic syndrome group; it was 2-fold higher in AA tissue compared to EA tissue in the metabolic syndrome group. Our findings of increased expression of 11ß-HSD-1 and CD68 in AA tissue of the metabolic syndrome group lead us to suggest that they contribute to coronary atherosclerosis in metabolic syndrome. This positive correlation between obesity markers and 11ß-HSD-1 in AA and EA tissues strengthens the evidence that 11ß-HSD-1 has a role in metabolic syndrome. To the best of our knowledge, this is the first report showing 11ß-HSD-1 and CD68 expression in AA tissue of metabolic syndrome patients. We suggest that there is tissue-specific expression of 11ß-HSD-1 in metabolic syndrome and associated cardiovascular disorders.

Plant abiotic stress signaling.

Stress signaling is central to plants which--as immobile organisms--have to endure environmental fluctuations that constantly interfere with vigorous growth. As a result, plant-specific, elaborate mechanisms have evolved to perceive and respond to stress conditions. Currently, these stress responses are plausibly being revealed to involve crosstalks with energy signaling pathways as any growth-limiting factor alters plant's energy status. Among these, autophagy, conventionally regarded as the mechanism whereby plants recycle and remobilize nutrients in bulk, has frequently been associated with stress responses. With the recent discoveries, however, autophagy has attained a novel role in stress signaling. In this review, major elements of abitoic stress signaling are summarized along with autophagy pathway, and in the light of recent discoveries, a putative, state-of-art role of autophagy is discussed.

Does off-pump coronary artery bypass surgery reduce mortality in high risk patients?

BACKGROUND: The aim of this retrospective study was to compare outcome in two groups of patients who were classified according to their risk groups and underwent coronary revascularization with or without cardiopulmonary bypass. MATERIAL AND METHODS: Between January 1996 and July 2000, 480 cases that underwent coronary artery bypass surgery (CABG) were included in a retrospective nonrandomized manner for study. Group 1 included 210 patients who were revascularized using off-pump techniques. Octopus 2 and 3 (Medtronic, Inc., Minneapolis, MN) were used for tissue stabilization. Group 2 included 270 cases who underwent CABG using CPB. Emergency cases, combined operations, reoperations, and patients in cardiogenic shock were excluded. Demographic variables were comparable between two the groups. Using the Allegheny Clinic Risk Scoring Scale [Magovern 1996], patients in both groups were scored as low, moderate, and high risk. In Group 1, 37 % of patients consisted of high risk patients while Group 2 had 14% (p < 0.05). Student's t-test and chi-square test were used for statistical analysis and alfa < 0.05 was considered significant. RESULTS: Mortality was 1.4% in Group 1 and 1.5% in Group 2 (p = ns). Mean anastomosis per patient was 2.6 +/- 0.6 in Group 1 and 3.2 +/- 0.5 in Group 2 (p < 0.05). Patients in Group 1 needed less blood transfusions and less inotropic support postoperatively (p < 0.05). There were also fewer minor neurological events (p < 0.05) and pulmonary complications (Type 2) in Group 1. Atrial fibrillation rate, infection, and major neurological deficit (Type 1) were similar in both groups. Mortality was less among Group 1 high risk patients (3.9 %) in comparison to Group 2 high risk patients (7.9 %), but this did not reach statistical significance. CONCLUSIONS: In low or moderate risk patients, CABG can be performed safely with or without CPB. In high risk patients with several comorbidities, off-pump CABG seems to be a safe and efficient method that can improve outcome.

The use of the 5-HT3-receptor antagonist ondansetron for the treatment of postcardiotomy delirium.

OBJECTIVE: To evaluate the effect of the 5-HT3-receptor antagonist ondansetron in patients with postcardiotomy delirium. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Thirty-five patients who had undergone coronary artery bypass graft surgery. INTERVENTIONS: Thirty-five patients, 23 men and 12 women, who developed delirium in the intensive care unit after coronary artery bypass graft surgery were included. Mean patient age was 51.3 years (range, 36 to 79 years). A mental status scoring scale was developed, and patients were scored 0 to 4 according to their delirium status after confirming that there were no correctable metabolic abnormalities as an underlying cause for delirium. Normal behavior was scored as 0, and severe verbal and physical agitation was scored as 4. Patients received a single dose of ondansetron, 8 mg, intravenously and were reevaluated 10 minutes later. MEASUREMENTS AND MAIN RESULTS: Before the treatment, 7 patients had a score of 2 (20%); 10 patients (28.6%), 3; and 18 patients (51.4%), 4. After the treatment, 28 patients (80%) dropped their score to 0; 6 patients (17.1%) dropped to a score of 1, and 1 patient (2.9%) remained at a score of 4. The mean score dropped from 3.20 + 1.01 to 0.29 + 0.75 after treatment. Wilcoxon signed ranks test was used for statistical evaluation, and the fall in delirium score after ondansetron treatment was found to be statistically significant (p < 0.001). CONCLUSIONS: The use of ondansetron was effective and safe and without important side effects. This positive effect of the 5-HT3-receptor antagonist ondansetron led to speculation that impaired serotonin metabolism may play a role in postcardiotomy delirium.

The hazardous effects of alveolar hypocapnia on lung mechanics during weaning from cardiopulmonary bypass.

The bronchoconstrictive effects of alveolar hypocapnia during weaning from cardiopulmonary bypass (CPB) were investigated in patients undergoing elective coronary artery revascularization. Thirty patients were randomly assigned into two equal groups. In both groups, mechanical ventilation was initiated for 3 min prior to weaning from CPB with the venous pressure low. This kept the pulmonary vascular bed empty, resulting in alveolar hypocapnia (ETCO2 < 2 kPa). Peak airway pressure (P(peak)) and plateau pressures (P(plateau)) were recorded. In group 1, 5% CO2 was added to the inspiratory gas mixture and the ETCO2 allowed to rise (ETCO2 > 3.3 kPa). The ventilation pressure measurements were recorded again after 3 min stabilization. In group 2, the venous pressure was increased to allow the pulmonary venous bed to fill and the ventilation pressures recorded after a 3 min period of stabilization. In group 1, the ventilatory pressures dropped significantly (p < 0.001) when the alveolar hypocapnia was reversed with added CO2 (P(peak) 19.71 +/- 5.7 to 12.31 +/- 2.8 cmH2O and P(plateau) 13.15 +/- 3.28 to 9.15 +/- 2.23 cmH2O). In group 2, a similar effect was achieved by allowing filling of the pulmonary vascular bed (P(peak) 17.46 +/- 4.72 to 11.92 +/- 3.03 cmH2O and P(plateau) 13.93 +/- 4.10 to 9.37 +/- 3.00 cmH2O). These results suggest that filling the pulmonary vascular bed prior to initiating ventilation, when weaning from CPB, prevents the otherwise deleterious effects of alveolar hypocapnia, resulting in raised bronchomotor tonus and raised airway pressures.

Off-pump coronary artery bypass grafting with use of the octopus 2 stabilization system.

BACKGROUND: The treatment of coronary artery disease has evolved rapidly over the last two decades. The gold standard of surgical revascularization, the on-pump coronary artery bypass graft, has been challenged by the development of percutaneous transluminal coronary angioplasty. Our experience with the alternative of the off-pump ("beating heart") coronary artery bypass (OPCAB) technique during a period of 18 months suggests that OPCAB avoids the complications of cardiopulmonary bypass and offers patients the benefit of long-term graft patency that greatly exceeds that of current endovascular technologies. METHODS: The early results of 126 OPCAB procedures performed through a medial sternotomy incision during a period of 18 months were evaluated. There were 80 male and 46 female patients, with a mean age of 69 +/- 4.3 years. Emergency cases and reoperations were not included. A total of 268 anastomoses were performed, with a mean number of 2.12 anastomoses per patient. Conduits used, with their percentage of use, were: left internal thoracic artery (LITA) (100%), right internal thoracic artery (11.1%), greater saphenous vein (84%), and radial artery (31%). In 72% of the cases, off-pump surgery was chosen because of patient risk factors such as atherosclerotic aortic disease, previous cerebrovascular accident or carotid artery disease, renal dysfunction, malignancy or poor left ventricular function. RESULTS: There was no operative mortality. One-month postoperative mortality was three patients (2.3%). Two died because of mesenteric ischemia, and the other death was due to cardiac failure. Seventy-one patients had a control angiogram before discharge. The patency of LITA anastomosis was 100% while overall patency rate was 95%. In 43 patients for whom an angiogram could not be performed, a Thallum 201 stress test was performed three months postoperatively. Thirty-eight patients had a normal test while five patients showed signs of ischemia. These patients had a control angiogram: in four patients anastomoses were patent, but in one patient there was a severe narrowing of a venous anastomosis to the distal right coronary artery (RCA) which was corrected with angioplasty. In the whole series eight patients (6.3%) refused to have any control examination. CONCLUSIONS: Our early results suggest that off-pump CABG with Octopus 2 (Medtronic, Inc., Minneapolis, MN) can be a good alternative in high risk patients who need multiple vessel revascularization.

The use of a stentless porcine bioprosthesis to repair an ascending aortic aneurysm in combination with aortic valve regurgitation.

Over the years, many surgical methods have evolved for the treatment of ascending aortic aneurysm in combination with aortic valve regurgitation; however, precise guidelines for optimal surgical techniques for varying presentations have not been defined. We describe the use of a stentless porcine bioprosthesis (Medtronic Freestyle) in a patient with an ascending aortic aneurysm and aortic regurgitation. We used the complete root replacement method, and anastomosed a Dacron graft (Hemashield) between the bioprosthetic valve and the native aorta to replace the distal part of the aneurysm.

A no-touch technique for calcified ascending aorta during coronary artery surgery.

Despite improvements in cardiovascular surgery techniques over the years, the incidence of neurologic complications has not declined, and stroke remains a possible (and devastating) sequela to coronary artery surgery. In this report, we describe a moderate hypothermic fibrillatory arrest technique that avoids cross-clamping or otherwise touching the aorta; use of the internal thoracic arteries and the right gastroepiploic artery provides optimum revascularization and minimizes the risk of cerebrovascular accident. Over a 1-year period, we used the technique in 21 patients who had heavy calcifications of the ascending aorta. No hemodynamic problems, lower-limb ischemia, or neurologic complications were seen. Only 1 patient underwent reoperation (for bleeding), and another--whose revascularization was incomplete--had a high postoperative level of myocardial creatine kinase MB isoenzyme and a new Q wave, but no hemodynamic deterioration. This technique seems reasonable, because it appears to provide good myocardial protection and to reduce neurologic complications, without comprising myocardial revascularization.