Proteomic analysis of proteins responsive to drought and low temperature stress in a hard red spring wheat cultivar

Drought stress is becoming more prevalent with global warming, and has been shown to have large effects on gluten proteins linked to wheat bread making quality. Likewise, low temperature stress can detrimentally affect proteins in wheat. This study was done to determine the differential abundance of high molecular weight (HMW) glutenin proteins in a drought and low temperature stressed high quality hard red spring wheat cultivar (PAN3478), against a control. The treatments were applied in the greenhouse at the soft dough stage. HMW glutenin proteins were extracted from the flour, and were separated by using two-dimensional gel electrophoresis. Protein spots that had p values lower than 0.05 and fold values equal to or greater than 1.2 were considered to be significantly differentially abundant. These proteins were further analyzed by using tandem mass spectrometry. There was a 1.3 to 1.8 fold change in 17 protein spots due to the cold treatment. The drought treatment caused a 1.3 to 3.8 fold change in 19 protein spots. These spots matched either HMW or low molecular weight (LMW) glutenin subunits. In the latter case, the C subunits of LMW glutenins were notably found to be up-regulated under both stress conditions. All the proteins that have been identified can directly influence dough characteristics. Data are available via ProteomeXchange with the identifier PXD017578

Non-Coding RNA and Tumor Development in Neurofibromatosis Type 1: ANRIL Rs2151280 Is Associated with Optic Glioma Development and a Mild Phenotype in Neurofibromatosis Type 1 Patients

Non-coding RNAs (ncRNAs) are known to regulate gene expression at the transcriptional and post-transcriptional levels, chromatin remodeling, and signal transduction. The identification of different species of ncRNAs, microRNAs (miRNAs), circular RNAs (circRNAs), and long ncRNAs (lncRNAs)-and in some cases, their combined regulatory function on specific target genes-may help to elucidate their role in biological processes. NcRNAs' deregulation has an impact on the impairment of physiological programs, driving cells in cancer development. We here carried out a review of literature concerning the implication of ncRNAs on tumor development in neurofibromatosis type 1 (NF1), an inherited tumor predisposition syndrome. A number of miRNAs and a lncRNA has been implicated in NF1-associated tumors, such as malignant peripheral nerve sheath tumors (MPNSTs) and astrocytoma, as well as in the pathognomonic neurofibromas. Some authors reported that the lncRNA ANRIL was deregulated in the blood of NF1 patients with plexiform neurofibromas (PNFs), even if its role should be further elucidated. We here provided original data concerning the association of a specific genotype about ANRIL rs2151280 with the presence of optic gliomas and a mild expression of the NF1 phenotype. We also detected the LOH of ANRIL in different tumors from NF1 patients, supporting the involvement of ANRIL in some NF1-associated tumors. Our results suggest that ANRIL rs2151280 may be a potential diagnostic and prognostic marker, addressing early diagnosis of optic glioma and predicting the phenotype severity in NF1 patients

Advances in Li-Ion battery management for electric vehicles

This paper aims at presenting new solutions for advanced Li-Ion battery management to meet the performance, cost and safety requirements of automotive applications. Emphasis is given to monitoring and controlling the battery temperature, a parameter which dramatically affects the performance, lifetime, and safety of Li-Ion batteries. In addition to this, an innovative battery management architecture is introduced to facilitate the development and integration of advanced battery control algorithms. It exploits the concept of smart cells combined with an FPGA-based centralized unit. The effectiveness of the proposed solutions is shown through hardware-in-the-loop simulations and experimental results

VDAC3 as a sensor of oxidative state of the intermembrane space of mitochondria: the putative role of cysteine residue modifications

Voltage-Dependent Anion selective Channels (VDAC) are pore-forming mitochondrial outer membrane proteins. In mammals VDAC3, the least characterized isoform, presents a set of cysteines predicted to be exposed toward the intermembrane space. We find that cysteines in VDAC3 can stay in different oxidation states. This was preliminary observed when, in our experimental conditions, completely lacking any reducing agent, VDAC3 presented a pattern of slightly different electrophoretic mobilities. This observation holds true both for rat liver mitochondrial VDAC3 and for recombinant and refolded human VDAC3. Mass spectroscopy revealed that cysteines 2 and 8 can form a disulfide bridge in native VDAC3. Single or combined site-directed mutagenesis of cysteines 2, 8 and 122 showed that the protein mobility in SDS-PAGE is influenced by the presence of cysteine and by the redox status. In addition, cysteines 2, 8 and 122 are involved in the stability control of the pore as shown by electrophysiology, complementation assays and chemico-physical characterization. Furthermore, a positive correlation between the pore conductance of the mutants and their ability to complement the growth of porin-less yeast mutant cells was found. Our work provides evidence for a complex oxidation pattern of a mitochondrial protein not directly involved in electron transport. The most likely biological meaning of this behavior is to buffer the ROS load and keep track of the redox level in the intermembrane space, eventually signaling it through conformational change

Spontaneous polymerization of benzofulvene monomers bearing a 4-Pyri- dylacetylene substituent in different positions of the benzofulvene scaffold

Two benzofulvene derivatives bearing a 4-pyridylacetylene substituent in different positions (i. e. 2 and 6) of the benzofulvene scaffold are designed and synthesized to evaluate the effects on the spontaneous solid-state polymerization of the presence of the same substituent in two different key positions of the 3-phenylbenzoful-vene moiety. Both the benzofulvene derivatives showed the tendency to polymerize spontaneously in the consequence of solvent removal under reduced pressure without the addition of catalysts or initiators. The macromolecular structure of the stemming polymeric materials was investigated by NMR spectroscopy and MALDI-TOF mass spectrometry. Both NMR and MALDI-TOF studies confirmed the polymeric nature of the materials and suggested for the polybenzofulvene derivative bearing the 4-pyridylacetylene substituent in po-sitions 6 a higher structural homogeneity with respect to the one bearing the same substituent in position 2. The photophysical characterization of the most homogeneous polybenzofulvene derivative led to the discovery of its outstanding hole mobility value, which was found to be around one order of magnitude higher than that pre-viously measured for two oligothiophene-based polybenzofulvene derivatives and almost two orders of magni-tude higher than that of poly(vinylcarbazole), commonly used as hole-transporter matrix. This result places the new polybenzofulvene derivative in an outstanding position as a promising material for field-effect transistor (FET) device applications

Adding cetuximab to capecitabine plus oxaliplatin (XELOX) in first-line treatment of metastatic colorectal cancer: a randomized phase II trial of the Swiss Group for Clinical Cancer Research SAKK

Background: To determine the activity and tolerability of adding cetuximab to the oxaliplatin and capecitabine (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC). Patients and methods: In a multicenter two-arm phase II trial, patients were randomized to receive oxaliplatin 130 mg/m2 on day 1 and capecitabine 1000 mg/m2 twice daily on days 1-14 every 3 weeks alone or in combination with standard dose cetuximab. Treatment was limited to a maximum of six cycles. Results: Seventy-four patients with good performance status entered the trial. Objective partial response rates after external review and radiological confirmation were 14% and 41% in the XELOX and in the XELOX + Cetuximab arm, respectively. Stable disease has been observed in 62% and 35% of the patients, with 76% disease control in both arms. Cetuximab led to skin rash in 65% of the patients. The median overall survival was 16.5 months for arm A and 20.5 months for arm B. The median time to progression was 5.8 months for arm A and 7.2 months for arm B. Conclusion: Differences in response rates between the treatment arms indicate that cetuximab may improve outcome with XELOX. The correct place of the cetuximab, oxaliplatin and fluoropyrimidine combinations in first-line treatment of MCC has to be assessed in phase III trial

Generating long streams of 1/falpha1/f^alpha noise

We review existing methods for generating long streams of 1/f^alpha noise ($0<\alpha\le 2$) focusing on the digital filtering of white noise. We detail the formalism to conceive an efficient random number generator (white outside some bounds) in order to generate very long streams of noise without an exhaustive computer memory load. For $\alpha=2$ it is shown why the process is equivalent to a random-walk and can be obtained simply by a first order filtering of white noise. As soon as $\alpha<2$ the problem becomes non linear and we show why the exact digital filtering method becomes inefficient. Instead, we work out the formalism of using several 1/f^2 filters spaced logarithmically, to approximate the spectrum at the percent level. Finally, from work on logistic maps, we give hints on how to design generators with $\alpha>2$. The software is available from http://planck.lal.in2p3.fr/article.php3?id\_article=8Comment: Last version (corrected web site

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)

In this trial, stopping bevacizumab after completion of induction chemotherapy was associated with a shorter time to progression, but no statistically significant difference in overall survival compared with the bevacizumab continuation strategy. Non-inferiority could not be demonstrated. Treatment costs are substantially higher for continuous bevacizumab treatmen

Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes

It has been found that CDKL5 gene mutations are responsible for early-onset epilepsy and drug resistance. We screened a population of 92 patients with classic/atypical Rett syndrome, 17 Angelman/Angelman-like patients and six idiopathic autistic patients for CDKL5 mutations and exon deletions and identified seven novel mutations: six in the Rett subset and one in an Angelman patient. This last, an insertion in exon 11, c.903_904 dupGA, p.Leu302Aspfx49X, is associated with a relatively mild clinical presentation as the patient is the only one capable of sitting and walking alone. Of the six mutations, two are de novo missense changes affecting highly conserved aminoacid residues, c.215 T > C p.Ile72Thr and c.380A > G p.His127Arg (present in a mosaic condition) found in two girls with the most severe clinical presentation, while the remaining are the splicing c.145 + 2 T > C and c.2376 + 5G > A, the c.1648C > T p.Arg550X and the MPLA-identified c.162_99del261 mutation. RNA characterisation of four mutations revealed the aberrant transcript of the missense allele (case 2) and not the stop mutation (case 3), but also allowed the splicing mutation (case 1) and the c.-162_99del261 (case 4) to be ategorised as truncating. The obtained data reinforce the view that a more severe phenotype is due more to an altered protein than haploinsufficiency. Furthermore, the mutational repertoire of the CDKL5 gene is shown to be expanded by testing patients with phenotypical overlap to Rett syndrome and applying multiplex ligation-dependent probe amplification