Observation of a Charge Density Wave Incommensuration Near the Superconducting Dome in Cu_{x}TiSe_{2}.

X-ray diffraction was employed to study the evolution of the charge density wave (CDW) in Cu_{x}TiSe_{2} as a function of copper intercalation in order to clarify the relationship between the CDW and superconductivity. The results show a CDW incommensuration arising at an intercalation value coincident with the onset of superconductivity at around x=0.055(5). Additionally, it was found that the charge density wave persists to higher intercalant concentrations than previously assumed, demonstrating that the CDW does not terminate inside the superconducting dome. A charge density wave peak was observed in samples up to x=0.091(6), the highest copper concentration examined in this study. The phase diagram established in this work suggests that charge density wave incommensuration may play a role in the formation of the superconducting state

Further Delineation of Duplications of ARX Locus Detected in Male Patients with Varying Degrees of Intellectual Disability

The X-linked gene encoding aristaless-related homeobox (ARX) is a bi-functional transcription factor capable of activating or repressing gene transcription, whose mutations have been found in a wide spectrum of neurodevelopmental disorders (NDDs); these include cortical malformations, pae-diatric epilepsy, intellectual disability (ID) and autism. In addition to point mutations, duplications of the ARX locus have been detected in male patients with ID. These rearrangements include telen-cephalon ultraconserved enhancers, whose structural alterations can interfere with the control of ARX expression in the developing brain. Here, we review the structural features of 15 gain copy-number variants (CNVs) of the ARX locus found in patients presenting wide-ranging phenotypic variations including ID, speech delay, hypotonia and psychiatric abnormalities. We also report on a further novel Xp21.3 duplication detected in a male patient with moderate ID and carrying a fully duplicated copy of the ARX locus and the ultraconserved enhancers. As consequences of this rearrangement, the patient-derived lymphoblastoid cell line shows abnormal activity of the ARX-KDM5C-SYN1 regulatory axis. Moreover, the three-dimensional (3D) structure of the Arx locus, both in mouse embryonic stem cells and cortical neurons, provides new insight for the functional consequences of ARX duplications. Finally, by comparing the clinical features of the 16 CNVs affecting the ARX locus, we conclude that—depending on the involvement of tissue-specific enhancers—the ARX duplications are ID-associated risk CNVs with variable expressivity and penetrance

Mitochondrial and endoplasmic reticulum stress pathways cooperate in zearalenone-induced apoptosis of human leukemic cells

<p>Abstract</p> <p>Background</p> <p>Zearalenone (ZEA) is a phytoestrogen from <it>Fusarium </it>species. The aims of the study was to identify mode of human leukemic cell death induced by ZEA and the mechanisms involved.</p> <p>Methods</p> <p>Cell cytotoxicity of ZEA on human leukemic HL-60, U937 and peripheral blood mononuclear cells (PBMCs) was performed by using 3-(4,5-dimethyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Reactive oxygen species production, cell cycle analysis and mitochondrial transmembrane potential reduction was determined by employing 2',7'-dichlorofluorescein diacetate, propidium iodide and 3,3'-dihexyloxacarbocyanine iodide and flow cytometry, respectively. Caspase-3 and -8 activities were detected by using fluorogenic Asp-Glu-Val-Asp-7-amino-4-methylcoumarin (DEVD-AMC) and Ile-Glu-Thr-Asp-7-amino-4-methylcoumarin (IETD-AMC) substrates, respectively. Protein expression of cytochrome c, Bax, Bcl-2 and Bcl-xL was performed by Western blot. The expression of proteins was assessed by two-dimensional polyacrylamide gel-electrophoresis (PAGE) coupled with LC-MS2 analysis and real-time reverse transcription polymerase chain reaction (RT-PCR) approach.</p> <p>Results</p> <p>ZEA was cytotoxic to U937 > HL-60 > PBMCs and caused subdiploid peaks and G1 arrest in both cell lines. Apoptosis of human leukemic HL-60 and U937 cell apoptosis induced by ZEA was via an activation of mitochondrial release of cytochrome c through mitochondrial transmembrane potential reduction, activation of caspase-3 and -8, production of reactive oxygen species and induction of endoplasmic reticulum stress. Bax was up regulated in a time-dependent manner and there was down regulation of Bcl-xL expression. Two-dimensional PAGE coupled with LC-MS2 analysis showed that ZEA treatment of HL-60 cells produced differences in the levels of 22 membrane proteins such as apoptosis inducing factor and the ER stress proteins including endoplasmic reticulum protein 29 (ERp29), 78 kDa glucose-regulated protein, heat shock protein 90 and calreticulin, whereas only <it>ERp29 </it>mRNA transcript increased.</p> <p>Conclusion</p> <p>ZEA induced human leukemic cell apoptosis via endoplasmic stress and mitochondrial pathway.</p

Plant lectins: the ties that bind in root symbiosis and plant defense

Lectins are a diverse group of carbohydrate-binding proteins that are found within and associated with organisms from all kingdoms of life. Several different classes of plant lectins serve a diverse array of functions. The most prominent of these include participation in plant defense against predators and pathogens and involvement in symbiotic interactions between host plants and symbiotic microbes, including mycorrhizal fungi and nitrogen-fixing rhizobia. Extensive biological, biochemical, and molecular studies have shed light on the functions of plant lectins, and a plethora of uncharacterized lectin genes are being revealed at the genomic scale, suggesting unexplored and novel diversity in plant lectin structure and function. Integration of the results from these different types of research is beginning to yield a more detailed understanding of the function of lectins in symbiosis, defense, and plant biology in general

Genotyping-by-sequencing reveals molecular genetic diversity in Italian common bean landraces

The common bean (Phaseolus vulgaris L.) is one of the main legumes worldwide and represents a valuable source of nutrients. Independent domestication events in the Americas led to the formation of two cultivated genepools, namely Mesoamerican and Andean, to which European material has been brought back. In this study, Italian common bean landraces were analyzed for their genetic diversity and structure, using single nucleotide polymorphism (SNP) markers derived from genotyping-by-sequencing (GBS) technology. After filtering, 11,866 SNPs were obtained and 798 markers, pruned for linkage disequilibrium, were used for structure analysis. The most probable number of subpopulations (K) was two, consistent with the presence of the two genepools, identified through the phaseolin diagnostic marker. Some landraces were admixed, suggesting probable hybridization events between Mesoamerican and Andean material. When increasing the number of possible Ks, the Andean germplasm appeared to be structured in two or three subgroups. The subdivision within the Andean material was also observed in a principal coordinate analysis (PCoA) plot and a dendrogram based on genetic distances. The Mesoamerican landraces showed a higher level of genetic diversity compared to the Andean landraces. Calculation of the fixation index (FST) at individual SNPs between the Mesoamerican and Andean genepools and within the Andean genepool evidenced clusters of highly divergent loci in specific chromosomal regions. This work may help to preserve landraces of the common bean from genetic erosion, and could represent a starting point for the identification of interesting traits that determine plant adaptation