Effect of Exogenously Applied 24-Epibrassinolide and Brassinazole on Xylogenesis and Microdistribution of Cell Wall Polymers in Leucaena leucocephala (Lam) De Wit

Plant growth regulators play a key role in cell wall structure and chemistry of woody plants. Understanding of these regulatory signals is important in advanced research on wood quality improvement in trees. The present study is aimed to investigate the influence of exogenous application of 24-epibrassinolide (EBR) and brassinosteroid inhibitor, brassinazole (BRZ) on wood formation and spatial distribution of cell wall polymers in the xylem tissue of Leucaena leucocephala using light and immuno electron microscopy methods. Brassinazole caused a decrease in cambial activity, xylem differentiation, length and width of fibres, vessel element width and radial extent of xylem suggesting brassinosteroid inhibition has a concomitant impact on cell elongation, expansion and secondary wall deposition. Histochemical studies of 24-epibrassinolide treated plants showed an increase in syringyl lignin content in the xylem cell walls. Fluorescence microscopy and transmission electron microscopy studies revealed the inhomogenous pattern of lignin distribution in the cell corners and middle lamellae region of BRZ treated plants. Immunolocalization studies using LM10 and LM 11 antibodies have shown a drastic change in the micro-distribution pattern of less substituted and highly substituted xylans in the xylem fibres of plants treated with EBR and BRZ. In conclusion, present study demonstrates an important role of brassinosteroid in plant development through regulating xylogenesis and cell wall chemistry in higher plants

VEGF and TGF-β are required for the maintenance of the choroid plexus and ependyma

Although the role of vascular endothelial growth factor (VEGF) in developmental and pathological angiogenesis is well established, its function in the adult is less clear. Similarly, although transforming growth factor (TGF) β is involved in angiogenesis, presumably by mediating capillary (endothelial cell [EC]) stability, its involvement in quiescent vasculature is virtually uninvestigated. Given the neurological findings in patients treated with VEGF-neutralizing therapy (bevacizumab) and in patients with severe preeclampsia, which is mediated by soluble VEGF receptor 1/soluble Fms-like tyrosine kinase receptor 1 and soluble endoglin, a TGF-β signaling inhibitor, we investigated the roles of VEGF and TGF-β in choroid plexus (CP) integrity and function in adult mice. Receptors for VEGF and TGF-β were detected in adult CP, as well as on ependymal cells. Inhibition of VEGF led to decreased CP vascular perfusion, which was associated with fibrin deposition. Simultaneous blockade of VEGF and TGF-β resulted in the loss of fenestrae on CP vasculature and thickening of the otherwise attenuated capillary endothelium, as well as the disappearance of ependymal cell microvilli and the development of periventricular edema. These results provide compelling evidence that both VEGF and TGF-β are involved in the regulation of EC stability, ependymal cell function, and periventricular permeability

Root and Leaf Anatomy, Ion Accumulation, and Transcriptome Pattern under Salt Stress Conditions in Contrasting Genotypes of Sorghum bicolor

Roots from salt-susceptible ICSR-56 (SS) sorghum plants display metaxylem elements with thin cell walls and large diameter. On the other hand, roots with thick, lignified cell walls in the hypodermis and endodermis were noticed in salt-tolerant CSV-15 (ST) sorghum plants. The secondary wall thickness and number of lignified cells in the hypodermis have increased with the treatment of sodium chloride stress to the plants (STN). Lignin distribution in the secondary cell wall of sclerenchymatous cells beneath the lower epidermis was higher in ST leaves compared to the SS genotype. Casparian thickenings with homogenous lignin distribution were observed in STN roots, but inhomogeneous distribution was evident in SS seedlings treated with sodium chloride (SSN). Higher accumulation of K+ and lower Na+ levels were noticed in ST compared to the SS genotype. To identify the differentially expressed genes among SS and ST genotypes, transcriptomic analysis was carried out. Both the genotypes were exposed to 200 mM sodium chloride stress for 24 h and used for analysis. We obtained 70 and 162 differentially expressed genes (DEGs) exclusive to SS and SSN and 112 and 26 DEGs exclusive to ST and STN, respectively. Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis unlocked the changes in metabolic pathways in response to salt stress. qRT-PCR was performed to validate 20 DEGs in each SSN and STN sample, which confirms the transcriptomic results. These results surmise that anatomical changes and higher K+/Na+ ratios are essential for mitigating salt stress in sorghum apart from the genes that are differentially up- and downregulated in contrasting genotypes

Quantum teleportation and state sharing using a genuinely entangled six qubit state

The usefulness of the genuinely entangled six qubit state that was recently introduced by Borras et al. is investigated for the quantum teleportation of an arbitrary three qubit state and for quantum state sharing (QSTS) of an arbitrary two qubit state. For QSTS, we explicitly devise two protocols and construct sixteen orthogonal measurement basis which can lock an arbitrary two qubit information between two parties.Comment: 6 pages, 7 table

FLT1 and transcriptome-wide polyadenylation site (PAS) analysis in preeclampsia

Maternal symptoms of preeclampsia (PE) are primarily driven by excess anti-angiogenic factors originating from the placenta. Chief among these are soluble Flt1 proteins (sFlt1s) produced from alternatively polyadenylated mRNA isoforms. Here we used polyadenylation site sequencing (PAS-Seq) of RNA from normal and PE human placentae to interrogate transcriptome-wide gene expression and alternative polyadenylation signatures associated with early-onset PE (EO-PE; symptom onset 34 weeks) cohorts. While we observed no general shift in alternative polyadenylation associated with PE, the EO-PE and LO-PE cohorts do exhibit gene expression profiles distinct from both each other and from normal placentae. The only two genes upregulated across all transcriptome-wide PE analyses to date (microarray, RNA-Seq and PAS-Seq) are NRIP1 (RIP140), a transcriptional co-regulator linked to metabolic syndromes associated with obesity, and Flt1. Consistent with sFlt1 overproduction being a significant driver of clinical symptoms, placental Flt1 mRNA levels strongly correlate with maternal blood pressure. For Flt1, just three mRNA isoforms account for > 94% of all transcripts, with increased transcription of the entire locus driving Flt1 upregulation in both EO-PE and LO-PE. These three isoforms thus represent potential targets for therapeutic RNA interference (RNAi) in both early and late presentations

First-Trimester Follistatin-Like-3 Levels in Pregnancies Complicated by Subsequent Gestational Diabetes Mellitus

Objective: To determine whether maternal levels of follistatin-like-3 (FSTL3), an inhibitor of activin and myostatin involved in glucose homeostasis, are altered in the first trimester of pregnancies complicated by subsequent gestational diabetes mellitus (GDM). Research Design and Methods: This was a nested case-control study of subjects enrolled in a prospective cohort of pregnant women with and without GDM ($\geq$2 abnormal values on a 100-g glucose tolerance test at ~28 weeks of gestation). We measured FSTL3 levels in serum collected during the first trimester of pregnancy. Logistic regression analyses were used to determine the risk of GDM. Results: Women who developed GDM (n = 37) had lower first-trimester serum levels of FSTL3 compared with women who did not (n = 127) (median 10,789 [interquartile range 7,013-18,939] vs. 30,670 [18,370-55,484] pg/ml, P < 0.001). When subjects were divided into tertiles based on FSTL3 levels, women with the lowest levels demonstrated a marked increase in risk for developing GDM in univariate (odds ratio 11.2 [95% CI 3.6-35.3]) and multivariate (14.0 [4.1-47.9]) analyses. There was a significant negative correlation between first-trimester FSTL3 levels and ~28-week nonfasting glucose levels (r = -0.30, P < 0.001). Conclusions: First-trimester FSTL3 levels are associated with glucose intolerance and GDM later in pregnancy

RETRATO SIN IDENTIFICAR [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte, 201

Vemurafenib-resistance via de novo RBM genes mutations and chromosome 5 aberrations is overcome by combined therapy with palbociclib in thyroid carcinoma with BRAFV600E

Purpose Papillary thyroid carcinoma (PTC) is the most frequent endocrine tumor. BRAFV600E represents the PTC hallmark and is targeted with selective inhibitors (e.g. vemurafenib). Although there have been promising results in clinical trials using these inhibitors, most patients develop resistance and progress. Tumor clonal diversity is proposed as one mechanism underlying drug resistance. Here we have investigated mechanisms of primary and secondary resistance to vemurafenib in BRAFWT/V600E–positive PTC patient-derived cells with P16-/- (CDKN2A-/-). Experimental Design Following treatment with vemurafenib, we expanded a sub-population of cells with primary resistance and characterized them genetically and cytogenetically. We have used exome sequencing, metaphase chromosome analysis, FISH and oligonucleotide SNP-microarray assays to assess clonal evolution of vemurafenib-resistant cells. Furthermore, we have validated our findings by networks and pathways analyses using PTC clinical samples. Results: Vemurafenib-resistant cells grow similarly to naïve cells but are refractory to apoptosis upon treatment with vemurafenib, and accumulate in G2-M phase. We find that vemurafenib-resistant cells show amplification of chromosome 5 and de novo mutations in the RBM (RNA-binding motifs) genes family (i.e. RBMX, RBM10). RBMX knockdown in naïve-cells contributes to tetraploidization, including expansion of clones with chromosome 5 aberrations (e.g. isochromosome 5p). RBMX elicits gene regulatory networks with chromosome 5q cancer-associated genes and pathways for G2-M and DNA damage-response checkpoint regulation in BRAFWT/V600E-PTC. Importantly, combined therapy with vemurafenib plus palbociclib (inhibitor of CDK4/6, mimicking P16 functions) synergistically induces stronger apoptosis than single agents in resistant-cells and in anaplastic thyroid tumor cells harboring the heterozygous BRAFWT/V600E mutation. Conclusions: Critically, our findings suggest for the first time that targeting BRAFWT/V600E and CDK4/6 represents a novel therapeutic strategy to treat vemurafenib-resistant or vemurafenib-naïve radioiodine-refractory BRAFWT/V600E-PTC. This combined therapy could prevent selection and expansion of aggressive PTC cell sub-clones with intrinsic resistance, targeting tumor cells either with primary or secondary resistance to BRAFV600E inhibitor