Proline and glycine betaine accumulation in two succulent halophytes under natural and experimental conditions

[EN] Proline (Pro) and glycine betaine (GB) contents were determined in two Mediterranean halophytes, Plantago crassifolia and Inula crithmoides, to assess their possible role in salt tolerance of both taxa. Plant material was collected in a littoral salt marsh under different environmental conditions, and from plants subjected to salt treatments in a growth chamber. Relative growth inhibition by NaCl indicated that I. crithmoides is more salt-tolerant than P. crassifolia, in agreement with the distribution of the two species in nature. Field and laboratory data confirmed GB as the major osmolyte responsible for osmotic adjustment in I. crithmoides, but with only a minor role if any as osmoprotectant in the salt tolerance of P. crassifolia. Under natural conditions, Pro contents were very low in both taxa, but increased to levels high enough to contribute significantly to osmotic balance when plants were artificially treated with 450 600mM NaCl higher salt concentrations than those they would normally encounter in their natural habitats. These data suggest that halophytes possess built-in mechanisms, such as accumulation of additional osmolytes, to rapidly adapt to increasing salinity levels in their natural ecosystems; for example, those expected to be caused by climate change in salt marshes in the Mediterranean region.This work was funded by a grant to O.V. from the Spanish Ministry of Science and Innovation (Project CGL2008-00438/BOS), with contribution from the European Regional Development Fund. COST Action FA0901: "Putting Halophytes to work - From Genes to Ecosystems" supported M. N. Grigore for his stay in Valencia within the frame of a Short-Term Scientific Mission. A. Tifrea was funded by the Erasmus fellowship programme for her stay in Valencia to carry out her Master Thesis.Pardo-Domenech, L.; Tifrea, A.; Grigore, M.; Boscaiu, M.; Vicente, O. (2016). Proline and glycine betaine accumulation in two succulent halophytes under natural and experimental conditions. Plant Biosystems - An International Journal Dealing with all Aspects of Plant Biology. 150(5):904-915. https://doi.org/10.1080/11263504.2014.990943S904915150

BRAFV600E mutation in anaplastic thyroid carcinomas and their accompanying differentiated carcinomas

Frequency of a BRAFV600E mutation in anaplastic thyroid carcinoma, which is thought to be derived mainly from papillary carcinoma by multi-step carcinogenesis, is much lower than that in papillary carcinomas. To clarify this phenomenon, we analysed BRAFV600E mutation in 20 cases of anaplastic carcinoma and 13 accompanying differentiated carcinomas. Among twenty cases of anaplastic carcinomas, nine and four accompanied papillary and follicular carcinomas, respectively. BRAFV600E mutation was found in four (20%) cases. BRAFV600E mutation was found in three of nine (33.3%), none of four and one of seven (14.3%) anaplastic carcinomas with papillary carcinoma, follicular carcinoma and without differentiated components, respectively. All three papillary carcinomas accompanied by anaplastic carcinoma with a BRAFV600E mutation were also shown to have a BRAFV600E mutation. In summary, BRAFV600E mutation was occasionally observed in anaplastic carcinomas with papillary carcinoma, and the low frequency of BRAFV600E mutation in anaplastic carcinoma was thought to be due to the low frequency of anaplastic carcinomas with papillary carcinoma. These findings raise a question about the classical model of anaplastic transformation and suggest some roles of thyroid cancer stem cells in the generation of anaplastic carcinoma

SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1

BACKGROUND We have previously identified kinase suppressor of ras-1 (KSR1) as a potential regulatory gene in breast cancer. KSR1, originally described as a novel protein kinase, has a role in activation of mitogen-activated protein kinases. Emerging evidence has shown that KSR1 may have dual functions as an active kinase as well as a scaffold facilitating multiprotein complex assembly. Although efforts have been made to study the role of KSR1 in certain tumour types, its involvement in breast cancer remains unknown. METHODS A quantitative mass spectrometry analysis using stable isotope labelling of amino acids in cell culture (SILAC) was implemented to identify KSR1-regulated phosphoproteins in breast cancer. In vitro luciferase assays, co-immunoprecipitation as well as western blotting experiments were performed to further study the function of KSR1 in breast cancer. RESULTS Of significance, proteomic analysis reveals that KSR1 overexpression decreases deleted in breast cancer-1 (DBC1) phosphorylation. Furthermore, we show that KSR1 decreases the transcriptional activity of p53 by reducing the phosphorylation of DBC1, which leads to a reduced interaction of DBC1 with sirtuin-1 (SIRT1); this in turn enables SIRT1 to deacetylate p53. CONCLUSION Our findings integrate KSR1 into a network involving DBC1 and SIRT1, which results in the regulation of p53 acetylation and its transcriptional activity

Targeting BRAF in thyroid cancer

Activating mutations in the gene encoding BRAF are the most commonly identified oncogenic abnormalities in papillary thyroid cancer. In vitro and in vivo models have demonstrated that overexpression of activated BRAF induces malignant transformation and aggressive tumour behaviour. BRAF and other RAF kinases are frequently activated by other thyroid oncogenes and are important mediators of their biological effects including dedifferentiation and proliferation. Because current therapeutic options for patients with thyroid cancers that are aggressive and/or do not respond to standard therapies are limited, BRAF and its downstream effectors represent attractive therapeutic targets. In this review, data supporting a role for BRAF activation in thyroid cancer development and establishing the potential therapeutic efficacy of BRAF-targeted agents in patients with thyroid cancer will be reviewed

Size-Selected Ag Nanoparticles with Five-Fold Symmetry

Silver nanoparticles were synthesized using the inert gas aggregation technique. We found the optimal experimental conditions to synthesize nanoparticles at different sizes: 1.3 ± 0.2, 1.7 ± 0.3, 2.5 ± 0.4, 3.7 ± 0.4, 4.5 ± 0.9, and 5.5 ± 0.3 nm. We were able to investigate the dependence of the size of the nanoparticles on the synthesis parameters. Our data suggest that the aggregation of clusters (dimers, trimer, etc.) into the active zone of the nanocluster source is the predominant physical mechanism for the formation of the nanoparticles. Our experiments were carried out in conditions that kept the density of nanoparticles low, and the formation of larges nanoparticles by coalescence processes was avoided. In order to preserve the structural and morphological properties, the impact energy of the clusters landing into the substrate was controlled, such that the acceleration energy of the nanoparticles was around 0.1 eV/atom, assuring a soft landing deposition. High-resolution transmission electron microscopy images showed that the nanoparticles were icosahedral in shape, preferentially oriented with a five-fold axis perpendicular to the substrate surface. Our results show that the synthesis by inert gas aggregation technique is a very promising alternative to produce metal nanoparticles when the control of both size and shape are critical for the development of practical applications

A retrospective observational study of the relationship between single nucleotide polymorphisms associated with the risk of developing Colorectal cancer and survival

Background: There is variability in clinical outcome for patients with apparently the same stage colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) mapping to chromosomes 1q41, 3q26.2, 6p21, 8q23.3, 8q24.21, 10p14, 11q13, 11q23.1, 12q13.13, 14q22, 14q22.2, 15q13.3, 16q22.1, 18q21.1, 19q13.11, 20p12, 20p12.3, 20q13.33 and Xp22 have robustly been shown to be associated with the risk of developing CRC. Since germline variation can also influence patient outcome the relationship between these SNPs and patient survivorship from CRC was examined. Methods: All enrolled into the National Study of Colorectal Cancer Genetics (NSCCG) were genotyped for 1q41, 3q26.2, 6p21, 8q23.3, 8q24.21, 10p14, 11q13, 11q23.1, 12q13.13, 14q22, 14q22.2, 15q13.3, 16q22.1, 18q21.1, 19q13.11, 20p12, 20p12.3, 20q13.33 and xp22 SNPs. Linking this information to the National Cancer Data Repository allowed patient genotype to be related to survival. Results: The linked dataset consisted of 4,327 individuals. 14q22.22 genotype defined by the SNP rs4444235 showed a significant association with overall survival. Specifically, the C allele was associated with poorer observed survival (per allele hazard ratio 1.13, 95% confidence interval 1.05-1.22, P = 0.0015). Conclusion: The CRC susceptibility SNP rs4444235 also appears to exert an influence in modulating patient survival and warrants further evaluation as a potential prognostic marker

Identifying Highly Conserved and Highly Differentiated Gene Ontology Categories in Human Populations

Detecting and interpreting certain system-level characteristics associated with human population genetic differences is a challenge for human geneticists. In this study, we conducted a population genetic study using the HapMap genotype data to identify certain special Gene Ontology (GO) categories associated with high/low genetic difference among 11 Hapmap populations. Initially, the genetic differences in each gene region among these populations were measured using allele frequency, linkage disequilibrium (LD) pattern, and transferability of tagSNPs. The associations between each GO term and these genetic differences were then identified. The results showed that cellular process, catalytic activity, binding, and some of their sub-terms were associated with high levels of genetic difference, and genes involved in these functional categories displayed, on average, high genetic diversity among different populations. By contrast, multicellular organismal processes, molecular transducer activity, and some of their sub-terms were associated with low levels of genetic difference. In particular, the neurological system process under the multicellular organismal process category had low levels of genetic difference; the neurological function also showed high evolutionary conservation between species in some previous studies. These results may provide a new insight into the understanding of human evolutionary history at the system-level

Semi-supervised learning for the identification of syn-expressed genes from fused microarray and in situ image data

Background: Gene expression measurements during the development of the fly Drosophila melanogaster are routinely used to find functional modules of temporally co-expressed genes. Complimentary large data sets of in situ RNA hybridization images for different stages of the fly embryo elucidate the spatial expression patterns. Results: Using a semi-supervised approach, constrained clustering with mixture models, we can find clusters of genes exhibiting spatio-temporal similarities in expression, or syn-expression. The temporal gene expression measurements are taken as primary data for which pairwise constraints are computed in an automated fashion from raw in situ images without the need for manual annotation. We investigate the influence of these pairwise constraints in the clustering and discuss the biological relevance of our results. Conclusion: Spatial information contributes to a detailed, biological meaningful analysis of temporal gene expression data. Semi-supervised learning provides a flexible, robust and efficient framework for integrating data sources of differing quality and abundance

The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF (V600E) mutation

BRAF (V600E) mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF (V600E) on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF (V600E) mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF (V600E) mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.info:eu-repo/semantics/publishedVersio

A novel single nucleotide polymorphism within the NOD2 gene is associated with pulmonary tuberculosis in the Chinese Han, Uygur and Kazak populations

<p>Abstract</p> <p>Background</p> <p>The present study aimed to investigate the genetic polymorphisms in exon 4 of the <it>NOD2 </it>gene in tuberculosis patients and healthy controls, in order to clarify whether polymorphisms in the <it>NOD2 </it>gene is associated with tuberculosis.</p> <p>Methods</p> <p>A case-control study was performed on the Chinese Han, Uygur and Kazak populations. Exon 4 of the <it>NOD2 </it>gene was sequenced in 425 TB patients and 380 healthy controls to identify SNPs.</p> <p>Results</p> <p>The frequency of T/G genotypes for the Arg587Arg (CGT → CGG) single nucleotide polymorphism (SNP) in <it>NOD2 </it>was found to be significantly higher in the Uygur (34.9%) and Kazak (37.1%) populations than the Han population (18.6%). Also, the frequency of G/G genotypes for the Arg587Arg SNP was significantly higher in the Uyghur (8.3%) and Kazak (5.4%) populations than the Han population (0.9%). Meanwhile, no significant difference was found in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Uyghur and Kazak populations (<it>P </it>> 0.05) whereas, a significant difference was observed in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Han population (<it>P </it>< 0.01). The odd ratio of 2.16 (95% CI = 1.31-3.58; <it>P </it>< 0.01) indicated that the Arg587Arg SNP in <it>NOD2 </it>may be associated with susceptibility to tuberculosis in the Chinese Han population.</p> <p>Conclusions</p> <p>Our study is the first to demonstrate that the Arg587Arg SNP in <it>NOD2 </it>is a new possible risk factor for tuberculosis in the Chinese Han population, but not in the Uyghur and Kazak populations. Our results may reflect racial differences in genetic susceptibility to tuberculosis.</p