Extinction by Miscalculation:

Species at Risk Act, Sakinaw sockeye, Cultus sockeye, fisheries management, extinction.

Dangerous Liaisons: Circulating Tumor Cells (CTCs) and Cancer-Associated Fibroblasts (CAFs)

The crosstalk between cancer cells and the tumor microenvironment (TME) is a key determinant of cancer metastasis. Cancer-associated fibroblasts (CAFs), one of the main cellular components of TME, promote cancer cell invasion and dissemination through mechanisms including cell-cell interactions and the paracrine secretion of growth factors, cytokines and chemokines. During metastasis, circulating tumor cells (CTCs) are shed from the primary tumor to the bloodstream, where they can be detected as single cells or clusters. The current knowledge about the biology of CTC clusters positions them as key actors in metastasis formation. It also indicates that CTCs do not act alone and that they may be aided by stromal and immune cells, which seem to shape their metastatic potential. Among these cells, CAFs are found associated with CTCs in heterotypic CTC clusters, and their presence seems to increase their metastatic efficiency. In this review, we summarize the current knowledge on the role that CAFs play on metastasis and we discuss their implication on the biogenesis, metastasis-initiating capacity of CTC clusters, and clinical implications. Moreover, we speculate about possible therapeutic strategies aimed to limit the metastatic potential of CTC clusters involving the targeting of CAFs as well as their difficulties and limitations

Negociaci?n de bonos de reconocimiento en el mercado de valores peruano

Transcurridos 18 a?os de la creaci?n de los bonos de reconocimiento, que contienen un beneficio reconocido por el Estado a los trabajadores que optaron por trasladarse del Sistema Nacional de Pensiones (SNP) al Sistema Privado de Pensiones (SPP), nunca se dio la norma que autorizara su negociaci?n y hasta ahora no se ha transferido ninguno de estos t?tulos. El Estado ha venido pagando las obligaciones a trav?s de la Oficina de Normalizaci?n Previsional (ONP), pero los a?os de indecisi?n o burocracia han impedido que los tenedores de estos bonos puedan lograr beneficios mayores. Ante este panorama, es necesario revisar la normativa dada por las diferentes instituciones relacionadas con los bonos de reconocimiento y que ha generado algunas condiciones para la promulgaci?n en el futuro de una norma que sea la plataforma de lanzamiento de estos t?tulos en el mercado secundario de bonos. El principal objetivo de esta investigaci?n es analizar la factibilidad de negociar estos bonos como valores mobiliarios en el mercado secundario de valores de renta fija, tanto para generar mayor liquidez en el mercado de capitales peruano como para beneficiar a los afiliados de las AFP con mayores r?ditos, con lo que acumular?n mayores montos para su jubilaci?n. Se abordan aspectos conceptuales sobre los bonos de reconocimiento y se analiza y compara el mercado de deuda de valores mobiliarios a trav?s de las experiencias de Chile, El Salvador y Colombi

Evaluation of diversity among Argentine grapevine ( Vitis vinifera L.) varieties using morphological data and AFLP markers

Half of the Argentine grapevine growing area is cultivated with local varieties generically called "Criollas". These materials differ in morphology, physiology and enological aptitudes from traditional European varieties. To discriminate among them, we used morphological markers to evaluate the genetic diversity and phenetic relatedness of 9 Criollas, 6 European and 1 American varieties and compared with AFLP markers. Three AFLP primer combinations generated a total of 111 scorable fragments. Dendrograms obtained with morphologic and AFLP markers agreed in clustering the "Criollas" separately from the European and American varieties assayed, except for Muscat d' Alexandrie and Tempranillo which clustered with Criollas in the case of AFLP. Comparison of UPGMA dendrograms of morphological and AFLP markers using the Mantel test indicated a not significant correlation of r = 0.33. Nevertheless, AFLP and selected morphological characters appear as useful and complementary techniques for grapevine identification and for evaluation of genetic diversity. Among the "Criollas", AFLP similarities ranged from 76 to 98% (Dice coefficient), indicating an important source of genetic diversity that can be exploited in future breeding programs. To our knowledge, this is the first report using AFLP markers to assess genetic variability on these materials

Small-Molecule Ligands that Bind the RET Receptor Activate Neuroprotective Signals Independent of but Modulated by Coreceptor GFR alpha 1

Glial cell line-derived neurotrophic factor (GDNF) binds the GFR alpha 1 receptor, and the GDNF-GFR alpha 1 complex binds to and activates the transmembrane RET tyrosine kinase to signal through intracellular Akt/Erk pathways. To dissect the GDNF-GFR alpha 1-RET signaling complex, agents that bind and activate RET directly and independently of GFR alpha 1 expression are valuable tools. In a focused naphthalenesulfonic acid library from the National Cancer Institute database, we identified small molecules that are genuine ligands binding to the RET extracellular domain. These ligands activate RET tyrosine kinase and afford trophic signals irrespective of GFR alpha 1 coexpression. However, RET activation by these ligands is constrained by GFR alpha 1, likely via an allosteric mechanism that can be overcome by increasing RET ligand concentration. In a mouse model of retinitis pigmentosa, monotherapy with a small-molecule RET agonist activates survival signals and reduces neuronal death significantly better than GDNF, suggesting therapeutic potential. SIGNIFICANCE STATEMENT A genuine ligand of RET receptor ectodomain was identified, which acts as an agonist. Binding and agonism are independent of a coreceptor glial cell line-derived neurotrophic factor family receptor a, which is required by the natural growth factor glial cell line-derived neurotrophic factor, and are selective for cells expressing RET. The lead agent protects neurons from death in vivo. This work validates RET receptor as a druggable therapeutic target and provides for potential leads to evaluate in neurodegenerative states. We also report problems that arise when screening chemical libraries.Peer reviewe

Cytotoxic Acetogenins from the Roots of Annona purpurea

Annona purpurea, known in Mexico as "cabeza de negro" or "ilama", belongs to the Annonaceae family. Its roots are employed in folk medicine in several regions of Mexico. Taking that information into account, a chemical and biological analysis of the components present in the roots of this species was proposed. Our results demonstrated that the dichloromethane (DCM) extract was exclusively constituted by a mixture of five new acetogenins named annopurpuricins A-E (1-5). These compounds have an aliphatic chain of 37 carbons with a terminal \u3b1,\u3b2 unsaturated \u3b3-lactone. Compounds 1 and 2 belong to the adjacent bis-THF (tetrahydrofuran) \u3b1-monohydroxylated type, while compounds 3 and 4 belong to the adjacent bis-THF \u3b1,\u3b1'-dihydroxylated type; only compound 5 possesses a bis-epoxide system. Complete structure analysis was carried out by spectroscopy and chemical methods. All compounds were evaluated for their antiproliferative activity on three human tumor cell lines (MSTO-211H, HeLa and HepG2). Compounds 1-4 inhibited significantly the growth of HeLa and HepG2 cells, showing GI50 values in the low/subnanomolar range, while 5 was completely ineffective under the tested conditions. The investigation of the mechanism of action responsible for cytotoxicity revealed for the most interesting compound 1 the ability to block the complex I activity on isolated rat liver mitochondria (RLM)

Callus culture development of two varieties of Tagetes erecta and carotenoid production

Background: The properties of natural pigments, such as antioxidants, functional,medical, and nutraceutical, have demonstrated the advantages of these natural compounds over synthetic ones. Some products are accepted only when they are pigmented with natural, food-quality colorants: for example poultry products (manly marigold flower extracts). Carotenoids such as \u3b2-carotene, \u3b2-criptoxanthin and lutein are very attractive as natural food colorants due to their antioxidant and pro-vitamin activities which provide additional value to the target products. Marigold ( Tagetes erecta ) is an Asteraceous ornamental plant native to Mexico, and it is also important as a carotenoid source for industrial and medicinal purposes but nowadays its production is destined mainly for ornamental purposes. Results: Friable callus of T. erecta yellow flower (YF) and white flower (WF) varieties was induced from leaf explants on Murashige and Skoog (MS) medium supplemented with 9.0 \u3bcM 4-dichlorophenoxyacetic acid (2,4-D) and 8.8 \u3bcM benzyladenine (BA). Calluses developed from both varieties were different in pigmentation. Extract characterization from callus cultures was carried out by high-performance liquid chromatography (HPLC). This analytical process detected several carotenoids; the main pigments in extracts from YF callus were lutein and zeaxanthin, whereas in the extracts of the WF callus the main pigmentswere lutein, zeaxanthin, \u3b2-cryptoxanthin and \u3b2-carotene. Callus cultures of T. erecta accumulated pigments even after several rounds of subculture. Conclusions: WF callus appeared to be a suitable candidate as a source of different carotenoids, and tested varieties could represent an alternative for further studies about in vitro pigment production

Microsatellite markers in candidate genes for wood properties and its application in functional diversity assessment in Eucalyptus globulus

Background: Functional genetic markers have important implications for genetic analysis by providing direct estimation of functional diversity. Although high throughput sequencing techniques for functional diversity analysis are being developed nowadays, the use of already well established variable markers present in candidate genes is still an interesting alternative for mapping purposes and functional diversity studies. SSR markers are routinely used in most plant and animal breeding programs for many species including Eucalyptus . SSR markers derived from candidate genes (SSR-CG) can be used effectively in co-segregation studies and marker-assisted diversity management. Results: In the present study, eight new non reported SSRs were identified in seven candidate genes for wood properties in Eucalyptus globulus : cinnamoyl CoA reductase (CCR), homocysteine S-methyltransferase (HMT), shikimate kinase (SK), xyloglucan endotransglycosylase 2 (XTH2), cellulose synthase 3 (CesA3), glutathione S-transferase (GST) and the transcription factor LIM1. Microsatellites were located in promoters, introns and exons, being most of them CT dinucleotide repeats. Genetic diversity of these eight CG-derived SSR-markers was explored in 54 unrelated genotypes. Except for XTH2, high levels of polymorphism were detected: 93 alleles (mean of 13.1 sd 1.6 alleles per locus), a mean effective number of alleles (Ne) of 5.4 (sd 1.6), polymorphic information content values (PIC) from 0.617 to 0.855 and probability of Identity (PI) ranging from 0.030 to 0.151. Conclusions: This is the first report on the identification, characterization and diversity analysis of microsatellite markers located inside wood quality candidate genes (CG) from Eucalyptus globulus. This set of markers is then appropriate for characterizing genetic variation, with potential usefulness for quantitative trait loci (QTL) mapping in different eucalypts genetic pedigrees and other applications such as fingerprinting and marker assisted diversity management

Plasma lipidome and risk of atrial fibrillation: results from the PREDIMED trial

The potential role of the lipidome in atrial fibrillation (AF) development is still widely unknown. We aimed to assess the association between lipidome profiles of the Prevenci\uf3n con Dieta Mediterr\ue1nea (PREDIMED) trial participants and incidence of AF. We conducted a nested case–control study (512 incident centrally adjudicated AF cases and 735 controls matched by age, sex, and center). Baseline plasma lipids were profiled using a Nexera X2 U-HPLC system coupled to an Exactive Plus orbitrap mass spectrometer. We estimated the association between 216 individual lipids and AF using multivariable conditional logistic regression and adjusted the p values for multiple testing. We also examined the joint association of lipid clusters with AF incidence. Hitherto, we estimated the lipidomics network, used machine learning to select important network-clusters and AF-predictive lipid patterns, and summarized the joint association of these lipid patterns weighted scores. Finally, we addressed the possible interaction by the randomized dietary intervention. Forty-one individual lipids were associated with AF at the nominal level (p < 0.05), but no longer after adjustment for multiple-testing. However, the network-based score identified with a robust data-driven lipid network showed a multivariable-adjusted ORper+1SD of 1.32 (95% confidence interval: 1.16–1.51; p < 0.001). The score included PC plasmalogens and PE plasmalogens, palmitoyl-EA, cholesterol, CE 16:0, PC 36:4;O, and TG 53:3. No interaction with the dietary intervention was found. A multilipid score, primarily made up of plasmalogens, was associated with an increased risk of AF. Future studies are needed to get further insights into the lipidome role on AF. Current Controlled Trials number, ISRCTN35739639