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排序方式: 共有596条查询结果,搜索用时 15 毫秒
541.
Daniel R Chevolot L Carrascal M Tissot B Mourão PA Abian J 《Carbohydrate research》2007,342(6):826-834
Algal fucoidan is a complex sulfated polysaccharide whose structural characterization requires powerful spectroscopic methodologies. While most of the structural investigations reported so far have been performed using NMR as the main spectroscopic method, we report herein data obtained by negative electrospray ionization mass spectrometry. MS analysis has been carried out on oligosaccharides obtained by partial hydrolysis of fucoidan from the brown algae Ascophyllum nodosum. Oligosaccharide mixtures were fractionated by size exclusion chromatography, which allowed the analysis of oligomers ranging from monosaccharide to pentasaccharide. Monosaccharides were detected as monosulfated as well as disulfated forms. Besides, part of the oligosaccharides exhibited a high content of sulfate, evidencing that fucoidan contains disulfated fucosyl units. Fragmentation experiments yielded characteristic fragment ions indicating that the fucose units are mainly 2-O-sulfated. This study demonstrates that highly sulfated oligosaccharides from fucoidan can be analyzed by ESIMS which gives additional information about the structure of this highly complex polysaccharide. 相似文献
542.
This perspective describes three new policies passed at the November 2020 Special Meeting of the American Medical Association House of Delegates. These policies (1) denounce racism as a public health threat; (2) call for the elimination of race as a proxy for ancestry, genetics, and biology in medical education, research, and clinical practice; and (3) decry racial essentialism in medicine. We also explore the social and institutional context leading to the passage of these policies, which speak directly to the harmful legacy of racism in America, and its insidious impact on the healthcare system. 相似文献
543.
Federico ávila-Moreno Leonel Armas-López Aldo M. álvarez-Moran Zoila López-Bujanda Blanca Ortiz-Quintero Alfredo Hidalgo-Miranda Francisco Urrea-Ramírez R. María Rivera-Rosales Eugenia Vázquez-Manríquez Erika Pe?a-Mirabal José Morales-Gómez Juan C. Vázquez-Minero José L. Téllez-Becerra Roberto Ramírez-Mendoza Alejandro ávalos-Bracho Enrique Guzmán de Alba Karla Vázquez-Santillán Vilma Maldonado-Lagunas Patricio Santillán-Doherty Patricia Pi?a-Sánchez Joaquin Zú?iga-Ramos 《PloS one》2014,9(12)
Lung cancer is the leading cause of death from malignant diseases worldwide, with the non-small cell (NSCLC) subtype accounting for the majority of cases. NSCLC is characterized by frequent genomic imbalances and copy number variations (CNVs), but the epigenetic aberrations that are associated with clinical prognosis and therapeutic failure remain not completely identify. In the present study, a total of 55 lung cancer patients were included and we conducted genomic and genetic expression analyses, immunohistochemical protein detection, DNA methylation and chromatin immunoprecipitation assays to obtain genetic and epigenetic profiles associated to prognosis and chemoresponse of NSCLC patients. Finally, siRNA transfection-mediated genetic silencing and cisplatinum cellular cytotoxicity assays in NSCLC cell lines A-427 and INER-37 were assessed to describe chemoresistance mechanisms involved. Our results identified high frequencies of CNVs (66–51% of cases) in the 7p22.3–p21.1 and 7p15.3–p15.2 cytogenetic regions. However, overexpression of genes, such as MEOX2, HDAC9, TWIST1 and AhR, at 7p21.2–p21.1 locus occurred despite the absence of CNVs and little changes in DNA methylation. In contrast, the promoter sequences of MEOX2 and TWIST1 displayed significantly lower/decrease in the repressive histone mark H3K27me3 and increased in the active histone mark H3K4me3 levels. Finally these results correlate with poor survival in NSCLC patients and cellular chemoresistance to oncologic drugs in NSCLC cell lines in a MEOX2 and TWIST1 overexpression dependent-manner. In conclusion, we report for the first time that MEOX2 participates in chemoresistance irrespective of high CNV, but it is significantly dependent upon H3K27me3 enrichment probably associated with aggressiveness and chemotherapy failure in NSCLC patients, however additional clinical studies must be performed to confirm our findings as new probable clinical markers in NSCLC patients. 相似文献
544.
Esperanza Gonzalez Marco Piva Eva Rodriguez-Suarez David Gil Felix Royo Felix Elortza Juan M. Falcon-Perez Maria dM. Vivanco 《PloS one》2014,9(1)
Breast cancer is a leading cause of cancer-associated death worldwide. One of the most important prognostic factors for survival is the early detection of the disease. Recent studies indicate that extracellular vesicles may provide diagnostic information for cancer management. We demonstrate the secretion of extracellular vesicles by primary breast epithelial cells enriched for stem/progenitor cells cultured as mammospheres, in non-adherent conditions. Using a proteomic approach we identified proteins contained in these vesicles whose expression is affected by hormonal changes in the cellular environment. In addition, we showed that these vesicles are capable of promoting changes in expression levels of genes involved in epithelial-mesenchymal transition and stem cell markers. Our findings suggest that secreted extracellular vesicles could represent potential diagnostic and/or prognostic markers for breast cancer and support a role for extracellular vesicles in cancer progression. 相似文献
545.
Integrating transcriptomic and metabolomic analysis to understand natural leaf senescence in sunflower
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Sebastián Moschen Sofía Bengoa Luoni Julio A. Di Rienzo María del Pilar Caro Takayuki Tohge Mutsumi Watanabe Julien Hollmann Sergio González Máximo Rivarola Francisco García‐García Joaquin Dopazo Horacio Esteban Hopp Rainer Hoefgen Alisdair R. Fernie Norma Paniego Ruth A. Heinz 《Plant biotechnology journal》2016,14(2):719-734
546.
Antonio Javier Moreno-Pérez Mónica Venegas-Calerón Fabián E. Vaistij Joaquin J. Salas Tony R. Larson Rafael Garcés Ian A. Graham Enrique Martínez-Force 《Planta》2014,239(3):667-677
The substrate specificity of the acyl–acyl carrier protein (ACP) thioesterases significantly determines the type of fatty acids that are exported from plastids. Thus, designing acyl-ACP thioesterases with different substrate specificities or kinetic properties would be of interest for plant lipid biotechnology to produce oils enriched in specialty fatty acids. In the present work, the FatA thioesterase from Helianthus annuus was used to test the impact of changes in the amino acids present in the binding pocket on substrate specificity and catalytic efficiency. Amongst all the mutated enzymes studied, Q215W was especially interesting as it had higher specificity towards saturated acyl-ACP substrates and higher catalytic efficiency compared to wild-type H. annuus FatA. Null, wild type and high-efficiency alleles were transiently expressed in tobacco leaves to check their effect on lipid biosynthesis. Expression of active FatA thioesterases altered the composition of leaf triacylglycerols but did not alter total lipid content. However, the expression of the wild type and the high-efficiency alleles in Arabidopsis thaliana transgenic seeds resulted in a strong reduction in oil content and an increase in total saturated fatty acid content. The role and influence of acyl-ACP thioesterases in plant metabolism and their possible applications in lipid biotechnology are discussed. 相似文献
547.
Isabel Molina-Ortiz Rub��n A. Bartolom�� Pablo Hern��ndez-Varas Georgina P. Colo Joaquin Teixid�� 《The Journal of biological chemistry》2009,284(22):15147-15157
Melanoma cells express the chemokine receptor CXCR4 that confers high
invasiveness upon binding to its ligand CXCL12. Melanoma cells at initial
stages of the disease show reduction or loss of E-cadherin expression, but
recovery of its expression is frequently found at advanced phases. We
overexpressed E-cadherin in the highly invasive BRO lung metastatic cell
melanoma cell line to investigate whether it could influence CXCL12-promoted
cell invasion. Overexpression of E-cadherin led to defective invasion of
melanoma cells across Matrigel and type I collagen in response to CXCL12. A
decrease in individual cell migration directionality toward the chemokine and
reduced adhesion accounted for the impaired invasion. A p190RhoGAP-dependent
inhibition of RhoA activation was responsible for the impairment in
chemokine-stimulated E-cadherin melanoma transfectant invasion. Furthermore,
we show that p190RhoGAP and p120ctn associated predominantly on the plasma
membrane of cells overexpressing E-cadherin, and that E-cadherin-bound p120ctn
contributed to RhoA inactivation by favoring p190RhoGAP-RhoA association.
These results suggest that melanoma cells at advanced stages of the disease
could have reduced metastatic potency in response to chemotactic stimuli
compared with cells lacking E-cadherin, and the results indicate that
p190RhoGAP is a central molecule controlling melanoma cell invasion.Cadherins are a family of Ca2+-dependent adhesion molecules that
mediate cell-cell contacts and are expressed in most solid tissues providing a
tight control of morphogenesis
(1,
2). Classical cadherins, such
as epithelial (E) cadherin, are found in adherens junctions, forming core
protein complexes with β-catenin, α-catenin, and p120 catenin
(p120ctn). Both β-catenin and p120ctn directly interact with E-cadherin,
whereas α-catenin associates with the complex through its binding to
β-catenin, providing a link with the actin cytoskeleton
(1,
2). E-cadherin is frequently
lost or down-regulated in many human tumors, coincident with morphological
epithelial to mesenchymal transition and acquisition of invasiveness
(3-6).Although melanoma only accounts for 5% of skin cancers, when metastasis
starts, it is responsible for 80% of deaths from skin cancers
(7). Melanocytes express
E-cadherin
(8-10),
but melanoma cells at early radial growth phase show a large reduction in the
expression of this cadherin, and surprisingly, expression has been reported to
be partially recovered by vertical growth phase and metastatic melanoma cells
(9,
11,
12).Trafficking of cancer cells from primary tumor sites to intravasation into
blood circulation and later to extravasation to colonize distant organs
requires tightly regulated directional cues and cell migration and invasion
that are mediated by chemokines, growth factors, and adhesion molecules
(13). Solid tumor cells
express chemokine receptors that provide guidance of these cells to organs
where their chemokine ligands are expressed, constituting a homing model
resembling the one used by immune cells to exert their immune surveillance
functions (14). Most solid
cancer cells express CXCR4, a receptor for the chemokine CXCL12 (also called
SDF-1), which is expressed in lungs, bone marrow, and liver
(15). Expression of CXCR4 in
human melanoma has been detected in the vertical growth phase and on regional
lymph nodes, which correlated with poor prognosis and increased mortality
(16,
17). Previous in vivo
experiments have provided evidence supporting a crucial role for CXCR4 in the
metastasis of melanoma cells
(18).Rho GTPases control the dynamics of the actin cytoskeleton during cell
migration (19,
20). The activity of Rho
GTPases is tightly regulated by guanine-nucleotide exchange factors
(GEFs),4 which
stimulate exchange of bound GDP by GTP, and inhibited by GTPase-activating
proteins (GAPs), which promote GTP hydrolysis
(21,
22), whereas guanine
nucleotide dissociation inhibitors (GDIs) appear to mediate blocking of
spontaneous activation (23).
Therefore, cell migration is finely regulated by the balance between GEF, GAP,
and GDI activities on Rho GTPases. Involvement of Rho GTPases in cancer is
well documented (reviewed in Ref.
24), providing control of both
cell migration and growth. RhoA and RhoC are highly expressed in colon,
breast, and lung carcinoma
(25,
26), whereas overexpression of
RhoC in melanoma leads to enhancement of cell metastasis
(27). CXCL12 activates both
RhoA and Rac1 in melanoma cells, and both GTPases play key roles during
invasion toward this chemokine
(28,
29).Given the importance of the CXCL12-CXCR4 axis in melanoma cell invasion and
metastasis, in this study we have addressed the question of whether changes in
E-cadherin expression on melanoma cells might affect cell invasiveness. We
show here that overexpression of E-cadherin leads to impaired melanoma cell
invasion to CXCL12, and we provide mechanistic characterization accounting for
the decrease in invasion. 相似文献
548.
Hassan Hosseini Monfared Joaquin Sanchiz Zahra Kalantari 《Inorganica chimica acta》2009,362(10):3791-3886
The in-situ formed hydrazone Schiff base ligand (E)-N′-(2-oxy-3-methoxybenzylidene)benzohydrazide (L2−) reacts with copper(II) acetate to a tetranuclear open cubane [Cu(L)]4 complex which crystallizes as two symmetry-independent (Z′ = 2) S4-symmetrical molecules in different twofold special positions with a homodromic water tetramer. The two independent (A and B) open- or pseudo-cubanes with Cu4O4 cores of 4 + 2 class (Ruiz classification) each have three different magnetic exchange pathways leading to an overall antiferromagnetic coupling with J1B = J2B = −17.2 cm−1, J1A = −36.7 cm−1, J2A = −159 cm−1, J3A = J3B = 33.5 cm−1, g = 2.40 and ρ = 0.0687. The magnetic properties have been analysed using the H = −Σi,jJij(SiSj) spin Hamiltonian. 相似文献
549.
The Escherichia coli HtrA protein is a periplasmic protease/chaperone that is upregulated under stress conditions. The protease and chaperone activities of HtrA eliminate or refold damaged and unfolded proteins in the bacterial periplasm that are generated upon stress conditions. In the absence of substrates, HtrA oligomerizes into a hexameric cage, but binding of misfolded proteins transforms the hexamers into bigger 12-mer and 24-mer cages that encapsulate the substrates for degradation or refolding. HtrA also undergoes partial degradation as a consequence of self-cleavage of the mature protein, producing short-HtrA protein (s-HtrA). The aim of this study was to examine the physiological role of this self-cleavage process. We found that the only requirement for self-cleavage of HtrA into s-HtrA in vitro was the hydrolysis of protein substrates. In fact, peptides resulting from the hydrolysis of the protein substrates were sufficient to induce autocleavage. However, the continuous presence of full-length substrate delayed the process. In addition, we observed that the hexameric cage structure is required for autocleavage and that s-HtrA accumulates only late in the degradation reaction. These results suggest that self-cleavage occurs when HtrA reassembles back into the resting hexameric structure and peptides resulting from substrate hydrolysis are allosterically stimulating the HtrA proteolytic activity. Our data support a model in which the physiological role of the self-cleavage process is to eliminate the excess of HtrA once the stress conditions cease.The cell envelope of gram-negative bacteria mediates the communication of the cell with the environment, and it is responsible for many vital functions, including nutrient uptake and interaction with other bacteria and host cells. These activities are performed by a large collection of proteins that make the periplasm a cellular compartment with an even higher protein concentration than the cytoplasm (2). Bacteria are frequently exposed to multiple stresses such as heat shock, osmotic stress, and pH changes and are regularly challenged by the host immune system. Thus, the maintenance of periplasmic proteins in a fully functional state is a challenging task undertaken by the protein quality control system (5). It is generally accepted that under stress conditions misfolded proteins, protein fragments, and mislocalized membrane proteins appear, activating a stress response through three different signal transduction pathways (σE, Cpx, and Bae) (21, 22). Activation of this stress response in the periplasm triggers the upregulation of molecular chaperones, peptidases, proteases, and other enzymes with a role in eliminating or refolding damaged periplasmic proteins.The Escherichia coli HtrA protein (also called DegP or protease Do) is a periplasmic protein (4) that is upregulated under stress conditions such as heat shock (14, 15). HtrA functions as a chaperone and a protease in a temperature-dependent fashion (24). Recent studies have also shown that HtrA substrates targeted for degradation or refolding are recognized differently, suggesting that the mechanisms through which HtrA recognizes the substrate may play a role in the protease-chaperone switch (8).HtrA contains an N-terminal protease domain, followed by the PDZ1 and PDZ2 domains. In the absence of substrates, HtrA oligomerizes into a hexameric cage (12) that represents the resting state of the protein (10, 13). Upon binding to protein substrates, HtrA transforms into bigger cages formed by 12 or 24 monomers that encapsulate substrates for degradation or refolding (9, 13).HtrA is a 474-residue protein whose first 26 amino acids are removed at the N terminus most likely by a signal peptidase rendering the mature 48-kDa protein (14, 15). This form of the protein will hereon be referred to as full-length HtrA. However, it has been described (11, 23) that mature HtrA undergoes partial degradation both in vivo and in vitro as a consequence of self-cleavage occurring after Cys69 and Gln82 of the mature protein. These forms of the protein have been named short-HtrA (s-HtrA) (23).A similar phenomenon of autocleavage has been observed in other members of the HtrA family such as the human homologs HtrA1 (7) and HtrA2 proteins (6). The autocleavage process is not specific for proteases of the HtrA family. Several prokaryotic proteins involved in regulation of gene expression, such as the SOS response proteins LexA (16-18) and UmuD (3), are inactivated through a self-cleaving mechanism. Conversely, many mammalian proteases are produced as longer inactive precursors and depend on an intramolecular cleavage event to become active. This is the case for some gastric proteases such as pepsin and chymosin or the lysosome cathepsins D and E (1).Although autocleavage as a mechanism of activation or inactivation of certain proteases is well documented, the physiological role and the events triggering the self-cleavage of HtrA are poorly understood. In this study, we observed that the hexameric cage structure is required to observe autocleavage of HtrA. In addition, we analyzed the conditions that led to self-cleavage of HtrA and we found that the only requirement to observe accumulation of the s-HtrA form in vitro was the hydrolysis of protein substrates. In fact, peptides resulting from the degradation of protein substrates were sufficient to induce autocleavage. Therefore, considering the current functional model for HtrA (9, 13), our data suggest that the physiological role of the HtrA autocleavage is to eliminate the excess of HtrA protein expressed under stress conditions when the enzymatic activities of the protein are no longer needed. 相似文献
550.