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  • Reduced intestinal tumorigenesis in APCmin mice lacking melanin-concentrating hormone. 22848656

    Melanin-concentrating hormone (MCH) is an evolutionary conserved hypothalamic neuropeptide that in mammals primarily regulates appetite and energy balance. We have recently identified a novel role for MCH in intestinal inflammation by demonstrating attenuated experimental colitis in MCH deficient mice or wild type mice treated with an anti-MCH antibody. Therefore, targeting MCH has been proposed for the treatment of inflammatory bowel disease. Given the link between chronic intestinal inflammation and colorectal cancer, in the present study we sought to investigate whether blocking MCH might have effects on intestinal tumorigenesis that are independent of inflammation.
    Tipo de documento:
    Referencia
    Referencia del producto:
    S7100
    Nombre del producto:
    ApopTag® Peroxidase In Situ Apoptosis Detection Kit

  • Periostin is Down-regulated during Periodontal Inflammation. 22933606

    Periostin, a matricellular adapter protein highly expressed by periodontal ligament fibroblasts, is implicated in the maintenance of periodontal integrity, which is compromised during periodontal diseases. The aim of this study was to explore the influence of chronic periodontal inflammation on tissue periostin levels. Periodontal breakdown was induced in a pre-clinical ligature periodontal inflammatory disease model. Periodontal tissue specimens were harvested at baseline, 2 weeks, and 4 weeks and prepared for histologic, immunofluorescence, and micro-CT examination. Statistical analyses were conducted by Kruskal-Wallis, Mann-Whitney, and Spearman's tests. Periostin detection levels were reduced over time in response to the inflammatory process (1 ± 0.05; 0.67 ± 0.03; 0.31 ± 0.02; p < 0.001; baseline, 2, and 4 weeks, respectively). Simultaneously, alveolar bone loss increased from baseline to the 2- and 4-week time-points (0.40 ± 0.02 mm; 1.39 ± 0.08 mm; 1.33 ± 0.15 mm; p < 0.001), which was inversely correlated with the levels of periostin (ρ = -0.545; p < 0.001). In conclusion, periostin PDL tissue levels significantly decrease under chronic inflammatory response and correlate with the detrimental changes to the periodontium over time.
    Tipo de documento:
    Referencia
    Referencia del producto:
    S7100
    Nombre del producto:
    ApopTag® Peroxidase In Situ Apoptosis Detection Kit

  • Biologic significance of fascin expression in clear cell renal cell carcinoma: systematic analysis of primary and metastatic tumor tissues using a tissue microarray techn ... 16979727

    OBJECTIVES: To investigate the biologic significance of fascin, a globular actin cross-linking protein, involved in cell adhesion and motility, in primary and metastatic renal cell carcinoma (RCC). METHODS: A total of 136 primary clear cell RCCs and 54 clear cell RCC metastases were stained immunohistochemically using a tissue microarray technique. Distinct cytoplasmic staining was considered positive, and the staining results were associated with the pT stage, Fuhrman grade, tumor size, sarcomatoid morphology, and metastasis-free survival. For multivariate testing, Cox's proportional hazards regression model was used. RESULTS: Fascin expression was noted in 13 (10%) of 136 primary and 25 (46%) of 54 metastatic RCC specimens (P 0.001). Fascin expression was associated with high tumor stage (2 [3%] of 70 pT1 versus 11 [17%] of pT2/pT3; P = 0.008), high tumor grade (3 [3%] of 88 grade 1-2 versus 10 [21%] of 48 grade 3-4; P = 0.002), and large tumor size (P 0.001). In addition, 8 (62%) of 13 RCCs with sarcomatoid morphology expressed fascin compared with 5 (4%) of 123 RCCs without sarcomatoid transformation (P 0.001). Metastatic disease was noted in 10 (77%) of 13 patients with fascin-positive RCC compared with 26 (21%) of 121 patients with fascin-negative RCC (P 0.001). Multivariate analysis revealed pT Stage 1 or greater (P 0.001, risk ratio [RR] 8.6, 95% confidence interval [CI] 2.8 to 26.5), Fuhrman grade greater than 2 (P 0.001, RR 12.7, 95% CI 4.6 to 35.4), fascin expression (P 0.001, RR 7.2, 95% CI 3.0 to 17.4), and female gender (P = 0.02, RR 2.5, 95% CI 1.1 to 5.5) as independent predictors of metastatic disease. CONCLUSIONS: Fascin immunoreactivity in RCC proved to be an independent predictor of metastatic disease and was demonstrated in almost one half of RCC metastases. Thus, fascin may be a promising molecular target for future cancer therapy.
    Tipo de documento:
    Referencia
    Referencia del producto:
    MAB3582
    Nombre del producto:
    Anti-Fascin Antibody, clone 55K2

  • Diversity in the neural circuitry of cold sensing revealed by genetic axonal labeling of transient receptor potential melastatin 8 neurons. 18094254

    Sensory nerves detect an extensive array of somatosensory stimuli, including environmental temperatures. Despite activating only a small cohort of sensory neurons, cold temperatures generate a variety of distinct sensations that range from pleasantly cool to painfully aching, prickling, and burning. Psychophysical and functional data show that cold responses are mediated by both C- and A delta-fibers with separate peripheral receptive zones, each of which likely provides one or more of these distinct cold sensations. With this diversity in the neural basis for cold, it is remarkable that the majority of cold responses in vivo are dependent on the cold and menthol receptor transient receptor potential melastatin 8 (TRPM8). TRPM8-null mice are deficient in temperature discrimination, detection of noxious cold temperatures, injury-evoked hypersensitivity to cold, and nocifensive responses to cooling compounds. To determine how TRPM8 plays such a critical yet diverse role in cold signaling, we generated mice expressing a genetically encoded axonal tracer in TRPM8 neurons. Based on tracer expression, we show that TRPM8 neurons bear the neurochemical hallmarks of both C- and A delta-fibers, and presumptive nociceptors and non-nociceptors. More strikingly, TRPM8 axons diffusely innervate the skin and oral cavity, terminating in peripheral zones that contain nerve endings mediating distinct perceptions of innocuous cool, noxious cold, and first- and second-cold pain. These results further demonstrate that the peripheral neural circuitry of cold sensing is cellularly and anatomically complex, yet suggests that cold fibers, caused by the diverse neuronal context of TRPM8 expression, use a single molecular sensor to convey a wide range of cold sensations.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo

  • Development, characterization, and applications of a novel estrogen receptor beta monoclonal antibody. 22095450

    The role of estrogen receptor alpha (ERα) in breast cancer has been studied extensively, and its protein expression is prognostic and a primary determinant of endocrine sensitivity. However, much less is known about the role of ERβ and its relevance remains unclear due to the publication of conflicting reports. Here, we provide evidence that much of this controversy may be explained by variability in antibody sensitivity and specificity and describe the development, characterization, and potential applications of a novel monoclonal antibody targeting full-length human ERβ and its splice variant forms. Specifically, we demonstrate that a number of commercially available ERβ antibodies are insensitive for ERβ and exhibit significant cross-reaction with ERα. However, our newly developed MC10 ERβ antibody is shown to be highly specific and sensitive for detection of full-length ERβ and its variant forms. Strong and variable staining patterns for endogenous levels of ERβ protein were detected in normal human tissues and breast tumors using the MC10 antibody. Importantly, ERβ was shown to be expressed in a limited cohort of both ERα positive and ERα negative breast tumors. Taken together, these data demonstrate that the use of poorly validated ERβ antibodies is likely to explain much of the controversy in the field with regard to the biological relevance of ERβ in breast cancer. The use of the MC10 antibody, in combination with highly specific antibodies targeting only full-length ERβ, is likely to provide additional discriminatory features in breast cancers that may be useful in predicting response to therapy.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB1410
    Nombre del producto:
    Anti-Estrogen Receptor β Antibody, human ER-β

  • Increased oxidative properties of gastrocnemius in rats fed on a high-protein diet. 17509855

    It has been reported that a high-protein diet containing 30% protein partially prevents skeletal muscle fiber type changes (slow to fast) under atrophic conditions. No studies have examined the detailed effects of dietary protein on the oxidative properties of skeletal muscles. We examined the effects of a high-protein diet on the oxidative properties of rat gastrocnemius. Nineteen male Wistar rats (5 weeks old) were divided into the following groups: (1) control diet [15% protein (15P); n=6], (2) 25% protein (25P; n=6) and (3) 35% protein (35P, n=7). After 4 weeks of feeding, succinate dehydrogenase (SDH) staining and myosin isoforms were analyzed, along with the expression of the major transcription-related molecules for fast-to-slow fiber transition, i.e., peroxisome proliferator-activated receptor gamma coactivator (PGC) 1 alpha and nuclear factor of activated T cells (NFAT) c1. SDH staining showed that the relative oxidative fiber content of the 35P group was significantly higher than that of the 15P group. The slow myosin heavy chain content in the 35P group was also higher than that in the 15P group. Western blotting analysis showed that the gastrocnemius of the 35P group contained significantly higher amounts of PGC1 alpha and NFATc1 than that of the 15P group. We conclude that a high-protein diet, i.e., 35% protein, induces oxidative properties in rat gastrocnemius.
    Tipo de documento:
    Referencia
    Referencia del producto:
    AB3242
    Nombre del producto:
    Anti-PGC-1 Antibody

  • Identification of upstream cis-acting regulatory elements controlling lineage-specific expression of the mouse NK cell activation receptor, NKR-P1C. 12813047

    Mouse NKR-P1C (NK1.1) is a homodimeric type II transmembrane protein expressed on natural killer (NK) cells, NKT cells, and on CD117+ progenitor thymocytes capable of giving rise to cells of the T and NK lineages. Although its physiological ligands remain unknown, NKR-P1C engagement with a monoclonal antibody (mAb) leads to interferon-gamma (IFN-gamma) production and the directed release of cytotoxic granules from NK cells. We have cloned and sequenced a approximately 10-kb genomic fragment corresponding to the 5'-flanking region of the C57Bl/6 mouse NKR-P1C gene. A transcriptional initiation site has been mapped in NK cells and an NK1.1+ T cell line by primer extension and rapid amplification of 5'-cDNA ends (5'-RACE) techniques. Although the 5'-flanking region of NKR-P1C is TATA-less, we have identified an initiator region and a downstream promoter element, which together constitute the principal minimal functional promoter. Computational analysis of the 10-kb 5'-flanking region revealed potential regulatory factor binding sites. DNaseI hypersensitivity assays identified a single hypersensitive site (HS) about a 9-kb upstream of the transcriptional initiation site. This site, termed HS1, was able to act as a transcriptional enhancer element in an NK cell line, while minimally affecting transcription in non-NK cell lines. Moreover, the HS1 element was shown to function as a promoter, with a transcript detected only in fetal NK1.1+ cells. An additional promoter and two non-coding exons were also characterized. These results identify the minimal upstream cis-acting elements, and point to a complex regulatory mechanism involved in the lineage-specific control of NKR-P1C expression in NK lymphocytes.
    Tipo de documento:
    Referencia
    Referencia del producto:
    ECM600
    Nombre del producto:
    uPA Activity Assay Kit

  • Development of a mouse monoclonal antibody for the detection of asymmetric dimethylarginine of Translocated in LipoSarcoma/FUsed in Sarcoma and its application in analyzi ... 25810899

    RNA-binding protein Translocated in LipoSarcoma/FUsed Sarcoma (TLS/FUS) is one of causative genes for familial amyotrophic lateral sclerosis (ALS). We previously identified that TLS was associated with protein arginine methyltransferase 1 (PRMT1), and four arginine residues within TLS (R216, R218, R242 and R394) were consistently dimethylated. Protein arginine methylation is involved in various cellular events such as signal transduction, transcriptional regulation and protein-protein interactions.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo

  • Digital microfluidic assay for protein detection. 24449893

    Global studies of the human proteome have revealed a plethora of putative protein biomarkers. However, their application for early disease detection remains at a standstill without suitable methods to realize their utility in the clinical setting. There thus continues to be tremendous interest in developing new technology for sensitive protein detection that is both low in cost and carries a small footprint to be able to be used at the point of care. The current gold standard method for protein biomarker detection is the ELISA, which measures protein abundance using bulky fluorescent scanners that lack portability. Here, we present a digital microfluidic platform for protein biomarker detection that is low in cost compared with standard optical detection methods, without any compromise in sensitivity. This platform furthermore makes use of simple electronics, enabling its translation into a portable handheld device, and has been developed in a manner that can easily be adapted to assay different types of proteomic biomarkers. We demonstrate its utility in quantifying not only protein abundance, but also activity. Interleukin-6 abundance could be assayed from concentrations as low as 50 pM (an order of magnitude lower than that detectable by a comparable laboratory designed ELISA) using less than 5 μL of sample, and Abelson tyrosine kinase activity was detectable in samples containing 100 pM of kinase.
    Tipo de documento:
    Referencia
    Referencia del producto:
    05-1050
    Nombre del producto:
    4G10® Platinum, Anti-Phosphotyrosine Antibody (mouse monoclonal cocktail IgG2b)

  • Expression of a protein involved in bone resorption, Dkk1, is activated by HTLV-1 bZIP factor through its activation domain. 20653953

    Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia, a malignancy characterized by uncontrolled proliferation of virally-infected CD4+ T-cells. Hypercalcemia and bone lesions due to osteoclast-mediated bone resorption are frequently associated with more aggressive forms of the disease. The HTLV-1 provirus contains a unique antisense gene that expresses HTLV-1 basic leucine zipper (bZIP) factor (HBZ). HBZ is localized to the nucleus where it regulates levels of transcription by binding to certain cellular transcriptional regulators. Among its protein targets, HBZ forms a stable complex with the homologous cellular coactivators, p300 and CBP, which is modulated through two N-terminal LXXLL motifs in the viral protein and the conserved KIX domain in the coactivators.To determine the effects of these interactions on transcription, we performed a preliminary microarray analysis, comparing levels of gene expression in cells with wild-type HBZ versus cells with HBZ mutated in its LXXLL motifs. DKK1, which encodes the secreted Wnt signaling inhibitor, Dickkopf-1 (Dkk1), was confirmed to be transcriptionally activated by HBZ, but not its mutant. Dkk1 plays a major role in the development of bone lesions caused by multiple myeloma. In parallel with the initial findings, activation of Dkk1 expression by HBZ was abrogated by siRNA-mediated knockdown of p300/CBP or by a truncated form of p300 containing the KIX domain. Among HTLV-1-infected T-cell lines tested, the detection of Dkk1 mRNA partially correlated with a threshold level of HBZ mRNA. In addition, an uninfected and an HTLV-1-infected T-cell line transfected with an HBZ expression vector exhibited de novo and increased DKK1 transcription, respectively. In contrast to HBZ, The HTLV-1 Tax protein repressed Dkk1 expression.These data indicate that HBZ activates Dkk1 expression through its interaction with p300/CBP. However, this effect is limited in HTLV-1-infected T-cell lines, which in part, may be due to suppression of Dkk1 expression by Tax. Consequently, the ability of HBZ to regulate expression of Dkk1 and possibly other cellular genes may only be significant during late stages of ATL, when Tax expression is repressed.
    Tipo de documento:
    Referencia
    Referencia del producto:
    Múltiplo
    Nombre del producto:
    Múltiplo