gebhart/patrepeval huggingface dataset:
Modulation of murine tumor growth and colonization by bromelaine, an extract of the pineapple plant (Ananas comosum L.). (2005)

The antitumor and antimetastatic activities of the plant cysteine endoproteinase bromelaine were evaluated in a murine model. Syngeneic sarcoma L-1 cells were incubated with bromelaine (after preceeding time and dosage kinetics) and subcutaneously; (s.c.) or intravenously; (i.v.) inoculated into BALB/c-mice (n = 5 per experimental group) to induce local tumor growth or lung colonization. Compared to non-protease incubated L-1 cells, local tumor growth and experimental lung metastasis decreased significantly (p < 0.05). After bromelaine incubation of the tumor cells. Sarcoma L-1 cells induced local tumor growth after s.c. inoculation and lung colonization after i.v. injection. Intraperitoneal (i.p.) or s.c. administration of bromelaine (optimal dosage and time schedule tested in preceeding kinetic studies) significantly (p < 0.05) reduced local tumor weight, however, lung colonization was non-significantly reduced. Bromelaine incubation of sarcoma L-1 cells significantly reduced their tumorigenic/metastatic capacities. Bromelaine treatment after tumor cell inoculation significantly reduced local tumor growth, experimental lung metastasis, however, to a lesser, non-significant degree.
Crystal structure of truncated human apolipoprotein A-I suggests a lipid-bound conformation (1997)

The structure of truncated human apolipoprotein A-I (apo A-I), the major protein component of high density lipoprotein, has been determined at 4-A resolution. The crystals comprise residues 44-243 (exon 4) of apo A-I, a fragment that binds to lipid similarly to intact apo A-I and that retains the lipid-bound conformation even in the absence of lipid. The molecule consists almost entirely of a pseudo-continuous, amphipathic alpha-helix that is punctuated by kinks at regularly spaced proline residues; it adopts a shape similar to a horseshoe of dimensions 125 x 80 x 40 A. Four molecules in the asymmetric unit associate via their hydrophobic faces to form an antiparallel four-helix bundle with an elliptical ring shape. Based on this structure, we propose a model for the structure of apo A-I bound to high density lipoprotein.
ACTIBIND, an actin‐binding fungal T2‐RNase with antiangiogenic and anticarcinogenic characteristics (2006)

This study indicated that ACTIBIND is an effective antiangiogenic and anticarcinogenic factor.
Probing structure and function of the raf protein kinase domain with monoclonal antibodies. (1990)

Five monoclonal antibodies were generated against the raf kinase domain. All antibodies react with different isozymes of the raf family, as well as Raf proteins from different species, albeit with differential affinities. Epitope mapping showed all five epitopes clustered in the vicinity of the conserved APE sequence. Although thought to be an essential part of the catalytic site, antibody binding to that domain does not affect kinase activity in vitro or the capability to specifically associate with other cellular proteins. Based on a detailed dissection of the epitopes, a comparative analysis of secondary structure predictions indicates a common structural motif in that region, which is highly conserved amongst protein kinases of the serine/threonine as well as the tyrosine class.
Synthesis of Potential Anticancer Agents. VI.2 Use of O-Benzoyl Blocking Group for Synthesis of 6-Chloropurine Nucleosides (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Potential Anticancer Agents. VI.2 Use of O-Benzoyl Blocking Group for Synthesis of 6-Chloropurine NucleosidesB. R. BAKER, KATHLEEN HEWSON, H. JEANETTE THOMAS, and JAMES A. JOHNSON Jr.Cite this: J. Org. Chem. 1957, 22, 8, 954–959Publication Date (Print):August 1, 1957Publication History Published online1 May 2002Published inissue 1 August 1957https://pubs.acs.org/doi/10.1021/jo01359a027https://doi.org/10.1021/jo01359a027research-articleACS PublicationsRequest reuse permissionsArticle Views176Altmetric-Citations21LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Risks to the Fetus of Anticoagulant Therapy During Pregnancy (1989)

The use of anticoagulants during pregnancy is problematic because of the potential adverse effects to the mother and the fetus. Heparin does not cross the placenta, and thus, it was surprising that a recent report concluded that heparin therapy during pregnancy was as risky as oral anticoagulant therapy. Therefore, we performed a literature review of fetal/infant outcomes following anticoagulant therapy during pregnancy. We examined 186 reports which described fetal/infant outcomes in 1,325 pregnancies associated with anticoagulant therapy. The rates of adverse fetal/infant outcomes including death, prematurity and cogenital malformations following treatment with heparin, oral anticoagulants, or both were calculated. The previously described high rate of adverse fetal/infant outcomes with heparin-treated patients, could be accounted for by the frequent use of heparin in pregnancies with comorbid conditions independently associated with adverse outcomes and by reports of uncomplicated prematurity. After excluding such pregnancies, outcomes in heparin-treated patients are similar to the normal population.
Circulating Th1 and Th2 cytokines in patients with hepatitis C virus infection (1998)

The imbalance of T-helper (Th) lymphocyte cytokine production may play an important role in immunopathogenesis of persistent hepatitis C virus (HCV) infection. To know whether an imbalance between Th1 and Th2 cytokines is present in chronic HCV infection, serum levels of Th1 cytokines, interferon gamma (IFN-gamma) and interleukin (IL)-2, and Th2 cytokines, IL-4 and IL-10, were measured using enzyme-linked immunosorbent assay in this study. Eighteen individuals with chronic HCV infection, 11 healthy subjects as normal controls and 10 chronic HBV infected patients as disease controls were observed. The results showed that the levels of Th2 cytokines (IL-4 and IL-10) were significantly increased in chronic HCV infected patients compared with normal controls (IL-4: 30.49+/-17.55 vs. 14.94+/-13.73, pg/ml, P<0.025; IL-10: 50.30+/-19.59 vs. 17.87+/-9.49, pg/ml, P<0.001). Similarly, the levels of Th1 cytokine, IL-2, was also elevated in individuals with chronic HCV infection when compared with normal controls (IL-2: 118.53+/-95.23 vs. 61.57+/-28.70, pg/ml, P<0.05). However, Th1 cytokine IFN-gamma level was not significantly changed during HCV infection (IFN-gamma: 28.09+/-15.65 vs. 24.10+/-15.61, pg/ml, P>0.05). Furthermore, the elevated levels of Th2 cytokines are greater than Th1 cytokines in HCV infection. Thus, the study indicates that an enhanced Th2 responses are present during chronic HCV infection, which may partly be responsible for the persistence of HCV infection.
Radiation-induced degradation of D-glucose in anaerobic condition. (1977)

Gamma-radiolosis of D-glucose in aqueous solution under anaerobic condition was investigated. D-Glucose was significantly decomposed by action of a hydroxyl radical, a primary radiolytic product of water. Under anaerobic condition, glucose radicals formed by hydrogen abstraction of hydroxyl radical were dehydrated to give deoxygenated sugars, and a part of the radicals followed disproportionation reaction to afford dicarbonyl sugars. Among the products formed through these reactions, 2-deoxy-D-arabinohexono-1, 4-lactone (G in N2=0.6, G in N2O=0.8), 3-deoxy-D-erythrohexosulose and other 3-deoxy sugars as deoxygenated compounds, and D-arabinohexosulose and D-xylohexos-5-ulose as dicarbonyl compounds were identified. From these results, the radiolytic scheme of D-glucose in the absence of oxygen was proposed.
Label-free photoacoustic nanoscopy (2014)

Super-resolution microscopy techniques - capable of overcoming the diffraction limit of light - have opened new opportunities to explore subcellular structures and dynamics not resolvable in conventional far-field microscopy. However, relying on staining with exogenous fluorescent markers, these techniques can sometimes introduce undesired artifacts to the image, mainly due to large tagging agent sizes and insufficient or variable labeling densities. By contrast, the use of endogenous pigments allows imaging of the intrinsic structures of biological samples with unaltered molecular constituents. Here, we report label-free photoacoustic (PA) nanoscopy, which is exquisitely sensitive to optical absorption, with an 88 nm resolution. At each scanning position, multiple PA signals are successively excited with increasing laser pulse energy. Because of optical saturation or nonlinear thermal expansion, the PA amplitude depends on the nonlinear incident optical fluence. The high-order dependence, quantified by polynomial fitting, provides super-resolution imaging with optical sectioning. PA nanoscopy is capable of super-resolution imaging of either fluorescent or nonfluorescent molecules.
Clinical Relevance of KRAS in Human Cancers (2010)

The KRAS gene (Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) is an oncogene that encodes a small GTPase transductor protein called KRAS. KRAS is involved in the regulation of cell division as a result of its ability to relay external signals to the cell nucleus. Activating mutations in the KRAS gene impair the ability of the KRAS protein to switch between active and inactive states, leading to cell transformation and increased resistance to chemotherapy and biological therapies targeting epidermal growth factor receptors. This review highlights some of the features of the KRAS gene and the KRAS protein and summarizes current knowledge of the mechanism of KRAS gene regulation. It also underlines the importance of activating mutations in the KRAS gene in relation to carcinogenesis and their importance as diagnostic biomarkers, providing clues regarding human cancer patients' prognosis and indicating potential therapeutic approaches.
Convergent temporal dynamics of the human infant gut microbiota (2009)

Temporal dynamics of the human gut microbiota is of fundamental importance for the development of proper gut function and maturation of the immune system. Here we present a description of infant gut ecological dynamics using a combination of nonlinear data modeling and simulations of the early infant gut colonization processes. Principal component analysis of infant microbiota 16S rRNA gene microarray data showed that the main directions of variation were defined by three phylum-specific probes targeting Bacteroides, Proteobacteria and Firmicutes. Nonlinear regression analysis identified several dynamic interactions between these three phyla. Simulations of the early phylum-level colonization process showed the relatively rapid establishment of an equilibrium community after an unstable initial phase. In general, varying the initial composition of phyla in the simulations had little bearing on the final equilibrium. The dynamic interaction model was found to maintain its predictive ability for Proteobacteria and Firmicutes well into the simulation, whereas Bacteroides densities tended to be underestimated, possibly due to host top-down selection for Bacteroides. In accordance with our model, initial perturbation of the microbiota by different mode of delivery (vaginal and C-section) did not affect the later phylum composition in the infants investigated. Considering the predictive ability and convergence of our phylum-level model, we now propose that deterministic bacterial-bacterial interactions are more important for shaping the human infant gut microbiota than previously anticipated.
Chaperonin Function: Folding by Forced Unfolding (1999)

The ability of the GroEL chaperonin to unfold a protein trapped in a misfolded condition was detected and studied by hydrogen exchange. The GroEL-induced unfolding of its substrate protein is only partial, requires the complete chaperonin system, and is accomplished within the 13 seconds required for a single system turnover. The binding of nucleoside triphosphate provides the energy for a single unfolding event; multiple turnovers require adenosine triphosphate hydrolysis. The substrate protein is released on each turnover even if it has not yet refolded to the native state. These results suggest that GroEL helps partly folded but blocked proteins to fold by causing them first to partially unfold. The structure of GroEL seems well suited to generate the nonspecific mechanical stretching force required for forceful protein unfolding.
Large-scale production and purification of functional recombinant bovine rhodopsin with the use of the baculovirus expression system (1999)

Here we describe a generic procedure for the expression and purification of milligram quantities of functional recombinant eukaryotic integral membrane proteins, exemplified by hexahistidine-tagged bovine rhodopsin. These quantities were obtained with the recombinant baculovirus/Sf9 insect cell-based expression system in large-scale bioreactor cultures with the use of a serum-free and protein-free growth medium. After optimization procedures, expression levels up to 4 mg/l were established. The recombinant rhodopsin could be purified with high overall yield by using immobilized-metal-affinity chromatography on Ni(2+)-agarose. After reconstitution into a native lipid environment, the purified protein was functionally indistinguishable from native rhodopsin with regard to the following parameters: spectral absorbance band, structural changes after photoactivation, and G-protein activation. The procedures developed can be adapted to other membrane proteins. The ability to produce and purify tens of milligrams of functional recombinant eukaryotic membrane protein meets the ever-increasing demand of material necessary to perform detailed biochemical and structural biophysical studies that are essential in unravelling their working mechanism at a molecular level.
(TRANS)GENE SILENCING IN PLANTS: How Many Mechanisms? (2000)

Epigenetic silencing of transgenes and endogenous genes can occur at the transcriptional level (TGS) or at the posttranscriptional level (PTGS). Because they can be induced by transgenes and viruses, TGS and PTGS probably reflect alternative (although not exclusive) responses to two important stress factors that the plant's genome has to face: the stable integration of additional DNA into chromosomes and the extrachromosomal replication of a viral genome. TGS, which results from the impairment of transcription initiation through methylation and/or chromatin condensation, could derive from the mechanisms by which transposed copies of mobile elements and T-DNA insertions are tamed. PTGS, which results from the degradation of mRNA when aberrant sense, antisense, or double-stranded forms of RNA are produced, could derive from the process of recovery by which cells eliminate pathogens (RNA viruses) or their undesirable products (RNA encoded by DNA viruses). Mechanisms involving DNA-DNA, DNA-RNA, or RNA-RNA interactions are discussed to explain the various pathways for triggering (trans)gene silencing in plants.
Activin/Nodal and FGF pathways cooperate to maintain pluripotency of human embryonic stem cells (2005)

Maintenance of pluripotency is crucial to the mammalian embryo's ability to generate the extra-embryonic and embryonic tissues that are needed for intrauterine survival and foetal development. The recent establishment of embryonic stem cells from human blastocysts (hESCs) provides an opportunity to identify the factors supporting pluripotency at early stages of human development. Using this in vitro model, we have recently shown that Nodal can block neuronal differentiation, suggesting that TGFbeta family members are involved in cell fate decisions of hESCs, including preservation of their pluripotency. Here, we report that Activin/Nodal signalling through Smad2/3 activation is necessary to maintain the pluripotent status of hESCs. Inhibition of Activin/Nodal signalling by follistatin and by overexpression of Lefty or Cerberus-Short, or by the Activin receptor inhibitor SB431542, precipitates hESC differentiation. Nevertheless, neither Nodal nor Activin is sufficient to sustain long-term hESC growth in a chemically defined medium without serum. Recent studies have shown that FGF2 can also maintain long-term expression of pluripotency markers, and we find that inhibition of the FGF signalling pathway by the tyrosine kinase inhibitor SU5402 causes hESC differentiation. However, this effect of FGF on hESC pluripotency depends on Activin/Nodal signalling, because it is blocked by SB431542. Finally, long-term maintenance of in-vitro pluripotency can be achieved with a combination of Activin or Nodal plus FGF2 in the absence of feeder-cell layers, conditioned medium or Serum Replacer. These findings suggest that the Activin/Nodal pathway maintains pluripotency through mechanism(s) in which FGF acts as a competence factor and therefore provide further evidence of distinct mechanisms for preservation of pluripotency in mouse and human ESCs.
An exonuclease-amplification coupled capture technique improves detection of PCR product (1993)

Journal Article An exonuclease-amplification coupled capture technique improves detection of PCR product Get access Brian Holloway, Brian Holloway 1Centers for Disease Control and Prevention, National Center for Infectious DiseasesAtlanta, GA, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Dean D. Erdman, Dean D. Erdman 1Centers for Disease Control and Prevention, National Center for Infectious DiseasesAtlanta, GA, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Edison L. Durigon, Edison L. Durigon 1Centers for Disease Control and Prevention, National Center for Infectious DiseasesAtlanta, GA, USA2University of Sao Paulo, Institute of Biomedical SciencesSao Paulo, Brazil Search for other works by this author on: Oxford Academic PubMed Google Scholar James J. Murtagh, Jr James J. Murtagh, Jr 3Emory University, Pulmonary and Critical Care MedicineAtlanta VA Medical Center, Decatur, GA, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 21, Issue 16, 11 August 1993, Pages 3905, https://doi.org/10.1093/nar/21.16.3905 Published: 11 August 1993 Article history Received: 09 June 1993 Accepted: 28 June 1993 Published: 11 August 1993
PPARγ signaling exacerbates mammary gland tumor development (2004)

Breast cancer cell lines that express the nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) can be prompted to undergo growth arrest and differentiation when treated with synthetic PPAR gamma ligands. To evaluate the therapeutic potential of increased PPAR gamma signaling in vivo, we generated transgenic mice that express a constitutively active form of PPAR gamma in mammary gland. These mice are indistinguishable from their wild-type littermates. However, when bred to a transgenic strain prone to mammary gland cancer, bigenic animals develop tumors with greatly accelerated kinetics. Surprisingly, in spite of their more malignant nature, bigenic tumors are more secretory and differentiated. The molecular basis of this tumor-promoting effect may be an increase in Wnt signaling, as ligand activation of PPAR gamma potentiates Wnt function in an in vivo model of this pathway. These results suggest that once an initiating event has taken place, increased PPAR gamma signaling serves as a tumor promoter in the mammary gland.
Anaplastic lymphoma kinase fusions: Roles in cancer and therapeutic perspectives (Review) (2018)

Receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK) serves a crucial role in brain development. <i>ALK</i> is located on the short arm of chromosome 2 (2p23) and exchange of chromosomal segments with other genes, including nucleophosmin (<i>NPM</i>), echinoderm microtubule-associated protein-like 4 (<i>EML4</i>) and <i>Trk</i>-fused gene (<i>TFG</i>), readily occurs. Such chromosomal translocation results in the formation of chimeric <i>X-ALK</i> fusion oncoproteins, which possess potential oncogenic functions due to constitutive activation of ALK kinase. These proteins contribute to the pathogenesis of various hematological malignancies and solid tumors, including lymphoma, lung cancer, inflammatory myofibroblastic tumors (IMTs), Spitz tumors, renal carcinoma, thyroid cancer, digestive tract cancer, breast cancer, leukemia and ovarian carcinoma. Targeting of ALK fusion oncoproteins exclusively, or in combination with ALK kinase inhibitors including crizotinib, is the most common therapeutic strategy. As is often the case for small-molecule tyrosine kinase inhibitors (TKIs), drug resistance eventually develops via an adaptive secondary mutation in the <i>ALK</i> fusion oncogene, or through engagement of alternative signaling mechanisms. The updated mechanisms of a variety of <i>ALK</i> fusions in tumorigenesis, proliferation and metastasis, in addition to targeted therapies are discussed below.
Amyloid‐beta reduction by memapsin 2 (beta‐secretase) immunization (2007)

Memapsin 2 (beta-secretase, BACE1) is the protease that initiates cleavage of beta-amyloid precursor protein leading to the production of amyloid-beta (Abeta) and the onset of Alzheimer's disease (AD). Reducing Abeta by targeting memapsin 2 is a major strategy in developing new AD therapy. Here, in a proof-of-concept study, we show that immunization of transgenic AD mice (Tg2576) with memapsin 2 resulted in Abeta reduction and cognitive improvement. To study the basis of this therapy, we demonstrated that anti-memapsin 2 (anti-M2) antibodies were rapidly internalized and reduced Abeta production in cultured cells. These antibodies also effectively crossed the blood-brain barrier to reach the brain. Two- and 10-month Tg2576 mice were immunized and monitored over 10 and 6 months, respectively. We observed a significant decrease of plasma and brain Abeta40 and Abeta42 (approximately 35%) in the immunized mice as compared to controls. Immunized mice also showed better cognitive performance than controls in both cohorts. Brain histological analyses found no evidence of T cell/microglia/astrocyte activation in the immunized mice, suggesting the absence of inflammatory responses. These results suggest that memapsin 2 immunization in Tg2576 was effective in reducing Abeta production and improving cognitive function and that the current approach warrants further investigation as a therapy for AD.
Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain Injury Dynamics: A Systematic Review (2017)

Serial sampling of brain-specific proteins in serum reveals different temporal trajectories that should be acknowledged. Proteins with shorter serum availability, like S100B, may be superior to proteins such as NF-L in detection of secondary harmful events when monitoring patients with TBI.