gebhart/patrepeval huggingface dataset:
Glucocorticoids induce a G1/G0 cell cycle arrest of Con8 rat mammary tumor cells that is synchronously reversed by steroid withdrawal or addition of transforming growth factor-alpha. (1993)

Con8 mammary tumor cells are an epithelial cell line derived from the 7,12-dimethylbenz(alpha)anthracene-induced 13762NF rat mammary adenocarcinoma. The synthetic glucocorticoid dexamethasone suppresses the growth of Con8 cells, and after 5 days of treatment with this steroid, Con8 cells undergo less than 0.5 population doublings. This growth arrest is accompanied by a 30-fold elevation in c-jun transcript levels, no change in c-fos expression, and a moderate increase in total AP-1 transcriptional activity. Dexamethasone inhibited DNA synthesis within one cell cycle, and flow cytometry of propidium iodide-stained nuclei demonstrated that dexamethasone growth-suppressed cells had a DNA content indicative of a specific cell cycle block in either G1 or G0. Consistent with a G1/G0 arrest of the cell cycle, dexamethasone did not prevent Con8 cells from entering the S phase after release from synchronization at the G1/S boundary by a double thymidine block. Analysis of [3H]thymidine incorporation and autoradiography of [3H]thymidine-labeled nuclei revealed that after either dexamethasone withdrawal or the addition of transforming growth factor-alpha (TGF alpha), Con8 cells synchronously reinitiate cell cycle progression. Northern blot analysis demonstrated that an induction of transcripts for the G1 marker genes c-myc and cyclin D1 occurs before cells enter the S-phase. After dexamethasone withdrawal, c-myc and cyclin D1 expression transiently peak at 2 and 4 h, respectively. In contrast, c-myc expression peaked at 0.5-1 h, whereas cyclin D1 expression was induced at 2 h and maintained at a high level after the addition of TGF alpha. Our results demonstrate that glucocorticoids induce a specific block of the cell cycle progression of a rat mammary tumor cell, and that after synchronous progression through the cell cycle, the temporal expression pattern for c-myc and cyclin D1 is distinct for dexamethasone release vs. the addition of TGF alpha to glucocorticoid-suppressed cells.
Proteins in Action Monitored by Time‐Resolved FTIR Spectroscopy (2005)

In the post genome era proteins coming into the focus of life sciences. X-ray structure analysis and NMR spectroscopy are established methods to determine the geometry of proteins. In order to determine the molecular reaction mechanism of proteins, time-resolved FTIR (trFTIR) difference spectroscopy emerges as a valuable tool. In this Minireview we describe the trFTIR difference spectroscopy and show its application on the light-driven proton pump bacteriorhodopsin (bR), the photosynthetic reaction center and the GTPase Ras, which is crucial in signal transduction. The main principles of the technique are presented, including a summary of triggering techniques, scan modes and analysis.
Diffusible factors from the murine cell line M2-10B4 support human in vitro hematopoiesis. (1994)

Significantly more primitive human hematopoietic progenitors are maintained and differentiate when cultured separately from the stroma by a microporous membrane ("stroma-noncontact" cultures) than when cultured in direct contact with stromal layers ("stroma-contact" cultures). This suggests that diffusible stroma-derived factors may be sufficient for the in vitro induction of progenitor proliferation and differentiation. To further characterize stroma-derived factors that maintain long-term bone marrow culture initiating cells (LTBMC-IC), we compared the hematopoietic supportive capacity of human marrow stroma with that of the murine marrow stroma-derived fibroblast cell line M2-10B4 as well as two embryonic fibroblast cell lines, the human FHS-173-WE and the murine NIH-3T3 cell lines. We demonstrate that LTBMC-IC, present in human CD34+/HLA-DR- (DR- cells), are maintained equally well and give rise to similar numbers of committed progenitors, that is--colony-forming cells (CFC)--when cultured in contact with human marrow stroma or any cell line feeder (stroma-contact cultures). LTBMC-IC, cultured in marrow stroma or M2-10B4 stroma-noncontact cultures, were maintained significantly better and gave rise to significantly more CFC than when cultured in human marrow stroma or M2-10B4 contact cultures. However, LTBMC-IC maintenance and differentiation in FHS-173-WE or NIH-3T3 noncontact cultures was significantly less than in human marrow stroma or M2-10B4 noncontact cultures. These studies indicate that systematic comparison of diffusible growth stimulatory factors in conditioned media from M2-10B4 cells and FHS-173-WE may lead to the characterization of growth regulatory factors required for in vitro maintenance and differentiation of human primitive LTBMC-IC. Since diffusible factors from the M2-10B4 cell line can support human hematopoiesis, our observations may also have important implications for in vitro stem cell expansion protocols.
Gene Transfer and Molecular Cloning of the Human NGF Receptor (1986)

Nerve growth factor (NGF) and its receptor are important in the development of cells derived from the neural crest. Mouse L cell transformants have been generated that stably express the human NGF receptor gene transfer with total human DNA. Affinity cross-linking, metabolic labeling and immunoprecipitation, and equilibrium binding with 125I-labeled NGF revealed that this NGF receptor had the same size and binding characteristics as the receptor from human melanoma cells and rat PC12 cells. The sequences encoding the NGF receptor were molecularly cloned using the human Alu repetitive sequence as a probe. A cosmid clone that contained the human NGF receptor gene allowed efficient transfection and expression of the receptor.
The metabolic spectrum of halofenate. (1975)

Halofenate is a new antilipemic drug which is an ester of carboxylic acid. In dosages ranging from 10 to 15 mg/kg, halofenate produces prominent decreases in serum triglycerides and uric acid, with only a slight reduction in serum cholesterol. The decrease in serum uric acid is due to augumented uricosuria. Halofenate is less antilipemic, but more antiuricemic than clofibrate. It apparently interferes with the protein binding of some hormones (thyroid) and drugs (tolbutamide), which can produce changes in the laboratory or clinical findings. In general, halofenate was well tolerated, except for occasional gastrointestinal symptoms.
Strategies for antigen loading of dendritic cells to enhance the antitumor immune response. (2002)

Dendritic cells (DCs) primed with tumor antigens can effectively mediate the regression of a variety of established solid malignancies in both murine and human models. Despite such clinical efficacy, the optimal means of DC priming is unknown. The goal of this study was to compare three methods of tumor preparation: irradiation, boiling, or freeze thaw lysis for DC priming. Mouse bone marrow-derived DCs were loaded with defined ratios of E.G7 tumor cells expressing a model tumor antigen, OVA. Sensitized DCs were used for stimulation of OVA-specific CTLs derived from OT-1 T-cell receptor transgenic mice. IFN-gamma release, determined by ELISA at 24 and 48 h, was used to assess the expression of antigens by DCs. DCs loaded with irradiated tumors were effective stimulators for OT-1 CTLs, whereas DCs stimulated with freeze-thawed or boiled tumors did not stimulate IFN-gamma production. Freeze-thaw lysis appeared to inhibit CTL activity in vitro and in two of three cases, this effect was not overcome by the addition of OVA. The ability to load irradiated tumor cells was reproduced in two analogous human melanoma models using melanoma cell lines expressing gp100 and CTL clones specific for a gp100 melanoma antigen. Consistent with the in vitro data, only DC/irradiated tumor vaccines were effective in preventing or delaying outgrowth of E.G7 and a poorly immunogenic murine squamous cell carcinoma (SCCVII), on local tumor challenge. These data demonstrate that the method of tumor cell preparation clearly influences the ability of DCs to present antigen to T cells. Correlation of in vitro data with the generation of protective immunity in vivo suggests the utility of irradiated tumor-primed DCs as a means to generate protective immunity in patients with solid malignancies.
Gamma and Ultraviolet Radiation Cause DNA Crosslinking in the Presence of Metal Ions at High pH¶ (2001)

M-DNA is a novel duplex conformation in which metal ions such as Co2+, Ni2+ or Zn2+ replace the imino protons of every base pair. An ethidium fluorescence assay was used to estimate lesions in M-DNA induced by gamma- and UV radiation. General damage to DNA was assessed from the loss of ethidium fluorescence after irradiation of calf thymus DNA. Crosslinks were measured from the return of ethidium fluorescence after a heating and cooling step. Strand breaks were estimated from the loss of fluorescence in covalently closed circular plasmid DNA after a heating and cooling step. For the Co2+ form of M-DNA, gamma-radiation caused the very efficient formation of crosslinks which was not observed with B-DNA nor with the Ni2+ or Zn2+ forms of M-DNA. The crosslinks occurred in both A-T and G-C base pairs but did not form in the presence of a free radical scavenger. Crosslinks induced by UV radiation also formed at a faster rate in the Co2+, Ni2+ and Zn2+ forms of M-DNA compared to B-DNA; crosslinking occurred in all DNA but was more prominent in AT-rich sequences and was not inhibited by a free radical scavenger. Therefore, the presence of certain metal ions may lead to large increases in the formation of radiation-induced crosslinks in DNA.
CERVICAL CANCER PREVENTION (1998)

Public Health Institute, Berkeley, CA, USA, and M Fuentes-Vega, Merced Public Health Department, Merced, CA USA
Functional expression of zeaxanthin glucosyltransferase from Erwinia herbicola and a proposed uridine diphosphate binding site. (1992)

Erwinia herbicola, a nonphotosynthetic bacterium, is yellow colored due to the accumulation of unusually polar carotenoids, primarily mono- and diglucosides of zeaxanthin. We have cloned and expressed the gene for the enzyme that catalyzes the glucosylation of zeaxanthin. The enzyme has an apparent molecular mass of 45 kDa on an SDS/polyacrylamide gel, which is consistent with its calculated molecular mass. In vitro enzymatic activity was demonstrated using UDP-[14C]glucose and zeaxanthin as substrates. The product zeaxanthin diglucoside and its intermediate monoglucoside were identified by thin layer chromatography. The optimum pH and temperature ranges of the enzyme are 7.0-7.5 and 32-37 degrees C, respectively. A hydropathy plot indicates no apparent membrane-spanning regions, and biochemical experiments suggest that the enzyme is weakly membrane-associated. The amino acid sequence derived from the zeaxanthin glucosyltransferase gene shows a small region of high similarity with other glucuronosyl- and glucosyltransferases that use either UDP-activated glucuronic acid or a sugar as one of their substrates. Based on these similarities, we propose that this conserved sequence is part of the UDP binding site.
Sorption Behavior of Radionuclides on Crystalline Synthetic Tunnel Manganese Oxides (2000)

Cryptomelane-type (potassium) and todorokite-type (magnesium and calcium) manganese oxides were prepared and studied for the removal of radionuclides from aqueous solutions containing inactive metal ions of interest in radionuclide-bearing nuclear waste effluents. Batch distribution coefficients were measured as a function of pH and sodium, potassium, magnesium, and calcium ion concentrations. Trace strontium (89Sr) and cesium (137Cs) ions were taken up by ion-exchange mechanisms. Selectivity coefficients were estimated as KCs/K = 0.6 and KSr/K = 1.0 for cryptomelane and KCs/Mg = 7550, KSr/Mg = 50, and KSr/Ca = 10 for todorokite. The cryptomelane analogue was particularly effective for the separation of trace silver ions (110Ag) in low-pH solutions. Todorokite analogues were effective for a wider range of radionuclides, including 57Co across a wide pH range (1−10) and 137Cs in acidic solution. The affinity sequence for magnesium and calcium ion-extracted (acid-treated) todorokites in 0.1 HNO3 was 137Cs > 59Fe > 51Cr ≈ 57Co ≈ 241Am > 54Mn > 63Ni > 65Zn > 236Pu > 89Sr.
The CHARGE Study: An Epidemiologic Investigation of Genetic and EnvironmentalFactors Contributing to Autism (2006)

Causes and contributing factors for autism are poorly understood. Evidence suggests that prevalence is rising, but the extent to which diagnostic changes and improvements in ascertainment contribute to this increase is unclear. Both genetic and environmental factors are likely to contribute etiologically. Evidence from twin, family, and genetic studies supports a role for an inherited predisposition to the development of autism. Nonetheless, clinical, neuroanatomic, neurophysiologic, and epidemiologic studies suggest that gene penetrance and expression may be influenced, in some cases strongly, by the prenatal and early postnatal environmental milieu. Sporadic studies link autism to xenobiotic chemicals and/or viruses, but few methodologically rigorous investigations have been undertaken. In light of major gaps in understanding of autism, a large case-control investigation of underlying environmental and genetic causes for autism and triggers of regression has been launched. The CHARGE (Childhood Autism Risks from Genetics and Environment) study will address a wide spectrum of chemical and biologic exposures, susceptibility factors, and their interactions. Phenotypic variation among children with autism will be explored, as will similarities and differences with developmental delay. The CHARGE study infrastructure includes detailed developmental assessments, medical information, questionnaire data, and biologic specimens. The CHARGE study is linked to University of California-Davis Center for Children's Environmental Health laboratories in immunology, xenobiotic measurement, cell signaling, genomics, and proteomics. The goals, study design, and data collection protocols are described, as well as preliminary demographic data on study participants and on diagnoses of those recruited through the California Department of Developmental Services Regional Center System.
Sonography of the Primary Cutaneous Melanoma: A Review (2012)

The diagnosis and management of primary cutaneous melanoma have traditionally relied on clinical and histological characteristics. Nevertheless, in recent years there has been a significant growth in the usage of ultrasound for studying the cutaneous layers. Thus, the present paper focuses on the primary lesion, its sonographic characteristics, the potential benefits of early imaging, and the new developments on the ultrasound field applied to cutaneous melanoma.
Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor (2004)

Histone deacetylases (HDACs) are a family of enzymes involved in the regulation of gene expression, DNA repair, and stress response. These processes often are altered in tumors, and HDAC inhibitors have had pronounced antitumor activity with promising results in clinical trials. Here, we report the crystal structure of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a eukaryotic zinc-dependent HDAC has not be described previously. Similar to bacterial HDAC-like protein, HDAC8 folds in a single alpha/beta domain. The inhibitor and the zinc-binding sites are similar in both proteins. However, significant differences are observed in the length and structure of the loops surrounding the active site, including the presence of two potassium ions in HDAC8 structure, one of which interacts with key catalytic residues. CD data suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical cancer cell lines, highlighting the importance of this HDAC subtype for tumor cell proliferation. Our findings open the way for the design and development of selective inhibitors of HDAC8 as possible antitumor agents.
The importance of the location of antibody binding on the M6 protein for opsonization and phagocytosis of group A M6 streptococci. (1988)

One of 19 mAbs against the native group A streptococcal M6 protein proved opsonic for type 6 organisms in a bactericidal assay. The opsonic and three nonopsonic antibodies were selected for isotype and complement fixation studies based on previous knowledge of their epitope site on the M6 molecule. While mAb 3B8 (IgG3), whose epitope is in the NH2-terminal hypervariable region of the molecule (distal from the cell), and mAbs 10B6 (IgG2a) and 10F5 (IgG2b), both located in the conserved central region of the molecule, all fix complement, 10A11 (IgG1) did not. Only mAb 3B8 was opsonic despite the fact that mAbs 10B6 and 10F5 both exhibited similar complement-fixing capacity, binding titer, and surface exposure of epitopes. Analysis of antibodies raised against synthetic peptides representing various regions of the M6 protein showed that only the amino-terminal peptide (residues 1-21) was capable of eliciting opsonic antibodies, despite the fact that peptides from other areas produced antibodies with high-binding titers to the native M6 protein and also with the ability to bind to intact streptococcal cells. These results not only support the observed type specificity of opsonic antibodies, but also clearly point to the importance of the location of antibody binding on the M molecule relative to the actual functional capacity of the antibody with respect to the opsonization and phagocytosis of M6 streptococci. These results may underscore the recently observed role of complement Factor H in the antiphagocytic activity of the M protein.
美国印第安学校中学女生的未来——基于“可能自我”的个案研究 (2010)

本质化研究以美国中字的四位印弟安女生为个案，重点阐释了她们的中字课堂受教经历对其今后成长的影响。本文采用“可能自我理论”，对访谈资料进行了审视和分析，所涉主题包括学校问题、教师、关系的重要性及未来计划这样四大方面。结果表明，“可能自我理论”有助于人们理解这些中学女生是怎样看待她们自己和筹划她们未来的，同时也为解决和预防中学生的辍学问题，提供了一种可能的路径。
A new method for the selection of protein interactions in mammalian cells (2000)

In the present study we present a new method that allows for the selection of protein interactions in mammalian cells. We have used this system to verify two interactions previously characterized in vitro. (1) The interaction between human TATA-binding protein 1 and nuclear factor ĸB and (2) the association of Homo sapiens nuclear autoantigen SP100B with human heterochromatin protein 1α, a protein implicated in chromatin remodelling. We observe for the first time that these interactions also occur in vivo. One protein was fused to the N-terminal half of ubiquitin, while the interacting partner was fused to the C-terminal half of ubiquitin, that was itself linked to guanine phosphoryltransferase 2 (gpt2) modified to begin with an arginine residue. Upon interaction of both proteins, ubiquitin is reconstituted, and its association with the Rgpt2 reporter is subsequently cleaved off by ubiquitin-processing enzymes. The presence of arginine in the Rgpt2 gene product leads to the degradation of the product by the N-end rule pathway. In the human fibroblast cell line HT1080HPRT- (that is deficient in the enzyme for hypoxanthine-guanine phosphoribosyltransferase) cells in which interaction between both proteins of interest occurs can then be selected for by hypoxanthine/aminopterin/thymine medium and counterselected against by 6-thioguanine medium. This method provides a suitable alternative to the yeast two-hybrid system and is generally applicable.
Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents (2005)

To further explore the nature of the mitochondrial dysfunction and insulin resistance that occur in the muscle of young, lean, normoglycemic, insulin-resistant offspring of parents with type 2 diabetes (IR offspring), we measured mitochondrial content by electron microscopy and insulin signaling in muscle biopsy samples obtained from these individuals before and during a hyperinsulinemic-euglycemic clamp. The rate of insulin-stimulated muscle glucose uptake was approximately 60% lower in the IR offspring than the control subjects and was associated with an approximately 60% increase in the intramyocellular lipid content as assessed by H magnetic resonance spectroscopy. Muscle mitochondrial density was 38% lower in the IR offspring. These changes were associated with a 50% increase in IRS-1 Ser312 and IRS-1 Ser636 phosphorylation and an approximately 60% reduction in insulin-stimulated Akt activation in the IR offspring. These data provide new insights into the earliest defects that may be responsible for the development of type 2 diabetes and support the hypothesis that reductions in mitochondrial content result in decreased mitochondrial function, which predisposes IR offspring to intramyocellular lipid accumulation, which in turn activates a serine kinase cascade that leads to defects in insulin signaling and action in muscle.
In Vivo Priming by DNA Injection Occurs Predominantly by Antigen Transfer (1999)

DNA vaccines can stimulate both humoral and cytolytic immune responses. Although bone marrow-derived elements present the expressed Ag, the mechanisms for acquiring immunogenic peptides have yet to be fully elucidated. APCs may become directly transfected by plasmid DNA or process extracellular proteins produced by other transfected cells. Using a transactivating plasmid system and bone marrow chimeras, we show that both mechanisms appear to be involved; however, the bulk of the immune response is dependent on expression of Ag by nonlymphoid tissues and transfer to APCs. These in vivo studies are the first to define the role of transfected nonlymphoid cells in generating Ag for presentation by bone marrow-derived APCs after needle injection with plasmid DNA.
Extractable Surface Hydrocarbons of Workers and Drones of the GenusApis (1985)

SummaryExtractable surface hydrocarbons of adults of various ages chosen at random from species of honeybees (Apis florea, A. dorsata, A. mellifera and A. cerana), and newly-emerged adult workers of subspecies of A. mellifera were analysed by gas chromatography and by combined gas chromatography and mass spectrometry. There were significant quantitative and qualitative differences between the hydrocarbons of the 4 species of Apis. The quantity of hydrocarbon per bee was higher for A. dorsata and A. cerana than for A. mellifera, and even the quantity found in the much smaller A. florea approached that of A. mellifera. The major hydrocarbons of the surface waxes of A. florea, A. mellifera, and A. cerana were normal alkanes and alkenes. For A. dorsata, there was also a substantial proportion of branched alkanes. Small quantities of branched alkanes were found in the surface waxes of A. mellifera and A. cerana, but only traces were found in those of A. florea. Compared with workers, drones of A. dorsata and A. cerana had higher proportions of branched alkanes and short-chain alkenes and lower proportions of normal alkanes and long-chain alkenes. For random-age bees, the unsaturated hydrocarbons of A. mellifera adansonii covered a wider range of chain lengths than those of the other A. mellifera subspecies. The quantities of hydrocarbons extracted per individual from samples of newly-emerged worker bees of different subspecies of A. mellifera were consistent and the gas chromatograms showed only minor variations. Honeybees from South Africa (A. m. adansonii and A. m. capensis) and ‘Africanized’ bees from Brazil had a substantially higher proportion of C35 unsaturated hydrocarbons than bees of European origin (A. m. mellifera, A. m. ligustica, and A. m. camica).