gebhart/patrepeval huggingface dataset:
Long-Term Cultured Human Skin Mast Cells Are Suitable for Pharmacological Studies of Anti-Allergic Drugs Due to High Responsiveness to FcεRI Cross-Linking (2011)

Human skin mast cells proliferated in the presence of interleukin (IL)-4+SCF (expanding 18-fold in 8 weeks) and acquired profound responsiveness towards high affinity IgE receptor (FcεRI) cross-linking, liberating about 75% of their histamine. In a proof-of-concept, we found that these cells are useful for pharmacological testing. Even a subtle inhibition of degranulation can be visualized. This model might prove valuable in tests of novel anti-allergic drugs.
RAD51 Up-regulation Bypasses BRCA1 Function and Is a Common Feature of BRCA1 -Deficient Breast Tumors (2007)

The breast cancer susceptibility gene BRCA1 encodes a large protein thought to contribute to a variety of cellular processes, although the critical determinants of BRCA1-deficient tumorigenesis remain unclear. Given that BRCA1 is required for cell proliferation, suppressor mutations are believed to modify BRCA1 phenotypes and contribute to the etiology of BRCA1-deficient tumors. Here, we show that overexpression of the homologous recombinase RAD51 in a DT40 BRCA1Delta/Delta mutant rescues defects in proliferation, DNA damage survival, and homologous recombination (HR). In addition, epistasis analysis with BRCA1 and the DNA end-joining factor KU70 indicates that these factors operate independently of one another to repair double-strand breaks. Consistent with this genetic finding, cell synchronization studies show that the ability of BRCA1 to promote radioresistance is restricted to the late S and G2 phases of the cell cycle, as predicted for genes whose function is specific to homology-mediated repair rather than nonhomologous end-joining. Notably, retrospective analyses of microarray expression data reveal elevated expression of RAD51 and two of its late-acting cofactors, RAD54 and RAD51AP1, in BRCA1-deficient versus sporadic breast tumors. Taken together, our results indicate that up-regulation of HR provides a permissive genetic context for cells lacking BRCA1 function by circumventing its requirement in RAD51 subnuclear assembly. Furthermore, the data support a model in which enhanced HR activity contributes to the etiology of BRCA1-deficient tumors.
Size does matter: overcoming the adeno-associated virus packaging limit (2000)

Recombinant adeno-associated virus (rAAV) vectors mediate long-term gene transfer without any known toxicity. The primary limitation of rAAV has been the small size of the virion (20 nm), which only permits the packaging of 4.7 kilobases (kb) of exogenous DNA, including the promoter, the polyadenylation signal and any other enhancer elements that might be desired. Two recent reports (D Duan et al: Nat Med 2000, 6:595-598; Z Yan et al: Proc Natl Acad Sci USA 2000, 97:6716-6721) have exploited a unique feature of rAAV genomes, their ability to link together in doublets or strings, to bypass this size limitation. This technology could improve the chances for successful gene therapy of diseases like cystic fibrosis or Duchenne muscular dystrophy that lead to significant pulmonary morbidity.
Detection of glutamic acid decarboxylase autoantibodies with the varelisa ELISA (1995)

Journal Article Detection of glutamic acid decarboxylase autoantibodies with the varelisa ELISA Get access A M Gronowski, A M Gronowski Dept. of Pathol., Washington Univ. School of Med., St. Louis Children's Hosp., MO 63110, USA Search for other works by this author on: Oxford Academic Google Scholar E C Wong, E C Wong Dept. of Pathol., Washington Univ. School of Med., St. Louis Children's Hosp., MO 63110, USA Search for other works by this author on: Oxford Academic Google Scholar T R Wilhite, T R Wilhite Dept. of Pathol., Washington Univ. School of Med., St. Louis Children's Hosp., MO 63110, USA Search for other works by this author on: Oxford Academic Google Scholar D L Martin, D L Martin Dept. of Pathol., Washington Univ. School of Med., St. Louis Children's Hosp., MO 63110, USA Search for other works by this author on: Oxford Academic Google Scholar C H Smith, C H Smith Dept. of Pathol., Washington Univ. School of Med., St. Louis Children's Hosp., MO 63110, USA Search for other works by this author on: Oxford Academic Google Scholar C A Parvin, C A Parvin Dept. of Pathol., Washington Univ. School of Med., St. Louis Children's Hosp., MO 63110, USA Search for other works by this author on: Oxford Academic Google Scholar M Landt M Landt Dept. of Pathol., Washington Univ. School of Med., St. Louis Children's Hosp., MO 63110, USA Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 41, Issue 10, 1 October 1995, Pages 1532–1534, https://doi.org/10.1093/clinchem/41.10.1532 Published: 01 October 1995
TO THE SAME (2011)

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Transformation of the cyanobacterium Anacystis nidulans 6301 with the Escherichia coli plasmid pBR322. (1986)

Anacystis nidulans 6301 has been transformed in the light to ampicillin resistance with the plasmid pBR322. Permeaplasts prepared by 2-hr treatment of cells with lysozyme and EDTA are transformed with a 50-fold higher efficiency than that observed for cells. beta-Lactamase is present in A. nidulans transformed either with pBR322 or the plasmid pCH1 as evidenced by hydrolysis of the beta-lactam ring of Nitrocefin in extracts of transformants. beta-Lactamase also can be immunoprecipitated from extracts of [35S]methionine-labeled pBR322 transformants and coprecipitates with ribulose-bisphosphate carboxylase. Expression of the carboxylase is apparently amplified in pBR322 transformants as is that for several soluble proteins in pCH1 transformants. Chromosomal DNA per cell is increased about 6-fold after transformation of A. nidulans 6301 with either pBR322 or pCH1. A 4.3-kilobase-pair plasmid can be isolated from pBR322 transformants in addition to the endogenous plasmids pUH24 and pUH25.
Bacteria and cancer: cause, coincidence or cure? A review (2006)

Research has found that certain bacteria are associated with human cancers. Their role, however, is still unclear. Convincing evidence links some species to carcinogenesis while others appear promising in the diagnosis, prevention or treatment of cancers. The complex relationship between bacteria and humans is demonstrated by Helicobacter pylori and Salmonella typhi infections. Research has shown that H. pylori can cause gastric cancer or MALT lymphoma in some individuals. In contrast, exposure to H. pylori appears to reduce the risk of esophageal cancer in others. Salmonella typhi infection has been associated with the development of gallbladder cancer; however S. typhi is a promising carrier of therapeutic agents for melanoma, colon and bladder cancers. Thus bacterial species and their roles in particular cancers appear to differ among different individuals. Many species, however, share an important characteristic: highly site-specific colonization. This critical factor may lead to the development of non-invasive diagnostic tests, innovative treatments and cancer vaccines.
T Cell Infiltration into Class II MHC-Disparate Allografts and Acute Rejection Is Dependent on the IFN-γ-Induced Chemokine Mig (1999)

Direct evidence that cytokines with chemoattractant properties for leukocytes, chemokines, recruit alloantigen-primed T cells into transplanted allografts has been lacking. We present evidence that neutralization of a single chemokine inhibits T cell infiltration into class II MHC-disparate murine allografts and acute rejection. The chemokines IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma (Mig) are expressed in allogeneic skin grafts during the late stages of acute rejection. Survival of class II MHC-disparate B6.H-2bm12 allografts is prolonged from day 14 to day 55 posttransplant when C57BL/6 recipients are given a short course treatment with an antiserum to Mig. This treatment also inhibits T cell and macrophage infiltration into the allografts. B6.H-2bm12 allografts are also not rejected by IFN-gamma-/- C57BL/6 recipients. Injection of Mig directly into B6.H-2bm12 grafts on IFN-gamma-deficient recipients restores T cell infiltration and rejection. Therefore, the inability of IFN-gamma-deficient recipients to reject the class II MHC-disparate allografts is due to the lack of intraallograft Mig production and alloantigen-primed T cell recruitment to the graft. These results indicate for the first time the potential utility of chemokine neutralization strategies in preventing T cell infiltration into allografts and abrogating acute rejection.
Involvement of annexin V in the entry of influenza viruses and role of phospholipids in infection (1996)

Influenza viruses bind to annexin V, a widely spread non-glycosylated phospholipid-binding protein. Externally added phospholipids as well as antiserum against this protein specifically inhibit infection of these viruses in cell cultures. We conclude that annexin V plays an important role in the entry of these viruses.
Raman-scattering study of exciton-phonon coupling in PbS nanocrystals (1997)

The exciton-phonon coupling strength of PbS nanocrystals that strongly confine both charge carriers is investigated using resonant Raman scattering. The strength of this coupling (Huang-Rhys parameter S\ensuremath{\sim}0.7) is four orders of magnitude greater than that predicted theoretically for the intrinsic states of the nanocrystal, but is the same order of magnitude as that measured for Cd(S,Se) nanocrystals. The large exciton-phonon coupling is consistent with one charge carrier being localized at the surface of the nanocrystal.
Neuregulin-4 Is a Survival Factor for Colon Epithelial Cells both in Culture and in Vivo (2012)

Expression of the ErbB4 tyrosine kinase is elevated in colonic epithelial cells during inflammatory bowel disease, whereas ErbB4 overexpression in cultured colonocytes blocks TNF-induced apoptosis in a ligand-dependent manner. Together, these observations suggest that ErbB4 induction may be a protective response. However, the effects of ErbB4 signaling in the colonic epithelium in vivo are not known. Furthermore, previous work on ErbB4 used ligands shared with other receptors, raising the question of whether the observed responses are explicitly due to ErbB4. In this study, we used the ErbB4-specific ligand neuregulin-4 (NRG4) to activate ErbB4 and define its role in colonocyte biology. NRG4 treatment, either in cultured cells or in mice, blocked colonic epithelial apoptosis induced by TNF and IFN-γ. It was also protective in a murine experimental colitis model. NRG4 stimulated phosphorylation of ErbB4 but not other ErbB receptors, indicating that this is a specific response. Furthermore, in contrast to related ligands, NRG4 enhanced cell survival but not proliferation or migration, and stimulated phosphorylation of the anti-apoptotic mediator Akt but not ERK MAPK. Pharmacological inhibition of PI3K/Akt signaling reversed the anti-apoptotic effects of NRG4, confirming the role of this cascade in NRG4-induced cell survival. With regard to the potential clinical importance of this pathway, NRG4 expression was decreased in human inflammatory bowel disease samples and mouse models of colitis, suggesting that activation of ErbB4 is altered in disease. Thus, exogenous NRG4 may be beneficial for disorders in which epithelial apoptosis is part of the pathology.
Synthetic DNA and Biology (Nobel Lecture) (1994)

Abstract Most of the significant work has been summarized in a number of reviews and articles. In these there was, of necessity, a good deal of simplification and omission of detail…. With the passage of time, even I find myself accepting such simplified accounts. F Sanger [1]
Evaluation of thyroid function in neonatal and adult rats: The neglected endocrine mode of action (2003)

Although known to regulate growth and development, cellular metabolism, the use of oxygen, and basal metabolic rate, thyroid hormones have been only minimally evaluated in neonatal rodents at critical times of development. Despite some modulation of metabolic rate by other hormones, such as testosterone, growth hormone, and norepinephrine, 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) are the most important metabolic rate modulators. Endpoints used for thyroid function assessment in neonatal and adult rats include thyroid-stimulating hormone (TSH), T3, and T4 levels and histopathology. In rodents, decreased serum levels of T3 and T4 and increased serum TSH levels, with sustained release of TSH and resultant follicular cell hypertrophy/hyperplasia, are typical hormonal and histopathological findings attributable to compounds altering thyroid function. Hypothyroidism early in the neonatal period can affect reproductive endpoints in both male and female rats, with the critical period of exposure being the first two weeks postnatal. Hypothyroidism has been shown to reduce gonadotrophin levels and delay pubertal spermatogenesis in male rats and to block gonadotropin-induced first ovulation in immature female rats by decreasing FSH and luteinizing hormone (LH) serum concentrations. Inclusion of evaluations of TSH, T3, and T4 assays in multigeneration and developmental neurotoxicity protocols may assist in risk assessments.
Application of recombinant DNA techniques to structure-function studies of equine protein hormones. (1987)

Complementary (c)DNA libraries have been made from horse pituitary gland and endometrial cup tissues with the aim of isolating the genes for the horse gonadotrophins (FSH, LH and CG) and growth hormone (GH). Southern (DNA) and Northern (RNA) blotting techniques were used to demonstrate that several heterologous (human and ovine) cDNA probes would be adequate for isolating the horse genes. A human cDNA probe was then used to isolate the horse gonadotrophin alpha-subunit cDNA from the pituitary and endometrial cup libraries. The nucleotide sequences from both tissue sources were identical, thereby confirming that there is a single gene for the alpha-subunit in the horse. As soon as the gonadotrophin beta-subunit sequences become available, they will be expressed along with the alpha-subunit to obtain biologically active hormones. Horse GH cDNA has also been isolated by using a sheep cDNA probe and its DNA sequence has been determined. It was subsequently used to demonstrate that horse endometrial cups, but not the allantochorion taken at the same stage of gestation, contains mRNA for a GH-like protein. This mRNA could be due to a low level of expression of the GH gene or to expression of the gene(s) for a GH-related protein such as prolactin or placental lactogen.
A selective transcriptional induction system for mammalian cells based on Gal4-estrogen receptor fusion proteins. (1993)

Most mammalian cells neither express any Gal4-like activity nor endogenous estrogen receptor, thus rendering estrogen an inert signal for them. For these two reasons we have developed a selective induction system based on the estrogen-regulable transcription factor Gal-ER. Gal-ER consists of the DNA-binding domain of the yeast Gal4 protein fused to the hormone-binding domain of the human estrogen receptor and hence should exclusively regulate a transfected gene under the control of a Gal4-responsive promoter in mammalian cells. Two major improvements of this induction system were made. First, a synthetic Gal4-responsive promoter was constructed which consisted of four Gal4-binding sites, an inverted CCAAT element, a TATA box, and the adenovirus major late initiation region. This promoter showed extremely low basal activity in the absence and high inducibility in the presence of ligand-activated Gal-ER. Second, the transcription factor Gal-ER was rendered more potent and less susceptible to cell type-specific variation by fusing the strong activating domain of the herpesvirus protein VP16 onto its C terminus. In response to estrogen, Gal-ER-VP16 induced the Gal4-responsive promoter at least 100-fold in transiently transfected NIH 3T3 and P19 cells. Rat fibroblast cell lines expressing integrated Gal-ER and Gal4-responsive fos genes were transformed in a strictly estrogen-dependent manner. The exogenous fos gene was rapidly induced to maximal levels within 1-2 hr of estrogen addition. Elevated Fos activity in turn stimulated transcription of the endogenous fra-1 gene. These data demonstrate the utility of the Gal-ER induction system as a powerful genetic switch for regulating heterologous genes and, in particular, for identifying Fos targets in mammalian cells.
Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture. (1991)

We have recently described a nonnucleoside compound that specifically inhibits the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS. This compound, nevirapine (BI-RG-587), interacts with highly conserved tyrosine residues at positions 181 and 188 in the reverse transcriptase to inhibit the recombinant enzyme and virus replication in cell culture with 50% inhibitory concentrations in the 40 nM range. HIV-1 variants resistant to nevirapine emerged with passage in cell culture in the presence of drug. This resistant phenotype was stable with continued passage in the absence of drug. These mutants had a substitution of cysteine for the tyrosine at position 181. Introduction of this mutation into the recombinant enzyme increased the inhibitory concentration of nevirapine 100-fold. Substitution of cysteine for tyrosine at residue 181 into the wild-type viral genome conferred a similar reduction in susceptibility to nevirapine. Mutants were also resistant to a tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione derivative and two 6-phenylthiouracil derivatives but retained their sensitivity to the other reverse transcriptase inhibitors, 3'-azido-3'-deoxythymidine and foscarnet.
Double-strand-break-induced homologous recombination in mammalian cells (2001)

In mammalian cells, the repair of DNA double-strand breaks (DSBs) occurs by both homologous and non-homologous mechanisms. Indirect evidence, including that from gene targeting and random integration experiments, had suggested that non-homologous mechanisms were significantly more frequent than homologous ones. However, more recent experiments indicate that homologous recombination is also a prominent DSB repair pathway. These experiments show that mammalian cells use homologous sequences located at multiple positions throughout the genome to repair a DSB. However, template preference appears to be biased, with the sister chromatid being preferred by 2–3 orders of magnitude over a homologous or heterologous chromosome. The outcome of homologous recombination in mammalian cells is predominantly gene conversion that is not associated with crossing-over. The preference for the sister chromatid and the bias against crossing-over seen in mitotic mammalian cells may have developed in order to reduce the potential for genome alterations that could occur when other homologous repair templates are utilized. In attempts to understand further the mechanism of homologous recombination, the proteins that promote this process are beginning to be identified. To date, four mammalian proteins have been demonstrated conclusively to be involved in DSB repair by homologous recombination: Rad54, XRCC2, XRCC3 and BRCAI. This paper summarizes results from a number of recent studies.
Allopregnanolone Levels and Symptom Improvement in Severe Premenstrual Syndrome (2002)

Allopregnanolone is a neuroactive metabolite of progesterone and a barbiturate-like modulator of central gamma-aminobutyric acid receptors that modify a range of behaviors, including the stress response. The aim of this study was to determine the association of allopregnanolone levels with improvement of mood and behavioral symptoms following antidepressant treatment for severe premenstrual syndrome. A second exploratory aim was to determine whether allopregnanolone levels differed between antidepressant and placebo treatments. Serum samples from 46 women who were treated with sertraline, desipramine, or placebo in double-blind conditions were assayed. Improvement was assessed as the percent change from the pretreatment baseline in premenstrual symptoms, which were rated daily by the subjects. Twenty-seven samples were from improved subjects and 19 samples were from unimproved subjects following 2 to 3 months of double-blind treatment. Posttreatment allopregnanolone levels were significantly lower in the improved compared with the unimproved subjects. Improvement was also significantly associated with lower allopregnanolone levels for premenstrual depression and appetite changes. Improvement remained significantly associated with lower allopregnanolone levels after adjustment for treatment, cycle day of blood draw, age, and the interaction of treatment and cycle day. These preliminary results offer the first placebo-controlled evidence of association between allopregnanolone levels and premenstrual syndrome treatment response and suggest the importance of further study of the associations of allopregnanolone with premenstrual syndromes and the role of allopregnanolone in response to antidepressant medications.
Sustained growth in primary culture of normal mammary epithelial cells embedded in collagen gels (1980)

Normal mammary epithelial cells from BALB/cfC3H midpregnant mice were freed from stromal cell types by Percoll density gradient centrifugation after collagenase digestion and were then embedded within collagen gels. Sustained growth leading to an increase in cell number was accomplished in response to cholera toxin and high concentrations of horse serum. The extent of growth was found to be dependent on the horse serum concentration, the maximum growth being attained at 50%. A serum concentration of 12.5% horse serum and 2.5% fetal calf serum, along with cholera toxin at 0.01 mug/ml, allowed maintenance but failed to cause any significant increase in cell number during the experimental period of 2 weeks. This same maintenance medium was used to determine the effects of various exogenously added steroids, protein hormones, and organ extracts on the proliferation of mammary epithelial cells in culture. Hormones failed to elicit any proliferative response, but extracts of kidney, brain, uterus, and spleen produced proliferative responses equal to or greater than the response obtained with 50% horse serum and cholera toxin. Kidney extracts prepared from midpregnant mice, virgin mice, and virgin mice given pituitary isografts all showed comparable activities, suggesting that the concentration of stimulatory factor(s) was not influenced by the hormonal status of the donor. Normal mammary epithelial cells that had undergone a 10- to 15-fold increase in cell number over initial values during 2-3 weeks in culture were passaged to secondary gel cultures. Outgrowth similar to those seen in primary culture were seen again in secondary culture. The present system provides a method for sustaining growth in culture of primary mammary epithelial cells from normal tissues.
Internet Banking: Client-Side Attacks and Protection Mechanisms (2009)

Although current mechanisms protect against offline credential-stealing attacks, effective protection against online channel-breaking attacks requires technologies to defeat man-in-the-middle (MITM) attacks, and practical protection against content-manipulation attacks requires transaction-authentication technologies.