gebhart/patrepeval huggingface dataset:
Incomplete block of B cell development and immunoglobulin production in mice carrying the ? MT mutation on the BALB/c background (2002)

The expression of the preB cell receptor (preBCR), composed of the mu chain, surrogate light chains and the Igalpha /Igbeta signal transduction unit, permits further differentiation of Bcell precursors. C57BL/6 mice homozygous for an inactivating mutation of the membrane exon of the mu chain gene (C57BL/6muMT/muMT)) cannot form a preBCR and are, consequently, devoid of mature B lymphocytes. Here we present evidence that the block of B cell development by the muMT mutation is incomplete in BALB/c mice. Unlike C57BL/6muMT/muMT), BALB/cmuMT/muMT) mice generate small numbers of mature B cells, accumulate plasma cells and produce high levels of all immunoglobulin isotypes, except IgM. The observed phenomenon seems to be controlled by a single genetic locus that is not linked to IgH.
Disruption of Wild-Type IDH1 Suppresses D-2-Hydroxyglutarate Production in IDH1-Mutated Gliomas (2012)

Point mutations at Arg132 of the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the "oncometabolite" D-2-hydroxyglutarate (D-2HG). The mutated IDH1 allele is usually associated with a wild-type IDH1 allele (heterozygous) in cancer. Here, we identify 2 gliomas that underwent loss of the wild-type IDH1 allele but retained the mutant IDH1 allele following tumor progression from World Health Organization (WHO) grade III anaplastic astrocytomas to WHO grade IV glioblastomas. Intratumoral D-2HG was 14-fold lower in the glioblastomas lacking wild-type IDH1 than in glioblastomas with heterozygous IDH1 mutations. To characterize the contribution of wild-type IDH1 to cancer cell D-2HG production, we established an IDH1-mutated astrocytoma (IMA) cell line from a WHO grade III anaplastic astrocytoma. Disruption of the wild-type IDH1 allele in IMA cells by gene targeting resulted in an 87-fold decrease in cellular D-2HG levels, showing that both wild-type and mutant IDH1 alleles are required for D-2HG production in glioma cells. Expression of wild-type IDH1 was also critical for mutant IDH1-associated D-2HG production in the colorectal cancer cell line HCT116. These insights may aid in the development of therapeutic strategies to target IDH1-mutated cancers.
ERK1/ERK2 MAPK Signaling is Required to Increase Myelin Thickness Independent of Oligodendrocyte Differentiation and Initiation of Myelination (2012)

Wrapping of the myelin sheath around axons by oligodendrocytes is critical for the rapid conduction of electrical signals required for the normal functioning of the CNS. Myelination is a multistep process where oligodendrocytes progress through a well coordinated differentiation program regulated by multiple extracellular growth and differentiation signals. The intracellular transduction of the extracellular signals that regulate myelination is poorly understood. Here we demonstrate a critical role for two important signaling molecules, extracelluar signal-regulated protein kinases 1 and 2 (ERK1/ERK2), downstream mediators of mitogen-activated protein kinases, in the control of CNS myelin thickness. We generated and analyzed two lines of mice lacking both ERK1/ERK2 function specifically in oligodendrocyte-lineage cells. In the absence of ERK1/ERK2 signaling NG2⁺ oligodendrocyte progenitor cells proliferated and differentiated on schedule. Mutant oligodendrocytes also ensheathed axons normally and made a few wraps of compact myelin. However, the subsequent increase in myelination that correlated myelin thickness in proportion to the axon caliber failed to occur. Furthermore, although the numbers of differentiated oligodendrocytes in the adult mutants were unchanged, they showed an inability to upregulate the transcription of major myelin genes that normally occurs during active myelination. Similarly, in vitro ERK1/ERK2-deficient oligodendrocytes differentiated normally but failed to form typical myelin-like membrane sheets. None of these effects were observed in single ERK1 or ERK2 mutants. These studies suggest that the predominant role of ERK1/ERK2 signaling in vivo is in promoting rapid myelin growth to increase its thickness, subsequent to oligodendrocyte differentiation and the initiation of myelination.
Induction of cyclooxygenase-2 by interleukin-1 alpha. Evidence for post-transcriptional regulation. (1994)

Prostanoids, produced by diverse cell types, modulate a variety of pathophysiological processes. The rate of prostanoid synthesis is determined, in part, by the levels of prostanoid-synthetic enzymes, such as cyclooxygenase (Cox), a rate-limiting enzyme in the conversion of arachidonic acid to prostanoids. While two Cox genes have been identified, Cox-2 is unique because it is highly induced in response to cell activation processes including inflammation. We have studied the effect of interleukin-1 alpha (IL-1 alpha), a proinflammatory cytokine that facilitates its actions in part by inducing the synthesis of prostanoids, on the expression of Cox-2 in a human cell line (ECV304) and demonstrated that IL-1 alpha induces a sustained increase in the expression of the Cox-2 mRNA as well as the functional enzyme. Three mechanistically distinct inhibitors of translation stimulated the expression of the Cox-2 mRNA and potentiated the effect of IL-1 alpha. Furthermore, IL-1 alpha induced rapid but transient activation of Cox-2 transcription and, in the absence of transcription, prolonged the half-life of the Cox-2 mRNA. Together, these data suggest that post-transcriptional mechanisms are important in the sustained induction of the Cox-2 mRNA and that IL-1 alpha may increase the stability of the Cox-2 transcript.
Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. (1994)

To define the role of the human immunodeficiency virus type 1 (HIV-1) envelope proteins in virus infection, a series of peptides were synthesized based on various regions of the HIV-1 transmembrane protein gp41. One of these peptides, DP-178, corresponding to a region predictive of alpha-helical secondary structure (residues 643-678 of the HIV-1LAI isolate), has been identified as a potent antiviral agent. This peptide consistently blocked 100% of virus-mediated cell-cell fusion at < 5 ng/ml (IC90 approximately 1.5 ng/ml) and gave an approximately 10 times reduction in infectious titer of cell-free virus at approximately 80 ng/ml. The inhibitory activity was observed at peptide concentrations approximately 10(4) to 10(5) times lower than those at which cytotoxicity and cytostasis were detected. Peptide-mediated inhibition is HIV-1 specific in that approximately 10(2) to 10(3) times more peptide was required for inhibition of a human immunodeficiency virus type 2 isolate. Further experiments showed that DP-178 exhibited antiviral activity against both prototypic and primary HIV-1 isolates. As shown by PCR analysis of newly synthesized proviral DNA, DP-178 blocks an early step in the virus life cycle prior to reverse transcription. Finally, we discuss possible mechanisms by which DP-178 may exert its inhibitory activity.
Discordant antigenic drift of neuraminidase and hemagglutinin in H1N1 and H3N2 influenza viruses (2011)

Seasonal epidemics caused by influenza virus are driven by antigenic changes (drift) in viral surface glycoproteins that allow evasion from preexisting humoral immunity. Antigenic drift is a feature of not only the hemagglutinin (HA), but also of neuraminidase (NA). We have evaluated the antigenic evolution of each protein in H1N1 and H3N2 viruses used in vaccine formulations during the last 15 y by analysis of HA and NA inhibition titers and antigenic cartography. As previously shown for HA, genetic changes in NA did not always lead to an antigenic change. The noncontinuous pattern of NA drift did not correspond closely with HA drift in either subtype. Although NA drift was demonstrated using ferret sera, we show that these changes also impact recognition by NA-inhibiting antibodies in human sera. Remarkably, a single point mutation in the NA of A/Brisbane/59/2007 was primarily responsible for the lack of inhibition by polyclonal antibodies specific for earlier strains. These data underscore the importance of NA inhibition testing to define antigenic drift when there are sequence changes in NA.
The Preparation of Nucleotide-Protein Conjugates: Carbodiimides as Coupling Agents (1966)

Abstract For some time it has been apparent that antibodies might be useful in the study of the fine structure of RNA and DNA. A major stumbling block has been the unavailability of a method which would render polynucleotides antigenic yet largely preserve their structural integrity. In approaching the problem of covalently conjugating polynucleotides to proteins as a means of stimulating antibody formation, we sought a procedure which would employ terminal nucleotide PO4 or OH groups for coupling. Two ways in which the terminal PO4 groups might be coupled covalently to protein would involve formation of a phosphodiester bond with protein seryl and threonyl residues or an N-P bond with protein ε-amino groups (Fig. 1, reactions 1 and 2 respectively). On the other hand, the OH group of a terminal sugar residue could react with protein carboxyl groups forming an ester (Fig. 1, reaction 3).
Expression of c-erbB-2 in Human Pancreatic Adenocarcinomas (1991)

The c-erbB-2 (neu) gene encodes a transmembrane phosphoglycoprotein (p185erbB-2) which resembles a growth factor receptor-like molecule closely related to the epidermal growth factor receptor. Overexpression of c-erbB-2 induces cell transformation in vitro. Poorer survival rates and elevated recurrence rates following treatment have been shown in patients whose breast adenocarcinomas demonstrate increased c-erbB-2 expression. Using immunoprecipitation and immunoperoxidase staining, we surveyed human cell lines for p185erbB-2. Cell lines from most tumor types (e.g. lymphomas, neuroblastomas, melanomas) demonstrated negligible p185erB-2; however, 3 of 6 pancreatic cell lines overexpressed c-erbB-2. Southern blot analysis revealed that c-erbB-2 was amplified in two of these cell lines and was both rearranged and amplified in one of them. Based on these findings, we examined tissue sections from archival specimens of primary human pancreatic adenocarcinomas. A substantial proportion of specimens had increased p185erbB-2, as judged by increased immunostaining of the tumor cells. In such pancreatic tumors p185erbB-2 may contribute to the malignant phenotype and could provide a target for immunodiagnostic or immunotherapeutic strategies.
Gold, Poly(β-amino ester) Nanoparticles for Small Interfering RNA Delivery (2009)

The safe and effective delivery of RNA therapeutics remains the major barrier to their broad clinical application. Here we develop a new nanoparticulate delivery system based on inorganic particles and biodegradable polycations. First, gold nanoparticles were modified with the hydrophilic polymer poly(ethylene glycol) (PEG), and then small interfering RNA (siRNA) was conjugated to the nanoparticles via biodegradable disulfide linkages, with approximately 30 strands of siRNA per nanoparticle. The particles were then coated with a library of end-modified poly(beta-amino ester)s (PBAEs), previously identified as capable of facilitating intracellular DNA delivery. Nanoparticulate formulations developed here facilitate high levels of in vitro siRNA delivery, facilitating delivery as good or better than the commercially available lipid reagent, Lipofectamine 2000.
Nucleotide Dimers as Anti Human Immunodeficiency Virus Agents (1989)

A series of nucleotide homo and heterdimers were synthesized from nucleosides which include azidothymidine, 2′, 3′-dideoxyadenosine and 2′3′-dideoxyinosine. The compounds were evaluated with respect to anti-HIV activity, cytotoxicity, in vitro stability and in vivo distribution. On an equimolar basis, greater anti-HIV potency and enhanced cytotherapeutic indices were obtained with heterodimers relative to the corresponding monomers. In vitro stability of the dimer phosphate linkage was found to be species dependent. After intravenous administration to rats, the distribution of 3′-azido-3′-3′-deoxythymidilyl-(5′5′)-2′,3′-dideoxy;-5′-adenylic acid, 2-cyanoethyl ester (AZT-P(CyE)ddA) and AZT in plasma and brain was similar. In 1981, the acquired immunodeficiency syndrome (AIDS) was reported as a new clinical entity (1-3). An intensive research effort led to the identification of the etiologic agent responsible for the disease. (4-7). The pathogen, human immunodeficiency virus (HIV), is a non-oncogenic retrovirus closely associated with the lentivirus family (8,9). The discovery of HIV led to the development of therapeutic strategies
Evaluation of the product based on Recaldent technology in the treatment of dentin hypersensitivity. (2006)

The aim of the study was to evaluate the efficiency of GC Tooth Mousse in the treatment of patients with dentin hypersensitivity caused by various factors.The evaluation was carried out on 101 teeth with dentin hypersensitivity in 13 patients. Patients with gingival recession and exposed dental necks and those with non-carious lesions at the initial stage were selected. The initial examination was to evaluate the intensity of pain inducted by a stream of the air syringe and by probing the tooth surface. It was repeated directly after the preparation application, after 15 minutes, after 1 and 4 weeks.After the medicine application, the number of teeth reacting with strong or extremely strong pain decreased (from almost 80% to 37.62%). The percentage of teeth reacting with mild pain increased by 15% and the number of teeth which did not react to the cold air stream also increased by 27.72%. The values after 15 minutes were similar. A week later, the percentage of teeth with very strong pain was elevated and so was the percentage of medium pain. On the other hand, the number of teeth without pain and with mild pain decreased twice. After one month the percentage distribution was close to the results obtained after 7 days.1. GC Tooth Mousse preparation, based on Recaldent technology reveals insufficient effectiveness and short-term therapeutic effect in treating hypersensitivity of dentine. 2. It seems that soothing the pain by GC Tooth Mousse should be regarded rather as an additional remineralizing effect of the medicine.
Monoclonal antibody (WT 1) directed against a T cell surface glycoprotein: characteristics and immunosuppressive activity. (1984)

WT 1, an IgG2a subclass monoclonal antibody, recognizes a human T lineage specific antigen (mol. wt 40,000). This antigen is strongly expressed on thymic T blasts, and on peripheral T cells activated by phytohaemagglutinin, whereas cortical thymocytes and peripheral T cells are moderately positive for WT 1. In contrast, B lymphocytes, myeloid and erythroid cells, including the progenitor cells of these lineages, and terminal deoxynucleotidyl transferase positive cells in the bone marrow, are all WT 1 negative. Binding of WT 1 to T cells is blocked by a previously described antibody (3A1) suggesting that both antibodies bind to the same antigen present on human T cells. WT 1, however, is also reactive with T lymphocytes from rhesus monkeys whereas 3A1 is not. Therefore, the biological effects of WT 1 could be studied in a monkey model. In a skin allograft model, WT 1 was immunosuppressive and induced a marked prolongation of graft survival.
Understanding the Molecule−Surface Chemical Coupling in SERS (2009)

The enhancement mechanism due to the molecule-surface chemical coupling in surface-enhanced Raman scattering (SERS) has been characterized using time-dependent density functional theory. This has been achieved with a systematical study of the chemical enhancement of meta- and para-substituted pyridines interacting with a small silver cluster (Ag(20)). Changing the functional groups on pyridine enabled us to modulate the direct chemical interactions between the pyridine ring and the metal cluster. Surprisingly, we find that the enhancement does not increase as more charge is transferred from the pyridine ring to the cluster. Instead, we find that the magnitude of chemical enhancement is governed to a large extent by the energy difference between the highest occupied energy level (HOMO) of the metal and the lowest unoccupied energy level (LUMO) of the molecule. The enhancement scales roughly as (omega(X)/omega(e))(4), where omega(e) is an average excitation energy between the HOMO of the metal and the LUMO of the molecule and omega(X) is the HOMO-LUMO gap of the free molecule. The trend was verified by considering substituted benzenethiols, small molecules, and silver clusters of varying sizes. The results imply that molecules that show significant stabilization of the HOMO-LUMO gaps (such as those that readily accept pi-backbonding) would be likely to have strong chemical enhancement. The findings presented here provide the framework for designing new molecules which exhibit high chemical enhancements. However, it remains a challenge to accurately describe the magnitude of the Raman enhancements using electronic structure methods, especially density functional theory, because they often underestimate the energy gap.
Emergent mechanistic diversity of enzyme-catalysed β-diketone cleavage (2005)

The enzymatic cleavage of C-C bonds in beta-diketones is, comparatively, a little studied biochemical process, but one that has important relevance to human metabolism, bioremediation and preparative biocatalysis. In recent studies, four types of enzymes have come to light that cleave C-C bonds in the beta-diketone functionality using different chemical mechanisms. OPH [oxidized poly(vinyl alcohol) hydrolase from Pseudomonas sp. strain VM15C], which cleaves nonane-4,6-dione to butyrate and pentan-2-one is a serine-triad hydrolase. Dke1 (diketone-cleaving enzyme from Acinetobacter johnsonii) is a dioxygenase, cleaving acetylacetone to methylglyoxal and acetate. Fumarylacetoacetate hydrolase cleaves fumarylacetoacetate to fumarate and acetoacetate using a water molecule, activated by a catalytic His/Asp dyad, aided by a calcium ion that both chelates the enol acid form of the substrate and indirectly positions the water for nucleophilic attack at a carbonyl group. 6-oxocamphor hydrolase cleaves nonenolizable cyclic beta-diketones and is a homologue of the crotonase superfamily, employing a catalytic His/Asp dyad to activate a water molecule for nucleophilic attack at a carbonyl group on one prochiral face of the diketone substrate, effecting desymmetrizations of symmetrical substrates.
Adeno-associated virus vectors; Gene therapy and viral vectors, the gap is closing (1999)

Conference Abstract| October 01 1999 Adeno-associated virus vectors; Gene therapy and viral vectors, the gap is closing Richard Jude Samulski, PhD Richard Jude Samulski, PhD 1Professor, Director Gene Therapy Center, CB 7352, Chapel Hill, NC 27599–7352 Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1999 Biochemical Society1999 Biochem Soc Trans (1999) 27 (5): A136. https://doi.org/10.1042/bst027a136c Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation Richard Jude Samulski; Adeno-associated virus vectors; Gene therapy and viral vectors, the gap is closing. Biochem Soc Trans 1 October 1999; 27 (5): A136. doi: https://doi.org/10.1042/bst027a136c Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1999 Biochemical Society1999 Article PDF first page preview Close Modal You do not currently have access to this content.
Cloning and heterologous expression in Streptomyces lividans of Streptomyces rimosus genes involved in oxytetracycline biosynthesis (1989)

The anhydrotetracycline (ATC) oxygenase enzyme which carries out the conversion of ATC to dehydrotetracycline was purified and the N-terminal amino acid sequence was determined. The sequence displays a significant similarity to that of the p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens. This is consistent with the activity of the oxygenase, i.e., addition of a hydroxyl moiety to an aromatic ring structure. Oligonucleotide probes were designed and used to clone the corresponding fragment of chromosomal DNA from Streptomyces rimosus. This DNA fragment was used to screen a cosmid library, allowing the isolation of flanking DNA sequences. Surprisingly, the gene was located within the previously cloned cluster of genes involved in the synthesis of the biosynthetic intermediate ATC and not as had been expected (P. M. Rhodes, N. Winskill, E. J. Friend, and M. Warren, J. Gen. Microbiol. 124:329-338, 1981) at a separate locus on the other side of the chromosome. Subcloning of an appropriate DNA fragment from one of the cosmid clones onto pIJ916 produced Streptomyces lividans transformants which synthesized oxytetracycline.
Estrogen Signaling: A Subtle Balance Between ER and ER (2003)

The biological actions of estrogens are mediated by estrogen binding to one of two specific estrogen receptors (ERs) ERalpha and ERbeta, which belong to the nuclear receptor superfamily, a family of ligand-regulated transcription factors. ERalpha and ERbeta are products of different genes and exhibit tissue- and cell-type specific expression. The characterization of mice lacking ERalpha, or ERbeta, or both has revealed that both receptor subtypes have overlapping but also unique roles in estrogen-dependent action in vivo. Additionally, ERalpha and ERbeta have different transcriptional activities in certain ligand, cell-type, and promoter contexts. Both receptors, however, are coexpressed in a number of tissues and form functional heterodimers. The biological roles of ERalpha /beta heterodimers in the presence of each respective homodimer are unknown. When coexpressed, ERbeta exhibits an inhibitory action on ERalpha -mediated gene expression and in many instances opposes the actions of ERalpha. A number of ERalpha and ERbeta isoforms have also been described, many of which alter estrogen-mediated gene expression. Uncovering the molecular mechanisms regulating the expression of both ERs, and how ERalpha and ERbeta directly or indirectly affect each other's function are paramount to understanding the cellular and biological events of estrogen-mediated gene regulation in normal and diseased tissues.
Calcium, vitamin D, and colorectal cancer: a review of the epidemiologic evidence. (1998)

A protective effect of calcium on colorectal cancer, one of the most common malignancies in Western societies, has been supported primarily by results of in vitro animal studies. The present review summarizes the available epidemiological evidence for the association between calcium, vitamin D, and colorectal cancer. The overall results from over 20 published case-control and cohort studies suggest that calcium intake is not associated with a substantially lower risk of colorectal cancer. Findings from large prospective cohort studies, which should be least affected by methodological bias, have been notably consistent in finding weak and nonsignificant inverse associations. Whereas the relation between calcium and colon or colorectal cancer has been studied in numerous epidemiological studies, the role of vitamin D has only been addressed in a few of these investigations. The available results for vitamin D suggest that this micronutrient is inversely associated with risk but, given the scarcity of data, additional studies are needed to investigate this relation in more detail.