gebhart/patrepeval huggingface dataset:
Tetrahydrogestrinone Is an Androgenic Steroid that Stimulates Androgen Receptor-Mediated, Myogenic Differentiation in C3H10T1/2 Multipotent Mesenchymal Cells and Promotes Muscle Accretion in Orchidectomized Male Rats (2005)

The discovery of tetrahydrogestrinone (THG) abuse by several elite athletes led the U.S. Congress to declare it a controlled substance, although conclusive evidence of its anabolic/androgenic activity is lacking. We determined whether THG affects myogenic differentiation and androgen receptor (AR)-mediated signaling, whether it binds to AR, and whether it has androgenic and anabolic effects in vivo. Accordingly, we measured the dissociation constant for THG with a fluorescence anisotropy assay using recombinant AR-ligand binding domain. The AR nuclear translocation and myogenic activity of androstenedione were evaluated in mesenchymal, multipotent C3H10T1/2 cells. We performed molecular modeling of the THG:AR interaction. The androgenic/anabolic activity was evaluated in orchidectomized rats. THG bound to AR with an affinity similar to that of dihydrotestosterone. In multipotent C3H10T1/2 cells, THG upregulated AR expression, induced AR nuclear translocation, dose dependently increased the area of myosin heavy chain type II-positive myotubes, and up-regulated myogenic determination and myosin heavy chain type II protein expression. The interaction between AR and the A ring of THG was similar to that between AR and the A ring of dihydrotestosterone, but the C17 and C18 substituents in THG had a unique stabilizing interaction with AR. THG administration prevented the castration-induced atrophy of levator ani, prostate gland, and seminal vesicles and loss of fat-free mass in orchidectomized rats. We conclude that THG is an anabolic steroid that binds to AR, activates AR-mediated signaling, promotes myogenesis in mesenchymal multipotent cells, and has anabolic and androgenic activity in vivo. This mechanism-based approach should be useful for rapid screening of anabolic/androgenic agents.
Induction of PD-L1 Expression by the EML4–ALK Oncoprotein and Downstream Signaling Pathways in Non–Small Cell Lung Cancer (2015)

Our findings that both EML4-ALK and mutant EGFR upregulate PD-L1 by activating PI3K-AKT and MEK-ERK signaling pathways in NSCLC reveal a direct link between oncogenic drivers and PD-L1 expression.
Induction of apoptosis by apicidin, a histone deacetylase inhibitor, via the activation of mitochondria-dependent caspase cascades in human Bcr-Abl-positive leukemia cells. (2003)

These results indicate that apicidin effectively induces the apoptosis of Bcr-Abl-positive leukemia cells through the activation of the mitochondrial pathway-dependent caspase cascades. The down-regulation of Bcr-Abl mRNA might also be one of the mechanisms implicated in the apicidin-mediated apoptosis in the K562 cells. This study provides the rationale to additionally investigate apicidin as a potential therapeutic agent for the drug-resistant Bcr-Abl-positive leukemia cells.
Hepatitis B virus gene function: the precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen. (1986)

The core gene of the hepatitis B virus genome contains two conserved in-phase initiation codons separated by about 90 nucleotides. This region ("the precore region") encodes largely hydrophobic amino acids. We have expressed the coding sequence of the core gene with or without the precore region by using a simian virus 40-derived vector in heterologous mammalian cells. The results show that the precore region is not required for the expression either of core antigen (cAg) or of a related hepatitis B virus antigen, the e antigen (eAg). However, the precore region causes the cAg to become associated with cytoplasmic membranes, probably the endoplasmic reticulum. Further, the presence of the precore sequence results in the secretion of eAg. Our results suggest that the precore region plays a role in targeting core proteins to the membrane; this may be the direct cause of eAg secretion and also may aid in the interaction of the core and surface antigens in the formation of the viral particle.
The CAG and GGC microsatellites of the androgen receptor gene are in linkage disequilibrium in men with prostate cancer. (1995)

The androgen receptor genotype was determined in the white blood cell DNA of 45 African-American, 39 non-Hispanic white, and 39 Asian (Chinese, Japanese) normal subjects and 68 patients with prostate cancer (57 whites), all of whom were residents of Los Angeles County. For each subject, we measured the number of repeats in the polymorphic CAG and GGC microsatellites of exon 1 of the androgen receptor gene. In normal subjects, the distributions of CAG and GGC microsatellites differed significantly among the races (two-sided P = 0.046 and < 0.0005, respectively). The prevalence of short CAG alleles (< 22 repeats) was highest (75%) in African-American males with the highest risk for prostate cancer, intermediate (62%) in intermediate-risk non-Hispanic whites, and lowest (49%) in Asians at very low risk for prostate cancer. High-risk African-Americans also had the lowest frequency (20%) of the GGC allele with 16 repeats; the comparable values for intermediate-risk whites and low-risk Asians were 57% and 70%, respectively. Consistent with the interracial variation in CAG and GGC distributions, there was an excess of white patients with < 22 CAG and not-16 GGC repeats relative to white controls (relative risk, 2.1; one-sided P = 0.08). We observed no association (linkage) between the two microsatellites among normal subjects. On the other hand, there was a statistically significant negative association between the numbers of CAG and GGC repeats among the prostate cancer patients studied (two-sided P = 0.008). Among the 47 subjects with short CAG alleles (< 22 repeats), 43% had long GGC alleles (> 16 repeats) whereas only 15% of the 20 subjects with long CAG alleles (> or = 22 repeats) had long GGC alleles. Overall, our data suggest a possible association between CAG and GGC microsatellites of the androgen receptor gene and prostate cancer development.
Mucosal Immunisation: Adjuvants and Delivery Systems (2004)

The mucosal administration of vaccines is an area currently receiving a high level of interest due to potential advantages offered by this technique. These advantages include the ability to administer vaccines without need for needles, thus improving patient compliance with vaccination schedules, and the capacity to induce immune responses capable of preventing infections at the site of acquisition. Despite these advantages a number of limitations exist which currently inhibit our ability to successfully develop new mucosal vaccines. As such, much research is currently focused on developing new adjuvants and delivery systems to overcome these difficulties. However, despite high levels of interest in this area, relatively few mucosal vaccine candidates have successfully progressed to human clinical trials. In the review that follows, we aim to provide the reader with an overview of the immune system with respect to induction of mucosal immune responses. Furthermore, the review provides an overview of a number of microbial (bacterial toxins, CpG DNA, cytokines/chemokines, live vectors, and virus like particles) and synthetic (microspheres, liposomes, and lipopeptides) strategies that have been investigated as adjuvants or delivery systems for mucosal vaccine development, with a focus on the delivery of vaccines via the oral route.
Reexpression of poly(sialic acid) units of the neural cell adhesion molecule in Wilms tumor. (1988)

A unique structural feature of the neural cell adhesion molecule N-CAM is the presence of homopolymers of alpha (2----8)-linked sialic acid units. We have used two specific probes for the detection of poly(sialic acid) in normal human kidney and Wilms tumor: a monoclonal antibody against meningococci group B capsular polysaccharide (homopolymers of alpha (2----8)-linked sialic acid units), which shows no crossreactivity with polynucleotides and denaturated DNA, and bacteriophage-induced endosialidases specifically hydrolyzing alpha (2----8)-linked poly(sialic acid) units. Additionally, for the detection of N-CAM, antibodies recognizing the polypeptide portion of the molecule and biotinylated antisense RNA transcribed from a cDNA clone for N-CAM were applied. Poly(sialic acid) was regionally detectable in human embryonic kidney but undetectable in normal adult kidney, as already reported for rat kidney. The malignant Wilms tumor, which is characterized by the presence of structural components resembling those found in embryonic kidney, reexpressed poly(sialic acid) units and showed positive immunostaining for the polypeptide portion of N-CAM. Immunoblot analysis of Wilms tumor as well as human embryonic kidney and brain with the monoclonal anti-poly(sialic acid) antibody revealed in each case the same high molecular mass broad band. In situ hybridization demonstrated the presence of mRNA for N-CAM in Wilms tumor. We conclude that poly(sialic acid), most probably present on N-CAM, is an oncodevelopmental antigen in human kidney.
ABSTRACT: Reservoir Modeling Using Multiple-Point Statistics (2002)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Inheritance of Resistance to Downy Mildew (Peronospora destructor [Berk.] Casp.) from Allium roylei Stearn in the Backcross Allium cepa L. × (A. roylei ×A. cepa) (1990)

Abstract Allium roylei Stearn and both reciprocals of the interspecific hybrid between Allium cepa L. and A. roylei displayed no symptoms of Peronospora destructor (Berk.) Casp. after artificial or natural inoculations, whereas A. cepa was susceptible. In the offspring from the backcross A. cepa × (A. roylei × A. cepa ) resistant and susceptible plants segregated after artificial inoculations, fitting a 1: 1‐ratio. This suggests that resistance is controlled by a single, dominantly‐inherited locus (designated Pd 1 ) from the nuclear genome of A. roylei. During a severe epidemic in the field, plants from the same backcross segregated resistant and susceptible individuals in a 3: 1‐ratio. Escapes may explain the deviation from the 1: 1‐segregation, but the presence of a second resistance locus segregating independently from Pd 1 cannot be excluded, implicating possible differences in virulence between populations of P. destructor. The occurrence in the backcross offspring of plants having a morphology similar to A. cepa without showing symptoms of downy mildew opens perspectives for breeding P. destructor ‐resistant onion varieties.
A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy (2009)

Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. Most SMA cases are associated with the low levels of SMN owing to deletion of Survival Motor Neuron 1 (SMN1). SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of SMN1 due to predominant skipping of exon 7. Hence, correction of aberrant splicing of SMN2 exon 7 holds the potential for cure of SMA. Here we report an 8-mer antisense oligonucleotide (ASO) to have a profound stimulatory response on correction of aberrant splicing of SMN2 exon 7 by binding to a unique GC-rich sequence located within intron 7 of SMN2. We confirm that the splicing-switching ability of this short ASO comes with a high degree of specificity and reduced off-target effect compared to larger ASOs targeting the same sequence. We further demonstrate that a single low nanomolar dose of this 8-mer ASO substantially increases the levels of SMN and a host of factors including Gemin 2, Gemin 8, ZPR1, hnRNP Q and Tra2-beta1 known to be down-regulated in SMA. Our findings underscore the advantages and unmatched potential of very short ASOs in splicing modulation in vivo.
Antitumor activity of lysophosphatidic acid acyltransferase-beta inhibitors, a novel class of agents, in multiple myeloma. (2003)

In this study, we examined the effects of isoform-specific functional inhibitors of lysophosphatidic acid acyltransferase (LPAAT), which converts lysophosphatidic acid to phosphatidic acid, on multiple myeloma (MM) cell growth and survival. The LPAAT-beta inhibitors CT-32176, CT-32458, and CT-32615 induced >95% growth inhibition (P < 0.01) in MM.1S, U266, and RPMI8226 MM cell lines, as well as MM cells from patients (IC(50), 50-200 nM). We further characterized this LPAAT-beta inhibitory effect using CT-32615, the most potent inhibitor of MM cell growth. CT-32615 triggered apoptosis in MM cells via caspase-8, caspase-3, caspase-7, and poly (ADP-ribose) polymerase cleavage. Neither interleukin 6 nor insulin-like growth factor I inhibited CT-32615-induced apoptosis. Dexamethasone and immunomodulatory derivatives of thalidomide (IMiDs), but not proteasome inhibitor PS-341, augmented MM cell apoptosis triggered by LPAAT-beta inhibitors. CT-32615-induced apoptosis was associated with phosphorylation of p53 and c-Jun NH(2)-terminal kinase (JNK); conversely, JNK inhibitor SP600125 and dominant-negative JNK inhibited CT-32615-induced apoptosis. Importantly, CT-32615 inhibited tumor necrosis factor-alpha-triggered nuclear factor-kappaB activation but did not affect either tumor necrosis factor-alpha-induced p38 mitogen-activated protein kinase phosphorylation or interleukin 6-triggered signal transducers and activators of transcription 3 phosphorylation. Finally, although binding of MM cells to bone marrow stromal cells augments MM cell growth and protects against dexamethasone-induced apoptosis, CT-32615 induced apoptosis even of adherent MM cells. Our data therefore demonstrate for the first time that inhibiting LPAAT-beta induces cytotoxicity in MM cells in the bone marrow milieu, providing the framework for clinical trials of these novel agents in MM.
The Immunomodulating Effects of Ganoderma lucidum (Curt.: Fr.) P. Karst. (Ling Zhi, Reishi Mushroom) (Aphyllophoromycetideae) (2002)

This review highlights the recent research progress in the study of immunomodulating effects of Ganoderma lucidum (Curt.: Fr.) P. Karst. (reishi. mushroom), which belongs to the higher Basidiomycetes. Several major substances with potent immunomodulating action have been isolated. These include polysaccharides (in particular b-D-glucans), proteins, and triterpenoids. The major immunomodulating effects of these active substances derived from G. lucidum include mitogenicity and activation of immune effector cells, such as Т cells, macrophages, and natural killer cells, resulting in the production of cytokines, including interleukins, tumor necrosis factor-d, and interferons. There is evidence indicating that b-D-glucans from medicinal mushrooms induce biological response by binding to membrane complement receptor type 3 (CR3, aMb2 integrin, or CD11b/CD18) on immune effector cells. The ligand-receptor complex can be internalized and activate nuclear factor NF-kВ. Immunosuppressive effects of G. lucidum components have also been observed. The therapeutic effects of G. lucidum, such as anticancer and antiinflammatory actions, have been associated with its immunomodulating effects. However, further studies are needed to determine the molecular mechanisms of the immunomodulating effects of G. lucidum.
Lignin: Genetic Engineering and Impact on Pulping (2003)

Lignin is a major component of wood, the most widely used raw material for the production of pulp and paper. Although the biochemistry and molecular biology underpinning lignin production are better understood than they are for the other wood components, recent work has prompted a number of re-evaluations of the lignin biosynthetic pathway. Some of the work on which these revisions have been based involved the investigation of transgenic plants with modified lignin biosynthesis. In addition to their value in elucidating the lignin biosynthetic pathway, such transgenic plants are also being produced with the aim of improving plant raw materials for pulp and paper production. This review describes how genetic engineering has yielded new insights into how the lignin biosynthetic pathway operates and demonstrates that lignin can be improved to facilitate pulping. The current technologies used to produce paper are presented in this review, followed by a discussion of the impact of lignin modification on pulp production. Fine-tuned modification of lignin content, composition, or both is now achievable and could have important economic and environmental benefits.
Does the Concentration, Isolation, or Deflavoring of Pea, Lentil, and Faba Bean Protein Alter Protein Quality? (2017)

Protein quality is the characteristic of a protein source that satisfies the requirements for growth and maintenance. Although there is interest in alternatives to animal-based protein, the plant-based alternatives currently available require significant processing prior to human consumption. Certain processes, including protein concentration, isolation, and deflavoring, have direct applications for product development because the processed compounds are high in protein. These processes, however, can alter the quality of the protein produced by changing the amino acid composition or altering the digestibility of the protein. This article provides an overview that describes the effects the techniques of protein concentration, isolation, and deflavoring have on the protein quality of three pulse classes: pea, lentil, and faba bean.
Characterization of the cell surface receptor for a multi-lineage colony-stimulating factor (CSF-2 alpha). (1986)

125I-Labeled colony-stimulating factor (CSF) 2 alpha (interleukin 3, multi-CSF, and mast cell growth factor) was used to characterize receptors specific for this lymphokine on the cell surface of the factor-dependent cell line FDC-P2. CSF-2 alpha binding to these cells was specific and saturable. Among a panel of lymphokines and growth factors, only unlabeled CSF-2 alpha was able to compete for the binding of 125I-labeled CSF-2 alpha to cells. Equilibrium binding studies revealed that CSF-2 alpha bound to 434 +/- 281 receptors/cell with a Ka of 8.7 +/- 3.9 X 10(9) M-1. Affinity cross-linking experiments with the homobifunctional cross-linking reagents disuccinimidyl suberate, disuccinimidyl tartrate, and dithiobis(succinimidyl propionate) produced a radiolabeled band of Mr = 97,000 on intact cells and in purified cell membranes, while an additional band of Mr = 138,000 was produced upon cross-linking to intact cells only. The relationship between these two bands is discussed. The results indicate that the receptor for CSF-2 alpha on FDC-P2 cells consists at a minimum of a subunit of Mr = 72,500.
Design and synthesis of 2-amino-6-(1H,3H-benzo[de]isochromen-6-yl)-1,3,5-triazines as novel Hsp90 inhibitors (2013)

A novel series of 2-amino-1,3,5-triazines bearing a tricyclic moiety as heat shock protein 90 (Hsp90) inhibitors is described. Molecular design was performed using X-ray cocrystal structures of the lead compound CH5015765 and natural Hsp90 inhibitor geldanamycin with Hsp90. We optimized affinity to Hsp90, in vitro cell growth inhibitory activity, water solubility, and liver microsomal stability of inhibitors and identified CH5138303. This compound showed high binding affinity for N-terminal Hsp90α (Kd=0.52nM) and strong in vitro cell growth inhibition against human cancer cell lines (HCT116 IC50=0.098μM, NCI-N87 IC50=0.066μM) and also displayed high oral bioavailability in mice (F=44.0%) and potent antitumor efficacy in a human NCI-N87 gastric cancer xenograft model (tumor growth inhibition=136%).
Integrated detection of both 5-mC and 5-hmC by high-throughput tag sequencing technology highlights methylation reprogramming of bivalent genes during cellular differentiation (2013)

5-methylcytosine (5-mC) can be oxidized to 5-hydroxymethylcytosine (5-hmC). Genome-wide profiling of 5-hmC thus far indicates 5-hmC may not only be an intermediate form of DNA demethylation but could also constitute an epigenetic mark per se. Here we describe a cost-effective and selective method to detect both the hydroxymethylation and methylation status of cytosines in a subset of cytosines in the human genome. This method involves the selective glucosylation of 5-hmC residues, short-Sequence tag generation and high-throughput sequencing. We tested this method by screening H9 human embryonic stem cells and their differentiated embroid body cells, and found that differential hydroxymethylation preferentially occurs in bivalent genes during cellular differentiation. Especially, our results support hydroxymethylation can regulate key transcription regulators with bivalent marks through demethylation and affect cellular decision on choosing active or inactive state of these genes upon cellular differentiation. Future application of this technology would enable us to uncover the status of methylation and hydroxymethylation in dynamic biological processes and disease development in multiple biological samples.
First evidence of spontaneous deamidation of glutamine residue via cyclic imide to α- and γ-glutamic residue under physiological conditions (1991)

At 37 °C and pH 7.4 the spontaneous deamidation of Gln-peptide proceeds prevalently via a glutarimide intermediate and gives a mixture of α-Glu- and γ-Glu-peptide.
A thiol-specific antioxidant and sequence homology to various proteins of unknown function. (1994)

Yeast and mammalian cells contain a 25 kDa enzyme that protects cellular components against oxidative damage from a system capable of generating reactive sulfur species, but not from a system that generates only reactive oxygen species. Yeast and rat cDNAs corresponding to this thiol-specific antioxidant (TSA) have been cloned and sequenced. Rat TSA is 65.3% identical and 76.2% similar to yeast TSA in amino acid sequence. A search of the GenBank database revealed 12 additional TSA-like proteins, which show sequence identity to rat TSA ranging from 31 to 76%. Except for the AhpC protein identified in Salmonella typhimurium, none of the TSA-like proteins is associated with known cellular functions. AhpC, which exhibits approximately 40% sequence identity to TSA, has been proposed to be a catalytic component of alkyl hydroperoxide reductase. Alignment of rat and yeast TSA with the TSA-like sequences revealed two conserved cysteine residues, one conserved in all 14 sequences and the other in 12 sequences. The most conserved cysteine is located in a well-conserved motif of (hydrophobic residue)6-Pro-non-conserved-residue-Asp-Phe-Thr-Phe-Val-Cys-Pro-Thr-Glu- hydrophobic residue. These results suggest that the TSA-like proteins of previously unknown function may represent a widely distributed family of antioxidants with functions similar to those of TSA and AhpC.