gebhart/patrepeval huggingface dataset:
Role of B-ring of colchicine in its binding to tubulin. (1981)

The chemical specificity of the colchicine-binding site of tubulin is less stringent for the presence of the B-ring than the A- and C-rings of colchicine, Colchicine analogues with modifications in the B-ring bind to tubulin at the same site as colchicine. Analogues with smaller or no substituents in the B-ring bind tubulin remarkably faster than colchicine. Thus, a compound without the B-ring [2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone] binds tubulin even at 4 degrees C and the binding is almost instantaneous at 37 degrees C. Colcemid and 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone bind reversibly to tubulin, whereas colchicine and desacetamidocolchicine bind almost irreversibly, suggesting that the size of the B-ring moiety of colchicine is not related to the reversibility of binding. We conclude that although the presence of the B-ring of colchicine does not appear to be an essential prerequisite for the drug-tubulin interaction, the B-ring substituents play an important role in determining the binding properties of colchicine to tubulin.
Downregulation of PIK3CB by siRNA Suppresses Malignant Glioma Cell Growth In Vitro and In Vivo (2006)

EGFR overexpression is the most frequent and important molecular event in the development of astrocytic gliomas, and the P13K signaling pathway is one of the most important downstream pathways of EGFR. EGFR and other members of the receptor tyrosine kinases (RTKs) family, such as VEGFR, PDGFR, and IGFR, et cetera, are often overexpressed in most of malignant gliomas and share common downstream signaling pathways. Therefore, it is considered that directly targeting the downstream PI3K pathway may be more effective in blocking multiple inputs. The PIK3CB gene encoding the class 1A PI3K catalytic subunit p110beta was selected as the target of therapeutic approach for malignant gliomas in the present study. Human U251 glioblastoma cells with high endogenous p110beta expression were transfected with plasmid-based siRNA targeting PIK3CB gene. It was found that downregulation of p110beta expression resulted in the suppression of cell proliferation, arrest of cell cycle, reduction of cell invasion, and promotion of cell apoptosis in vitro. In addition, the growth of the subcutaneous U251 glioma in the nude mice treated with siRNA targeting PIK3CB was significantly inhibited. These results demonstrate that PIK3CB overexpression may play an oncogenic role in the PI3K pathway, and the plasmid-based siRNA targeting of PIK3CB is a potential and promising approach for the treatment of malignant gliomas.
Near-infrared Optical Imaging of Exposed Phosphatidylserine in a Mouse Glioma Model (2011)

Phosphatidylserine (PS) is normally intracellular but becomes exposed on the luminal surface of vascular endothelial cells in tumors. It also becomes exposed on tumors cells responding to therapy. In the present study, we optically imaged exposed PS in vivo using PGN635, a novel monoclonal antibody that binds PS. The F(ab')(2) fragment of PGN635 was labeled with the near-infrared (NIR) dye, IRDye800CW. In vivo dynamic NIR imaging was performed after injection of 800CW-PGN635 into mice bearing radiation-treated or untreated U87 glioma xenografts growing subcutaneously or orthotopically. NIR optical imaging revealed a clear tumor contrast in nonirradiated subcutaneous U87 gliomas after injection of 800CW-PGN635. The tumor contrast was visible as early as 4 hours later and was maximal 24 hours later (tumor-to-normal tissue ratio [TNR] = 2.8 ± 0.7). Irradiation enhanced the tumor contrast at 24 hours (TNR = 4.0 ± 0.3). Similar results were observed for orthotopic gliomas. Localization of 800CW-PGN635 to tumors was antigen specific because 800CW-Aurexis, a control probe of irrelevant specificity, did not localize to the tumors, and preadministration of unlabeled PGN635 blocked the uptake of 800CW-PGN635. Fluorescence microscopy confirmed that 800CW-PGN635 was binding to PS-positive vascular endothelial cells in nonirradiated gliomas. Irradiation of the gliomas increased PS exposure on both tumor vascular endothelial cells and tumor cells and gave rise to an increase in tumor contrast with 800CW-PGN635 that was predictive of the reduction in tumor growth. 800CW-PGN635 may be a useful new imaging probe for detection of exposed PS in tumors responding to therapy.
Growth-dependent expression of dihydrofolate reductase mRNA from modular cDNA genes. (1983)

Dihydrofolate reductase (DHFR) synthesis is regulated in a growth-dependent fashion. Dividing cells synthesize DHFR at a 10-fold-higher rate than do stationary cells. To study this growth-dependent synthesis. DHFR genes have been constructed from a DHFR cDNA segment, the adenovirus major late promoter, and fragments of simian virus 40 (SV40) which provide signals for polyadenylation. These genes have been introduced into Chinese hamster ovary cells. The DHFR mRNAs produced in different transformants are identical at their 5' ends, but differ in sequences in their 3' ends as different sites are utilized for polyadenylation. Three transformants that utilize either DHFR polyadenylation signals or the SV40 late polyadenylation signal exhibit growth-dependent DHFR synthesis. The level of DHFR mRNA in growing cells is approximately 10 times that in stationary cells for these transformants. This growth-dependent DHFR mRNA production probably results from posttranscriptional events. In contrast, three transformants that utilize the SV40 early polyadenylation signal and another transformant that utilizes a cellular polyadenylation signal do not exhibit growth-dependent DHFR synthesis. In these three cell lines, the fraction of mRNAs polyadenylated at different sites in a tandem array shifts between growing and stationary cells. These results suggest that the metabolic state of the cell is important in determining either the efficiency of polyadenylation at various sites or the stability of mRNA polyadenylated at various sites.
Fructose-1,6-Diphosphatase and Acid Hexose Phosphatase of Escherichia coli (1965)

Fraenkel, D. G. (Albert Einstein College of Medicine, New York, N.Y.), and B. L. Horecker. Fructose-1,6-diphosphatase and acid hexose phosphatase of Escherichia coli. J. Bacteriol. 90:837-842. 1965.-The conversion of fructose-1,6-diphosphate to fructose-6-phosphate (fructose-1,6-diphosphatase activity) is essential for growth of Escherichia coli on glycerol, acetate, or succinate, but is unnecessary for growth on hexoses or pentoses. It has sometimes been assumed that fructose-1,6-diphosphatase activity is due to a nonspecific acid hexose phosphatase. We have now obtained a number of one-step mutants which have lost the ability to grow on glycerol, succinate, or acetate, but which grow normally on hexoses; these mutants are deficient in a fructose-1,6-diphosphatase which can be assayed spectrophotometrically in the presence of Mg(++) and low concentrations of substrate. These mutants still possess the nonspecific acid hexose phosphatase, which does not require Mg(++) and is active only at much higher concentrations of fructose-1,6-diphosphate. Evidence is presented to support the hypothesis that the newly described activity is the physiological fructose-1,6-diphosphatase. The acid hexose phosphatase is a different enzyme whose function remains unknown.
A prostate antigen in sera of prostatic cancer patients. (1980)

A prostate antigen has been detected by a rocket immunoelectrophoresis technique in 17 of 219 sera obtained from patients with advanced prostatic cancer. Sera from 175 patients with nonprostatic cancers, including those with late-stage disease of the breast, lung, colon, rectum, stomach, and pancreas, were antigen negative as were 20 samples each from normal adults and age-matched males. Antigen in sera showed immunological identity with antigen in prostate tissue as determined by immunoprecipitation peak enhancement experiments. Using antibody affinity chromatography and radioimmunoprecipitation techniques, the antigen in sera was purified and subjected to sodium dodecyl sulfate electrophoresis; it exhibited a molecular weight of approximately 36,000, similar to that of antigen isolated from prostatic tissue.
Ileal Bile Acid Transporter Inhibition for the Treatment of Chronic Constipation, Cholestatic Pruritus, and NASH (2018)

Bile acids are synthesized from cholesterol in the liver, excreted with bile into the duodenum, almost completely taken up again in the distal ileum and finally returned to the liver with portal blood in a process termed enterohepatic circulation. Bile acid synthesis, excretion, and reuptake are tightly regulated. The apical sodium-dependent bile acid transporter [ASBT; also known as ileal bile acid transporter (IBAT) and SLC10A2] is pivotal for the almost complete reabsorption of conjugated bile acids in the ileum. Dysfunctional IBAT may be the cause of bile acid diarrhea. Pharmacological IBAT inhibition results in an increased bile acid load in the colon and subsequently a lower bile acid pool, which is associated with improved liver histology in animal models of cholestatic liver disease and non-alcoholic steatohepatitis (NASH). In humans, IBAT inhibitors have been tested in clinical trials with widely different indications: in patients with idiopathic chronic constipation, an increased number of bowel movements was observed. In adult and pediatric cholestatic liver diseases with pruritus, various IBAT inhibitors showed potential to improve itching. Adverse events of IBAT inhibitors, based on their mode of action, are abdominal pain and diarrhea which might patients to withdraw from study medications. So far, no data are available of a study of IBAT inhibitors in patients with NASH. In this review we summarize the preclinical and most recent clinical studies with various IBAT inhibitors and discuss the difficulties that should be addressed in future studies.
Teicoplanin: chemical, physico-chemical and biological aspects. (1987)

The structure determination and the physico-chemical properties of teicoplanin, a new glycopeptide antibiotic of the vancomycin-ristocetin family are presented. Some biological studies and the mechanism of action at the molecular level are discussed. Analytical test methods, such as HPLC assay, bioassay and enzymatic assay are described. The antimicrobial activity of teicoplanin and of some relevant acid and basic hydrolysis products are also discussed.
p185neu expression in human lung adenocarcinomas predicts shortened survival. (1990)

p185neu is the protein product of the HER2/neu protooncogene. This protein has characteristics of a tyrosine kinase growth factor receptor and is postulated to be important in human carcinogenesis. To define the significance of the expression of this protein in human non-small cell lung cancer, 55 tumors from patients with squamous cell carcinoma (16), adenocarcinoma (29), or large cell carcinoma (10) of the lung were examined for p185neu using immunohistological methods. Five of 16 squamous cell carcinomas and 10 of 29 adenocarcinomas were found to overexpress p185neu relative to levels of expression seen in uninvolved bronchiolar epithelium. For the adenocarcinomas, p185neu expression was associated with older age (66.6 +/- 10.1 versus 57.5 +/- 10.8 years) (P = 0.04) and shortened survival (83.7 +/- 94.1 versus 188.5 +/- 120 weeks) (P = 0.01). In this group, using Cox's multivariate survival analysis, p185neu expression was found to be a significant determinant of survival (P = 0.04) even after accounting for the effect of tumor stage. For the squamous cell carcinomas, p185neu expression was not correlated with any of our clinicopathological parameters. Our findings indicate that non-small cell lung cancers which express p185neu do so at levels higher than that found in normal bronchiolar epithelium, and expression in adenocarcinomas of the lung is independently associated with diminished survival intervals.
PD-L1 regulates the development, maintenance, and function of induced regulatory T cells (2009)

Both the programmed death (PD) 1-PD-ligand (PD-L) pathway and regulatory T (T reg) cells are instrumental to the maintenance of peripheral tolerance. We demonstrate that PD-L1 has a pivotal role in regulating induced T reg (iT reg) cell development and sustaining iT reg cell function. PD-L1(-/-) antigen-presenting cells minimally convert naive CD4 T cells to iT reg cells, showing the essential role of PD-L1 for iT reg cell induction. PD-L1-coated beads induce iT reg cells in vitro, indicating that PD-L1 itself regulates iT reg cell development. Furthermore, PD-L1 enhances and sustains Foxp3 expression and the suppressive function of iT reg cells. The obligatory role for PD-L1 in controlling iT reg cell development and function in vivo is illustrated by a marked reduction in iT reg cell conversion and rapid onset of a fatal inflammatory phenotype in PD-L1(-/-)PD-L2(-/-) Rag(-/-) recipients of naive CD4 T cells. PD-L1 iT reg cell development is mediated through the down-regulation of phospho-Akt, mTOR, S6, and ERK2 and concomitant with the up-regulation of PTEN, all key signaling molecules which are critical for iT reg cell development. Thus, PD-L1 can inhibit T cell responses by promoting both the induction and maintenance of iT reg cells. These studies define a novel mechanism for iT reg cell development and function, as well as a new strategy for controlling T reg cell plasticity.
The physiology of the cerebrovascular parasympathetic innervation (1995)

The parasympathetic innervation to the cerebral vessels has only recently begun to be investigated in detail and to be understood in terms of the control of brain function. Much of the experimental work has been motivated by the potent vasoactive potential of the parasympathetic fibres, which can produce profound increases in cerebral blood flow (CBF) when electrically stimulated. This paper first outlines the principal anatomical and biochemical evidence for the origins and pathways of the parasympathetic fibres and the basis of their influence on CBF. Next, studies performed to elucidate their physiological function are reviewed, and finally their possible functional significance is discussed in relation to normal and pathophysiological brain function and their possible involvement in the trigeminovascular system.
Physiological Phenotype and Vulnerability in Parkinson's Disease (2012)

This review will focus on the principles underlying the hypothesis that neuronal physiological phenotype-how a neuron generates and regulates action potentials-makes a significant contribution to its vulnerability in Parkinson's disease (PD) and aging. A cornerstone of this hypothesis is that the maintenance of ionic gradients underlying excitability can pose a significant energetic burden for neurons, particularly those that have sustained residence times at depolarized membrane potentials, broad action potentials, prominent Ca(2+) entry, and modest intrinsic Ca(2+) buffering capacity. This energetic burden is shouldered in neurons primarily by mitochondria, the sites of cellular respiration. Mitochondrial respiration increases the production of damaging superoxide and other reactive oxygen species (ROS) that have widely been postulated to contribute to cellular aging and PD. Many of the genetic mutations and toxins associated with PD compromise mitochondrial function, providing a mechanistic linkage between known risk factors and cellular physiology that could explain the pattern of pathology in PD. Because much of the mitochondrial burden created by this at-risk phenotype is created by Ca(2+) entry through L-type voltage-dependent channels for which there are antagonists approved for human use, a neuroprotective strategy to reduce this burden is feasible.
Gap-Dependent Optical Coupling of Single “Bowtie” Nanoantennas Resonant in the Visible (2004)

Metallic “bowtie” nanoantennas consisting of two opposing tip-to-tip Au triangles have been fabricated with triangle lengths of 75 nm and gaps ranging from 16 to 488 nm. For light polarized along the line between the two triangles, the plasmon scattering resonance first blue-shifts with increasing gap, and then red-shifts as the particles become more and more uncoupled, while perpendicularly polarized excitation shows little dependence upon gap size. This behavior may be approximately understood in a coupled-dipole approximation as changes in the phase between static dipole−dipole interactions and dipole radiative interaction effects.
The Hek Outer Membrane Protein of Escherichia coli Strain RS218 Binds to Proteoglycan and Utilizes a Single Extracellular Loop for Adherence, Invasion, and Autoaggregation (2007)

Escherichia coli is the principal gram-negative causative agent of sepsis and meningitis in neonates. The pathogenesis of meningitis due to E. coli K1 involves mucosal colonization, transcytosis of epithelial cells, survival in the bloodstream, and eventually invasion of the meninges. The last two aspects have been well characterized at a molecular level. Less is known about the early stages of pathogenesis, i.e., adhesion to and invasion of epithelial cells. We have previously reported that the Hek protein causes autoaggregation and can mediate adherence to and invasion of epithelial cells. Here, we report that Hek-mediated adherence is dependent on binding to glycosoaminoglycan, in particular, heparin. The ability to hemagglutinate, autoaggregate, adhere, and invade is contingent on a putative 25-amino-acid loop that is exposed to the outside of the bacterial cells.
Enzyme Level Changes in the Cerebrospinal Fluid of Patients With Acute Stroke (1986)

Creatine kinase (CK), brain CK (CKBB), lactate dehydrogenase (LD), and aspartate aminotransferase (ASAT) levels were determined in cerebrospinal fluid (CSF) obtained from 35 patients with acute stroke. In patients with transient, minor neurological disturbances, only LD levels increased; in those who remained comatose and died, the levels of all the enzymes, except ASAT, increased. Patients who remained with focal motor defects had increased CK and LD levels, while CKBB and ASAT levels were variable. In most of the CSF samples, muscle CK activity was also detectable, suggestive of a leakage from blood to CSF. The pattern of the enzyme increase could be related to the causative mechanisms for the strokes. The study suggests that CSF enzyme determinations may provide supplementary information as to the extent and severity of brain damage and the recovery potentials of selected patient groups with strokes.
Coded multi-angular illumination for Fourier ptychography based on Hadamard codes (2015)

Fourier ptychographic microscopy (FPM) is a newly developed super-resolution technique, which employs angularly varying illumination and a phase retrieval algorithm to surpass the diffraction limit of the objective lens. Specifically, FP captures a set of low-resolution (LR) images, under angularly varying illuminations, and stitches them together in the Fourier domain. However, because the requisite large number of incident illumination angles, the long capturing process becomes an obvious limiting factor. Furthermore, in order to acquire high-dynamic range images, the time can be increased several times over. In this work, utilizing the Hadamard code principle, we propose a highly efficient method, which applies coded multi-angular illumination for FPM, to shorten the exposure time of each raw image. High acquisition efficiency is achieved by employing an optimal multi-angular illumination scheme by using two set of Hadamard coded multiplexing patterns. Both simulation and experimental results indicate that the proposed multi-angular illumination process could shorten the acquisition time of conventional FPM.
Novel Biotin Phosphoramidites with Super-long Tethering Arms (2003)

A number of novel biotin phosphoramidites, possessing exceptionally long and uncharged tethering arms, were synthesized from methoxyoxalamido (MOX) and succinimido (SUC) precursors. Included among these monomers is a uridine derivative with the biotin moiety attached through the 2'-position. Some of these phosphoramidites were used to make 5'-biotinylated primers, which were applied in direct sequencing of genomic DNA and capture of Sanger fragment pools.
Distamycin and Penta-N-Methylpyrrolecarboxamide Binding Sites on Native DNA A Comparison of Methidiumproyl-EDTA-Fe(II) Footprinting and DNA Affinity Cleaving (1984)

Using two direct methods we have studied the binding locations and site sizes of distamycin and penta-N-methylpyrrolecarboxamide on three DNA restriction fragments from pBR322 plasmid. We find that methidiumpropyl-EDTA.Fe(II) footprinting and DNA affinity cleaving methods report common binding locations and site sizes for the tri- and pentapeptides bound to heterogeneous DNA. The tripeptide distamycin binds 5-base-pair sites with a preference for poly(dA).poly(dT) regions. The pentapeptide binds 6-7-base-pair sites with a preference for poly(dA).poly(dT) regions. These results are consistent with distamycin binding as an isogeometric helix to the minor groove of DNA with the four carboxamide N-H's hydrogen bonding five A + T base pairs. The data supports a model where each of the carboxamide N-H's can hydrogen bond to two bases, either O(2) of thymine or N(3) of adenine, located on adjacent base pairs on opposite strands of the helix. In most (but not all) cases the tri- and pentapeptide can adopt two orientations at each A + T rich binding site.
Bacterial interspersed mosaic elements (BIMEs) are present in the genome of Klebsiella (1993)

Bacterial interspersed mosaic elements (BIMEs) constitute a family of highly repetitive sequences containing palindromic units (PUs), also called repetitive extragenic palindromes (REPs). BIMEs were originally described in Escherichia coli and Salmonella typhimurium. We show here, by determining the nucleotide sequence of two intergenic regions of Klebsiella pneumoniae, by computer searches, and by hybridization, that sequences with similar characteristics are found in the genome of several Klebsiella species. This reinforces the idea that BIMEs play general and important roles in enterobacteria such as in the organization of the bacterial chromosome.
A microRNA signature for a BMP2-induced osteoblast lineage commitment program (2008)

Bone morphogenetic proteins (BMPs) are potent morphogens that activate transcriptional programs for lineage determination. How BMP induction of a phenotype is coordinated with microRNAs (miRNAs) that inhibit biological pathways to control cell differentiation, remains unknown. Here, we show by profiling miRNAs during BMP2 induced osteogenesis of C2C12 mesenchymal cells, that 22 of 25 miRNAs which significantly changed in response to BMP2 are down-regulated. These miRNAs are each predicted to target components of multiple osteogenic pathways. We characterize two representative miRNAs and show that miR-133 directly targets Runx2, an early BMP response gene essential for bone formation, and miR-135 targets Smad5, a key transducer of the BMP2 osteogenic signal, controlled through their 3'UTR sequences. Both miRNAs functionally inhibit differentiation of osteoprogenitors by attenuating Runx2 and Smad5 pathways that synergistically contribute to bone formation. Although miR-133 is known to promote MEF-2-dependent myogenesis, we have identified a second complementary function to inhibit Runx2-mediated osteogenesis. Our key finding is that BMP2 controls bone cell determination by inducing miRNAs that target muscle genes but mainly by down-regulating multiple miRNAs that constitute an osteogenic program, thereby releasing from inhibition pathway components required for cell lineage commitment. Thus, our studies establish a mechanism for BMP morphogens to selectively induce a tissue-specific phenotype and suppress alternative lineages.