Miracle-dz/UniFAR-FTUs huggingface dataset:
FAK and p53 Synergistically Decrease Neuroblastoma Cell Survival

Neuroblastoma is the most common extracranial solid tumor of childhood and is responsible for over 15% of pediatric cancer deaths. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is important in many facets of neuroblastoma tumor development and progression. The p53 oncogene, although wild type in most neuroblastomas, lacks significant function as a tumor suppressor in these tumors. Recent reports have found that FAK and p53 interact in some tumor types. We have hypothesized FAK and p53 coordinately control each other’s expression and also interact in neuroblastoma. In the current study, we showed that not only do FAK and p53 interact but each one controls the expression of the other. In addition, we also examined the effects of FAK inhibition combined with p53 activation in neuroblastoma and showed that these two, in combination, had a synergistic effect upon neuroblastoma cell survival. The findings from this current study help to further our understanding of the regulation of neuroblastoma tumorigenesis, and may provide novel therapeutic strategies and targets for neuroblastoma and other pediatric solid tumors.
A search for AMD risk variants in Alzheimer disease genes and pathways

Several lines of inquiry point to overlapping molecular mechanisms between late-onset Alzheimer disease (AD) and age-related macular degeneration (AMD). We evaluated summarized results from large genome-wide association studies (GWAS) for AD and AMD to test the hypothesis that AD susceptibility loci are also associated with AMD. We observed association of both disorders with genes in a region of chromosome 7 including PILRA, and ZCWPW1 (peak AMD SNP rs7792525, MAF=19%, OR=1.14, p=2.34×10−6), and with ABCA7 (peak AMD SNP rs3752228, MAF=0.054 OR=1.22, p=0.00012). Next, we evaluated association of AMD with genes in ADrelated pathways identified by canonical pathway analysis of AD-associated genes. Significant associations were observed with multiple previously identified AMD risk loci and two novel genes: HGS (peak SNP rs8070488, MAF=0.23, OR=0.91, p=7.52×10−5), which plays a role in the © 2013 Elsevier Inc. All rights reserved. *Corresponding Author: Dr. Lindsay A. Farrer, Boston University School of Medicine, Biomedical Genetics L320, 72 East Concord Street, Boston, MA 02118, Tel: (617) 638-5393, Fax: (617) 638-4275, farrer@bu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflict of interest statement The authors have no conflict of interest to report. Data: These analyses have not been published elsewhere. This manuscript is not under consideration elsewhere. Human Subjects The present investigation occurred with appropriate IRB oversight and human subject protections. Author Statements All authors have reviewed the manuscript and have approved of its contents and validate the accuracy of the data. NIH Public Access Author Manuscript Neurobiol Aging. Author manuscript; available in PMC 2015 June 01. Published in final edited form as: Neurobiol Aging. 2014 June ; 35(6): 1510.e7–1510.e18. doi:10.1016/j.neurobiolaging. 2013.12. 007. N IH PA Athor M anscript N IH PA Athor M anscript N IH PA Athor M anscript clathrin-mediated endocytosis signaling pathway, and TNF (peak SNP rs2071590, MAF=0.34, OR=0.89, p=1.17×10−5), which is a member of the atherosclerosis signaling and the LXR/RXR activation pathways. Our results suggest that AMD and AD share genetic mechanisms.
A theory of graph comprehension.

Venn diagrams, flow charts, tree structures, node networks, to name just a few-or to the great lengths that computer companies go to advertise the graphic capabilities of their products, to see that charts and graphs have enormous appeal to people. All of this is true despite the fact that in virtually every case, the same information can be communicated by nonpictorial means: tables of numbers, lists of propositions cross-referI ! enced by global variables, labeled bracketings, and so on. Perhaps pictorial displays are simply pleasing to the eye, but both introspection and experimental evidence (Carter, 1947; Culbertson & Powers, 1959; Schutz, l%la, I
A Proteomic Study of HUPO’s Plasma Proteome Project Pilot Samples using an Accurate Mass and Time Tag Strategy

Characterization of the human blood plasma proteome is critical to the discovery of routinely useful clinical biomarkers. We used an Accurate Mass and Time (AMT) tag strategy with high-resolution mass accuracy capillary liquid chromatography Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry (cLC-FTICR MS) to perform a global proteomic analysis of pilot study samples as part of the HUPO Plasma Proteome Project. HUPO reference serum and citrated plasma samples from African Americans, Asian Americans, and Caucasian Americans were analyzed, in addition to a Pacific Northwest National Laboratory reference serum and plasma. The AMT tag strategy allowed us to leverage two previously published “shotgun” proteomics experiments to perform global analyses on these samples in triplicate in less than 4 days total analysis time. A total of 722 (22% with multiple peptide identifications) International Protein Index (IPI) redundant proteins, or 377 protein families by ProteinProphet, were identified over the 6 individual HUPO serum and plasma samples. The samples yielded a similar number of identified redundant proteins in the plasma samples (average 446 +/−23) as found in the serum samples (average 440+/−20). These proteins were identified by an average of 956+/−35 unique peptides in plasma and 930+/−11 unique peptides in serum. In addition to this high-throughput analysis, the AMT tag approach was used with a Z-score normalization to compare relative protein abundances. This analysis highlighted both known differences in serum and citrated plasma such as fibrinogens, and reproducible differences in peptide abundances from proteins such as soluble activin receptor-like kinase 7b and glycoprotein m6b. The AMT tag strategy not only improved our sample throughput, and provided a basis for estimated quantitation.
Preliminary studies with some hypotensive drugs

M); and for leptazol approximately 1.5 x 1O-3M. While " circuiting" was never seen with strychnine, a brief episode of uncoordinated violent activity was a characteristic effect of this drug, and was used as the strychnine endpoint EC50 (approximately 2.5 x 10-6M). Cunaniol was the most potent of these compounds, and it was also the most rapid in its onset of action. Only cunaniol acetate, with an EC50 of 4.5 x 10-7M (4.2-4.8 x 10-7M) was potent, and acted with similar rapidity to cunaniol.
Enhancing Hydrogen Production from Chlorella sp. Biomass by Pre-Hydrolysis with Simultaneous Saccharification and Fermentation (PSSF)

Simultaneous saccharification and fermentation (SSF) and pre-hydrolysis with SSF (PSSF) were used to produce hydrogen from the biomass of Chlorella sp. SSF was conducted using an enzyme mixture consisting of 80 filter paper unit (FPU) g-biomass−1 of cellulase, 92 U g-biomass−1 of amylase, and 120 U g-biomass−1 of glucoamylase at 35 °C for 108 h. This yielded 170 mL-H2 g-volatile-solids−1 (VS), with a productivity of 1.6 mL-H2 g-VS−1 h−1. Pre-hydrolyzing the biomass at 50 °C for 12 h resulted in the production of 1.8 g/L of reducing sugars, leading to a hydrogen yield (HY) of 172 mL-H2 g-VS−1. Using PSSF, the fermentation time was shortened by 36 h in which a productivity of 2.4 mL-H2 g-VS−1 h−1 was attained. To the best of our knowledge, the present study is the first report on the use of SSF and PSSF for hydrogen production from microalgal biomass, and the HY obtained in the study is by far the highest yield reported. Our results indicate that PSSF is a promising process for hydrogen production from microalgal biomass.
Transmembrane-truncated αvβ3 integrin retains high affinity for ligand binding : evidence for an ‘ inside-out ’ suppressor?

The molecular mechanisms of αvβ3 integrin affinity regulation have important biological implications in tumour development, wound repair and angiogenesis. We expressed, purified and characterized recombinant forms of human αvβ3 (r-αvβ3) and compared the activation state of these with αvβ3 in its cellular environment. The ligand specificity and selectivity of recombinant full-length and double transmembrane truncations of r-αvβ3 cloned in BacPAK6 vectors and expressed in Sf9 and High Five insect cells were compared with those of native placental αvβ3 and the receptor in situ on the cell surface. r-αvβ3 integrins were purified by affinity chromatography from detergent extracts of cells (full-length), and from the culture medium of cells expressing double-truncated r-αvβ3. r-αvβ3 had the same epitopes, ligandbinding specificities, bivalent cation requirements and suscep-
Quantication of microheterogeneity in glioblastoma multiforme with ex vivo high- resolution magic-angle spinning (HRMAS) proton magnetic resonance spectroscopy

logic characteristic in brain tumor pathology. Although microheterogeneity is readily documented by routine histologic techniques, these techniques only measure tumor status at the time of biopsy or surgery and do not indicate likely tumor progression. A biochemical screening technique calibrated against pathologic standards would greatly assist in predicting tumor progression from its biological activity. Here we demonstrate for the rst time that proton magnetic resonance spectroscopy (H MRS) with high-resolution magic-angle spinning (HRMAS), a technique introduced in 1997, can preserve tissue histopathologic features while producing well-resolved spectra of cellular metabolites in the identical intact tissue specimens. Observed biochemical alterations and tumor histopathologic characteristics can thus be correlated for the same surgical specimen, obviating the problems caused by tumor microheterogeneity. We analyzed multiple specimens of a single human glioblastoma multiforme surgically removed from a 44-year-old patient. Each specimen was rst measured with HRMAS H MRS to determine tumor metabolites, then evaluated by quantitative histopathology. The concentrations of lactate and mobile lipids measured with HRMAS linearly reected the percentage of tumor necrosis. Moreover, metabolic ratios of phosphorylcholine to choline correlated linearly with the percentage of the highly cellular malignant glioma. The quantication of tumor metabolic changes with HRMAS H MRS, in conjunction with subsequent histopathology of the same tumor specimen, has the potential to further our knowledge of the biochemistry of tumor heterogeneity during development, and thus ultimately to improve our accuracy in diagnosing, characterizing, and evaluating tumor progression. Neuro-Oncology 2, 87-95, 2000 (Posted to Neuro-Oncology [serial online], Doc. 99-44, March 22, 2000. URL <neuro-oncology.mc.duke.edu>)
Against Progressive Pneumonia Virus of Sheep

Various cell cultures were evaluated for their ability to support progressive pneumonia virus infection in vitro. Ovine trachea cells supported progressive pneumonia virus infection for an extended time, were extremely durable and could be passaged up until 30 passages. Progressive pneumonia virus infected ovine trachea cells were then used for the production of antigen for agar-gel immunodiffusion. A method for concentrating antigen, diafiltration, was compared to dialysis against polyethylene glycol. Using diafiltration, the concentrated virus was easily quantitated, less viscous (and therefore easier to apply) and only produced one precipitation line. Agar-gel immunodiffusion was used to survey 401 animals from two sheep flocks. One flock (96 sheep) was free of progressive pneumonia while the other flock had 111 of 305 total animals positive for precipitating antibodies. The incidence of precipitating antibodies in sheep ranged from 23% for yearling ewes to 80% in ewes seven years old.
Chronic ̄uoxetine treatment selectively uncouples raphe 5-HT1A receptors as measured by [S]-GTPgS autoradiography

1 Selective Serotonin Reuptake Inhibitors (SSRIs) are thought to have a delay in therapeutic ecacy because of the need to overcome the inhibitory in ̄uence of raphe 5-HT1A autoreceptors. Prolonged SSRI administration has been reported to desensitize these autoreceptors. We have used [S]-GTPgS autoradiography to determine whether this desensitization occurs at the level of receptor/G protein coupling. 2 Male mice were injected intraperitoneally once a day with saline or 20 mg kg ̄uoxetine for either 2 days or 14 days. 5-HT1A receptor binding and coupling to G proteins were assessed using [H]-8-OH-DPAT and [S]-GTPgS autoradiography, respectively. 3 The 5-HT receptor agonist 5-carboxamidotryptamine (5-CT) stimulated [S]-GTPgS binding in the substantia nigra, as well as in hippocampus and dorsal raphe nucleus. The 5-HT1A receptor antagonist p-MPPF (4̄uoro-N-(2-[4-(2-methoxyphenyl)1-piperazinyl]ethyl)-N-(2-pyridinyl)benzamide) blocked this eect in the latter regions, whereas the 5-HT1B/D antagonist GR-127,935 (2'methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yl)-biphenyl-4-carboxylic acid [4-methoxy-3-(4-methyl-piperazin-l-yl)-phenyl]-amide) only decreased labelling in substantia nigra. 4 Fourteen-day ̄uoxetine treatment decreased 5-CT-stimulated [S]-GTPgS binding in dorsal raphe (saline: 112+12% stimulation; ̄uoxetine: 66+13%), but not in substantia nigra (99+14% vs 103+7%) or hippocampus (157+3% vs 148+18%). Two-day ̄uoxetine treatment did not alter 5CT-stimulated [S]-GTPgS binding in any of the brain areas investigated. 5 Decreased [S]-GTPgS binding was not due to receptor down-regulation, since the density of raphe [H]-8-OH-DPAT binding sites was unaected by ̄uoxetine treatment. 6 These results suggest that the desensitization of presynaptic 5-HT1A receptor function occurs at the level of receptor-G protein interaction on dorsal raphe neurons, and may underlie the therapeutic ecacy of long-term SSRI treatment. British Journal of Pharmacology (2002) 135, 1115 ± 1122
Leukotriene B4 w-Hydroxylase in Human Polymorphonuclear Leukocytes

Human polymorphonuclear leukocytes (PMN) not only synthesize and respond to leukotriene B4 (LTB4), but also catabolize this mediator of inflammation rapidly and specifically by w-oxidation. To characterize the enzyme(s) responsible for w-oxidation of LTB4, human PMN were disrupted by sonication and subjected to differential centrifugation to yield membrane, granule, and cytosol fractions (identified by biochemical markers). LTB4 w-hydroxylase activity was concentrated (together with NADPH cytochrome c reductase activity) only in the membrane fraction (specific activity increased 10-fold as compared to whole sonicates, 41% recovery). Negligible activity was detected in granule or cytosol fractions. LTB4 w-hydroxylase activity in isolated PMN membranes was linear with respect to duration of incubation and protein concentration, was maximal at pH 7.4, had a K, for LTB4 of 0.6 MM, and was dependent on oxygen and on reduced pyridine nucleotides (apparent K. for NADPH = 0.5 AM; apparent K, for NADH = 223 MM). The LTB4 w-hydroxylase was inhibited significantly by carbon monoxide, ferricytochrome c, SKF-525A, and Triton X-100, but was not affected by a-naphthoflavone, azide, cyanide, catalase, and superoxide dismutase. Finally, isolated PMN membranes exhibited a carbon monoxide difference spectrum with a peak at 452 nm. Thus, we have partially purified the LTB. w-hydroxylase in human PMN and identified the enzyme as a membrane-associated, NADPHdependent cytochrome P450.
VERVET MONKEY DISEASE

BRIEF accounts (Smith, Simpson, Bowen and Zlotnik, 1967; Seigert, Shu, Hsiu-Lu, Slenczka, Peters and Muller, 1967) have described the isolation of the causative agent of a fatal human disease associated with handling blood and tissues from vervet monkeys (Cercopithecus aethiops). The growth of the agent in tissue culture has been described in detail (Zlotnik and Simpson, 1968; Zlotnik, Simpson, Bright, Bowen and Batter-Hatton, 1968). This paper describes the clinical, haematological and pathological findings in guinea-pigs and monkeys infected with the disease agent.
Effect of RecF protein on reactions

RecF protein is one of at least three single strand DNA (ssDNA) binding proteins which act in recombination and repair in Escherichia coli. In this paper we show that our RecF protein preparation complexes with ssDNA so as to retard its electrophoretic movement in an agarose gel. The apparent stoichiometry of RecFssDNA-binding measured in this way is one RecF molecule for every 15 nucleotides and the binding appears to be cooperative. Interaction of the other two ssDNA-binding proteins, RecA and Ssb proteins, has been studied extensively; so in this paper we begin the study of the interaction of RecF and RecA proteins. We found that the RecF protein preparation inhibits the activity of RecA protein in the formation of joint molecules whether added before or after addition of RecA protein to ssDNA. It, therefore, differs from Ssb protein which stimulates joint molecule formation when added to ssDNA after RecA protein. We found that our RecF protein preparation inhibits two steps prior to joint molecule formation: RecA protein binding to ssDNA and coaggregate formation between ssDNA-RecA complexes and dsDNA. We found that it required a much higher ratio of RecF to RecA protein than normally occurs in vivo to inhibit joint molecule formation. The insight that these data give to the normal functioning of RecF protein is discussed.
Allele-Specific Suppression of a Defective Brassinosteroid Receptor Reveals an Essential Role of UDP-Glucose: Glycoprotein Glucosyltransferase for High-Fidelity ER Quality Control

UDP-glucose:glycoprotein glucosyltransferase (UGGT) is a presumed folding sensor of protein quality control in the endoplasmic reticulum (ER). Previous biochemical studies with nonphysiological substrates revealed that UGGT can glucosylate nonnative glycoproteins by recognizing subtle folding defects, however, its physiological function remains undefined. Here we show that mutations in the Arabidopsis EBS1 gene suppressed the growth defects of a brassinosteroid (BR) receptor mutant, bri1-9, in an allele-specific manner by restoring its BR sensitivity. Using a mapbased cloning strategy, we discovered that EBS1 encodes the Arabidopsis homolog of UGGT. We demonstrated that bri1-9 is retained in the ER through interactions with several ER chaperones and that ebs1 mutations significantly reduce the stringency of the retention-based ER quality control, allowing export of the structurally-imperfect yet biochemically-competent bri1-9 to the cell surface for BR perception. Thus, our discovery provides the first genetic support for a physiological role of UGGT in high-fidelity ER quality control.
Infection with Blastomyces dermatitidis

V 1 J 1.1 /V 2 J 49 CD4 T Cells Mediate Resistance against Infection with Blastomyces dermatitidis Marcel Wüthrich,* Hanna I. Filutowicz, Holly L. Allen, George S. Deepe, and Bruce S. Klein Departments of Pediatrics, Internal Medicine, and Medical Microbiology and Immunology and Comprehensive Cancer Center, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, Wisconsin 53792, and Division of Infectious Diseases, University of Cincinnati College of Medicine and Veterans Affairs Hospital, Cincinnati, Ohio 45267
tRNA–guanine transglycosylase from Escherichia coli : Recognition of noncognate–cognate chimeric tRNA and discovery of a novel recognition site within the T CC arm of tRNA

tRNA–guanine transglycosylase (TGT) is a key enzyme involved in the posttranscriptional modification of tRNA across the three kingdoms of life. In eukaryotes and eubacteria, TGT is involved in the introduction of queuine into the anticodon of the cognate tRNAs. In archaebacteria, TGT is responsible for the introduction of archaeosine into the D-loop of the appropriate tRNAs. The tRNA recognition patterns for the eubacterial ( Escherichia coli ) TGT have been studied. These studies are all consistent with a restricted recognition motif involving a U-G-U sequence in a sevenbase loop at the end of a helix. While attempting to investigate the potential of negative recognition elements in noncognate tRNAs via the use of chimeric tRNAs, we have discovered a second recognition site for the E. coli TGT in the T CC arm of in vitro-transcribed yeast tRNA Phe. Kinetic analyses of synthetic mutant oligoribonucleotides corresponding to the T CC arm of the yeast tRNA Phe indicate that the specific site of TGT action is G53 (within a U-G-U sequence at the transition of the T CC stem into the loop). Posttranscriptional base modifications in tRNA Phe block recognition by TGT, most likely due to a stabilization of the tRNA structure such that G53 is inaccessible to TGT. These results demonstrate that TGT can recognize the U-G-U sequence within a structural context that is different than the canonical U-G-U in the anticodon loop of tRNA Asp . Although it is unclear if this second recognition site is physiologically relevant, this does suggest that other RNA species could serve as substrates for TGT in vivo.
Nevus-Count Data in Utah Kindreds

An analytic method is described for estimating phenotypic correlations between pairs of members of specific relationships in pedigrees. In estimating correlations, this new method allows simultaneous adjustment for available covariates such as age, gender, environmental factors, and variables reflecting ascertainment mode, through meanand variance-regression models. The estimated correlations and regression coefficients corresponding to covariates are consistent and asymptotically normally distributed. Differing from a fulllikelihood approach, this new method does not require the assumption of a particular joint distribution of phenotypes from a pedigree, such as the multivariate normal distribution, but instead only requires correct specification of meanand variance-regression models. Within this framework, missing data, if they are missing completely at random, can be ignored without biasing estimates. The method is illustrated by an application using nevus-count data from 28 Utah kinships. The results from the analysis are that covariateadjusted nevus counts are correlated between parents and children (correlation .22; P < .001) and between siblings (correlation .32; P < .001), while the correlation of . 04 between husband and wife is not significantly different (P = .31) from 0. This result is consistent with a genetic etiology of nevus count.