gebhart/patrepeval huggingface dataset:
Hepatitis B virus transactivator X protein is not tumorigenic in transgenic mice (1990)

The hepatitis B virus X protein acts as a transcriptional transactivator in vitro. To elucidate possible biological effects of X protein on liver cells in vivo, we generated four lines of transgenic mice carrying the X gene open reading frame under the control of the human alpha-1-antitrypsin regulatory region. The plasmid construct used to introduce the transgene was shown to encode a 16-kDa X protein with transactivating capability. The expression of X protein was detectable in liver tissue of transgenic animals of three of the lines by immunoblot analysis; levels of expression were highest in the first month after birth of the animals. Over 80 animals from the expressing lines were examined histologically. Most transgenic mice, some of which were observed for up to 2 years, remained normal. However, a few transgenic animals developed mild focal hepatitis, nuclear pleomorphism, focal necrosis, and/or nodular hyperplasia in the liver. Increased mitotic activity of hepatocytes also was observed. We conclude that, at the level of expression achieved in these transgenic mice, the hepatitis B virus transcriptional transactivator X protein alone does not appear to mediate the development of serious liver damage or hepatocellular carcinomas.
Regional left ventricular deafferentation increases baroreflex sensitivity following myocardial infarction (2003)

In animals with reduced BRS post-MI, deafferentation of the infarcted region prevented the progressive decline in sensitivity values that was noted in the control group. These data suggest that depressed BRS following MI is related to augmented afferent input from left ventricular receptors.
Independent association of uric acid levels with peripheral arterial disease in Taiwanese patients with Type 2 diabetes (2004)

Elevated uric acid level is a significant and independent risk factor for PAD in Taiwanese patients with Type 2 diabetes.
Complete amino acid sequence of human parathyroid hormone (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComplete amino acid sequence of human parathyroid hormoneHenry T. Keutmann, Mary M. Sauer, Geoff N. Hendy, Jeffrey L. H. O'Riordan, and John T. Potts, Jr.Cite this: Biochemistry 1978, 17, 26, 5723–5729Publication Date (Print):December 1, 1978Publication History Published online1 May 2002Published inissue 1 December 1978https://pubs.acs.org/doi/10.1021/bi00619a019https://doi.org/10.1021/bi00619a019research-articleACS PublicationsRequest reuse permissionsArticle Views258Altmetric-Citations100LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Promoter analysis of Helicobacter pylori genes with enhanced expression at low pH (2003)

To identify Helicobacter pylori genes with expression that is enhanced under low pH conditions, we used subtractive hybridization methodology. We identified 28 acid-induced genes, of which 18 have known or putative functions. Six pairs of genes were co-transcribed. Primer extension analysis identified single or multiple transcriptional start points (tsp) for 14 of the 22 loci. Sequence analysis of the -10 regions upstream of the tsps revealed consensus motifs for multiple RNA polymerase sigma factors present in H. pylori (sigma80, sigma54 and sigma28). No sequences resembling the -35 Escherichia coli consensus sequence (TTGACA) were present upstream of any of the genes. Both increased gene transcription and decreased mRNA decay contribute to the observed increase in H. pylori transcript abundance at acid pH. These studies document the complex response of H. pylori to environmental pH changes, and provide insight into mechanisms used for intragastric survival.
Theory and application of trapdoor functions (1982)

The purpose of this paper is to introduce a new information theory and explore its appplications. Using modern computational complexity, we study the notion of information that can be accessed through a feasible computation. In Part 1 of this paper, we lay the foundation of the theory and set up a framework for cryptography and pseudorandom number generation. In Part 2, we study the concept of trapdoor functions and examine applications of such functions in cryptography, pseudorandom number generation, and abstract complexity theory.
Rhythms ofDrosophila periodgene expression in culture (1997)

The Drosophila clock genes period (per) and timeless (tim) have been studied behaviorally and biochemically, but to date there has been no viable culture system for studying the cell biology of the Drosophila clock. We have cultured pupal ring glands attached to the central nervous system and observed rhythms of period gene expression in the prothoracic gland for 4-7 days. A daily rhythm of Per protein can be entrained by light in culture, even when neural activity is blocked by tetrodotoxin. In cultures maintained for a week in constant darkness, a per-luciferase reporter gene revealed circadian rhythms of bioluminescence. As the first circadian culture system from Drosophila, the prothoracic gland provides unique advantages for investigating the interactions between clock genes and cellular physiology.
CARCINOMA OF THE RECTUM AND OF THE RECTOSIGMOID IN THE YOUNG (1940)

The factors which influence the prognosis of carcinoma of the rectum and of the rectosigmoid in persons 30 years of age and less are multiple, although at present the most satisfactory indicators are the ability of the patient to withstand the effects of surgical removal of the lesion and the presence or absence of metastasis. The latter factor closely parallels the grade of the tumor as classified by Broders.<sup>1</sup>The clinical observations, the age and the sex of the patient and the rectal and proctoscopic observations, as well as the observations made at the time of surgical exploration, all must be correlated before the future health of a patient can be determined with any approximation of accuracy. The present paper is a review of 116 cases of carcinoma of the rectum and of the rectosigmoid in which persons 30 years of age and less were involved. The patients were
Synthesis and X-ray Crystal Structure of trans,cis-[Pt(OAc)2I2(en)]:  A Novel Type of Cisplatin Analog That Can Be Photolyzed by Visible Light to DNA-Binding and Cytotoxic Species in Vitro (1996)

An original approach intended to facilitate the intratumoral activation of Pt(IV) diamines by illumination with visible light to form photolysis products that irreversibly bind to DNA and are cytotoxic to human cancer cells is reported. The novel Pt(IV) complex trans,cis-[Pt(OAc)2I2(en)] was prepared by the acetylation of trans,cis-[Pt(OH)2I2(en)] with acetic anhydride in CH2Cl2; trans,cis-[Pt(OH)2I2(en)] was synthesized by oxidation of [PtI2(en)] with 30% aqueous H2O2. trans,cis-[Pt(OAc)2I2(en)] crystallized from methanol as deep-red needles with a = 9.029(4) Å, b = 11.443(2) Å, c = 12.822(2) Å, β = 95.48(3)°, monoclinic space group Cc, and Z = 4. The conformation of the acetato groups around the O−Pt−O axis deviated significantly from the conformation of the acetato groups in the X-ray crystal structure reported for the cis-dichloro analog, which may explain the very different aqueous solubilities of the two compounds. trans,cis-[Pt(OAc)2I2(en)] and trans,cis-[Pt(OH)2I2(en)] displayed broad ligand-to-metal charge-transfer bands centered at λ = 389 and 384 nm, respectively (ε = 1372 and 1425 M-1 cm-1, respectively), with tailing out to ca. 550 nm. When trans,cis-[Pt(OAc)2I2(en)] was incubated with calf thymus DNA in the absence of light, no covalent binding of Pt to DNA was measurable after 6 h; however, irradiation with light of wavelengths > 375 nm resulted in 63 ± 13% of the platinum being covalently bound to DNA after 6 h, suggesting that a photoreduction to Pt(II) species took place. Although trans,cis-[Pt(OH)2I2(en)] was also labile to visible light, only 10 ± 2% DNA platination was observed after 6 h of illumination; however, covalent binding of Pt to DNA took place quantitatively when a reducing agent such as glutathione was added to the photolyzed incubations. These results provide evidence that the photolysis of the trans-dihydroxo analog resulted predominately in the substitution of the iodide ligands for water rather than a reduction of Pt(IV) to Pt(II). When protected from light, trans,cis-[Pt(OAc)2I2(en)] and trans,cis-[Pt(OH)2I2(en)], both at a concentration of 10 μM, had half-lives of 6.6 ± 0.5 and 46.8 ± 8.8 h, respectively, at 37 °C in Eagle's minimum essential medium (EMEM) containing 5% fetal calf serum. When irradiated with light λirr > 375 nm, the half-lives were decreased by 24- and 53-fold for the diacetato- and dihydroxoplatinum(IV) complexes, respectively. Compared to the "dark" control, the in vitro treatment of TCCSUP human bladder cancer cells with trans,cis-[Pt(OAc)2I2(en)] resulted in 35% greater growth inhibitory activity when during the first 1.5 h of drug exposure the cells were irradiated with light λirr > 375 nm. The photolysis of trans,cis-[Pt(OH)2I2(en)] with visible light resulted in a 22% enhancement of antiproliferative activity.
Lysolecithin (1961)

Journal Article Lysolecithin Get access N Robinson N Robinson Department of Physical Chemistry, School of Pharmacy, University of London Brunswick Square, London, W.C. 1 Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 13, Issue 1, September 1961, Pages 321–354, https://doi.org/10.1111/j.2042-7158.1961.tb11831.x Published: 12 April 2011
Mycobacterium tuberculosiscontrols host innate immune activation through cyclopropane modification of a glycolipid effector molecule (2005)

Mycobacterium tuberculosis (Mtb) infection remains a global health crisis. Recent genetic evidence implicates specific cell envelope lipids in Mtb pathogenesis, but it is unclear whether these cell envelope compounds affect pathogenesis through a structural role in the cell wall or as pathogenesis effectors that interact directly with host cells. Here we show that cyclopropane modification of the Mtb cell envelope glycolipid trehalose dimycolate (TDM) is critical for Mtb growth during the first week of infection in mice. In addition, TDM modification by the cyclopropane synthase pcaA was both necessary and sufficient for proinflammatory activation of macrophages during early infection. Purified TDM isolated from a cyclopropane-deficient pcaA mutant was hypoinflammatory for macrophages and induced less severe granulomatous inflammation in mice, demonstrating that the fine structure of this glycolipid was critical to its proinflammatory activity. These results established the fine structure of lipids contained in the Mtb cell envelope as direct effectors of pathogenesis and identified temporal control of host immune activation through cyclopropane modification of TDM as a critical pathogenic strategy of Mtb.
Synthesis of very-long-chain bifunctional and isotope-labeled compounds for biochemical investigations into novel compounds in plant cuticular waxes (2012)

Plant cuticles are the interface for plant-environment interactions, and the first barrier protecting plants from environmental stresses such as water loss and pathogens. Structurally, the cuticle consists of a hydrophobic polymer lattice, cutin, and cuticular waxes deposited inside and outside cutin. The major components of the cuticular waxes are aliphatics derived from very-long-chain (VLC) fatty acids, such as alkanes and aldehydes. Besides compounds with primary functionalities, some compounds with two or more functional groups have also been identified in cuticular waxes. However, only limited knowledge about them has been acquired so far. The current work was to identify novel 1,2- and 1,3-bifunctional wax compounds from various plant species, in order to expand our current understanding of their structure, biosynthesis and function in plant cuticles. Synthetic methods were first developed to produce various VLC 1,2- and 1,3-bifunctionalized standard compounds for current and future structure elucidation studies. Unknown compounds found in Cosmos bipinnatus petal wax were identified as alkane-1,2-diol monoacetates by GC-MS, with chain lengths ranging from C20 to C24. The ratio between the primary and the secondary monoacetates was quantified to be 3:5, as opposed to the thermodynamic equilibrium ratio of 7:3. Novel β-hydroxy acid methyl esters were also identified from Aloe arborescens leaf wax, with chain lengths ranging from C26 to C30. In addition, two NMR-based methods were established to study the stereoconfigurations of alkane-1,2-diols from C. bipinnatus petal wax, and the carbons bearing secondary hydroxyl functionality were determined to have predominately the R-configuration. Apart from the research on bifunctional compounds, synthetic methods to produce β-deuterium labeled VLC substrates were also established. The resulting C30 fatty acid methyl ester was double-labeled and can be used directly or indirectly as substrates in future biochemical assays. At last, the hypothetic substrate for the CER1 enzyme implicated in wax alkane biosynthesis, C30 aldehyde, was synthesized and used in in vivo assays with heterologously expressed protein.
The caspase-cleaved DAP5 protein supports internal ribosome entry site-mediated translation of death proteins (2002)

Apoptosis is characterized by a translation switch from cap-dependent to internal ribosome entry site (IRES)-mediated protein translation. During apoptosis, several members of the eukaryotic initiation factor (eIF)4G family are cleaved specifically by caspases. Here we investigated which of the caspase-cleaved eIF4G family members could support cap-independent translation through IRES elements that retain activity in the dying cell. We focused on two major fragments arising from the cleavage of eIF4GI and death-associated protein 5 (DAP5) proteins (eIF4GI M-FAG/p76 and DAP5/p86, respectively), because they are the only potential candidates to preserve the minimal scaffold function needed to mediate translation. Transfection-based experiments in cell cultures indicated that expression of DAP5/p86 in cells stimulated protein translation from the IRESs of c-Myc, Apaf-1, DAP5, and XIAP. In contrast, these IRESs were refractory to the ectopically expressed eIF4GI M-FAG/p76. Furthermore, our study provides in vivo evidence that the caspase-mediated removal of the C-terminal tail of DAP5/p97 relieves an inhibitory effect on the protein's ability to support cap-independent translation through the DAP5 IRES. Altogether, the data suggest that DAP5 is a caspase-activated translation factor that mediates translation through a repertoire of IRES elements, supporting the translation of apoptosis-related proteins.
The Hepatitis B Virus Ribonuclease H Is Sensitive to Inhibitors of the Human Immunodeficiency Virus Ribonuclease H and Integrase Enzymes (2013)

Nucleos(t)ide analog therapy blocks DNA synthesis by the hepatitis B virus (HBV) reverse transcriptase and can control the infection, but treatment is life-long and has high costs and unpredictable long-term side effects. The profound suppression of HBV by the nucleos(t)ide analogs and their ability to cure some patients indicates that they can push HBV to the brink of extinction. Consequently, more patients could be cured by suppressing HBV replication further using a new drug in combination with the nucleos(t)ide analogs. The HBV ribonuclease H (RNAseH) is a logical drug target because it is the second of only two viral enzymes that are essential for viral replication, but it has not been exploited, primarily because it is very difficult to produce active enzyme. To address this difficulty, we expressed HBV genotype D and H RNAseHs in E. coli and enriched the enzymes by nickel-affinity chromatography. HBV RNAseH activity in the enriched lysates was characterized in preparation for drug screening. Twenty-one candidate HBV RNAseH inhibitors were identified using chemical structure-activity analyses based on inhibitors of the HIV RNAseH and integrase. Twelve anti-RNAseH and anti-integrase compounds inhibited the HBV RNAseH at 10 µM, the best compounds had low micromolar IC(50) values against the RNAseH, and one compound inhibited HBV replication in tissue culture at 10 µM. Recombinant HBV genotype D RNAseH was more sensitive to inhibition than genotype H. This study demonstrates that recombinant HBV RNAseH suitable for low-throughput antiviral drug screening has been produced. The high percentage of compounds developed against the HIV RNAseH and integrase that were active against the HBV RNAseH indicates that the extensive drug design efforts against these HIV enzymes can guide anti-HBV RNAseH drug discovery. Finally, differential inhibition of HBV genotype D and H RNAseHs indicates that viral genetic variability will be a factor during drug development.
Suicide Polymerase Endonuclease Restriction, a Novel Technique for Enhancing PCR Amplification of Minor DNA Templates (2005)

PCR-based molecular analyses can be hindered by the presence of unwanted or dominant DNA templates that reduce or eliminate detection of alternate templates. We describe here a reaction in which such templates can be exclusively digested by endonuclease restriction, leaving all other DNAs unmodified. After such a modification, the digested template is no longer available for PCR amplification, while nontarget DNAs remain intact and can be amplified. We demonstrate the application of this method and use denaturing gradient gel electrophoresis to ascertain the removal of target DNA templates and the subsequent enhanced amplification of nondigested DNAs. Specifically, plastid 16S rRNA genes were exclusively digested from environmental DNA extracted from plant roots. In addition, pure culture and environmental DNA extracts were spiked with various amounts of genomic DNA extracted from Streptomyces spp., and selective restriction of the Streptomyces 16S rRNA genes via the suicide polymerase endonuclease restriction PCR method was employed to remove the amended DNA.
Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations (2015)

Phenylketonuria (PKU) is an inborn error of phenylalanine (Phe) metabolism caused by the deficiency of phenylalanine hydroxylase. This deficiency leads to the accumulation of Phe and its metabolites in tissues and body fluids of PKU patients. The main signs and symptoms are found in the brain but the pathophysiology of this disease is not well understood. In this context, metabolic alterations such as oxidative stress, mitochondrial dysfunction, and impaired protein and neurotransmitters synthesis have been described both in animal models and patients. This review aims to discuss the main metabolic disturbances reported in PKU and relate them with the pathophysiology of this disease. The elucidation of the pathophysiology of brain damage found in PKU patients will help to develop better therapeutic strategies to improve quality of life of patients affected by this condition.
Antidepressant efficacy and tolerability of the selective norepinephrine reuptake inhibitor reboxetine: a review. (1998)

Reboxetine is a unique selective norepinephrine reuptake inhibitor (NRI) with proven antidepressant efficacy in pharmacologic and biochemical tests predictive of antidepressant properties. Comprehensive clinical trials, including 8 placebo-controlled and/or active treatment-controlled studies, plus 4 open studies, have assessed the short-term and long-term efficacy and tolerability of reboxetine in patients with major depressive disorders and dysthymia. Results from a total of 690 patients who entered 5 open or placebo-controlled studies are summarized in this paper. Four hundred forty-nine patients with a diagnosis of either major depressive disorder or dysthymia were treated with reboxetine in these clinical studies of 4 weeks' to 12 months' duration. In a 6-week placebo-controlled study, clinically significant improvement (> or = 50% reduction in Hamilton Rating Scale for Depression total score) was observed at last assessment in 74% of reboxetine-treated patients compared with 20% of patients in the placebo group. Similar results were observed in the 6-week run-in phases of the 3 long-term studies, where the efficacy of reboxetine was maintained over the 12-month study period. Reboxetine was well tolerated; adverse events reported were mainly mild to moderate in severity, and there were no clinically significant changes in vital signs or laboratory parameters. The first in its class, reboxetine, a selective NRI, will provide a valuable addition to the existing armamentarium of agents used in the treatment of depression.
Carotenoids up-regulate connexin43 gene expression independent of their provitamin A or antioxidant properties. (1992)

Epidemiological evidence and studies in whole animals and cell culture have indicated that carotenoids have cancer chemopreventive action. In mouse C3H10T1/2 cells, this activity is highly correlated with the ability of carotenoids to up-regulate gap junctional intercellular communication. Here, we report that in mouse cells, carotenoids increase the expression of connexin43, a gene that encodes a major gap junction protein. This effect appears unrelated to their provitamin A or antioxidant properties, since carotenoids with and without provitamin A activity increased levels of connexin43 mRNA and protein, whereas the antioxidants methyl-bixin and alpha-tocopherol were inactive. Moreover, the active carotenoid canthaxanthin did not induce the vitamin A-inducible gene retinoic acid receptor-beta. Connexin43 is the first carotenoid-inducible gene described in mammals. By indicating an additional pathway through which carotenoids function, these data provide a mechanistic basis for cancer chemoprevention by carotenoids and may lead to a re-evaluation of carotenoid physiology.