gebhart/patrepeval huggingface dataset:
A DNAzyme That Walks Processively and Autonomously along a One‐Dimensional Track (2005)

Inching its way forward: A DNA nanodevice is presented which can autonomously and processively move on a well-defined track with a 7-nm step size. The moving principle integrates DNAzyme activity and a strand-displacement strategy, which resembles the behavior of a caterpillar eating its way through a row of plants (see picture). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z500703_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity (2008)

Aminoglycoside ototoxicity has been related to a surprisingly large number of cellular structures and metabolic pathways. The finding that patients with mutations in mitochondrial rRNA are hypersusceptible to aminoglycoside-induced hearing loss has indicated a possible role for mitochondrial protein synthesis. To study the molecular interaction of aminoglycosides with eukaryotic ribosomes, we made use of the observation that the drug binding site is a distinct domain defined by the small subunit rRNA, and investigated drug susceptibility of bacterial hybrid ribosomes carrying various alleles of the eukaryotic decoding site. Compared to hybrid ribosomes with the A site of human cytosolic ribosomes, susceptibility of mitochondrial hybrid ribosomes to various aminoglycosides correlated with the relative cochleotoxicity of these drugs. Sequence alterations that correspond to the mitochondrial deafness mutations A1555G and C1494T increased drug-binding and rendered the ribosomal decoding site hypersusceptible to aminoglycoside-induced mistranslation and inhibition of protein synthesis. Our results provide experimental support for aminoglycoside-induced dysfunction of the mitochondrial ribosome. We propose a pathogenic mechanism in which interference of aminoglycosides with mitochondrial protein synthesis exacerbates the drugs' cochlear toxicity, playing a key role in sporadic dose-dependent and genetically inherited, aminoglycoside-induced deafness.
Beta-centractin: characterization and distribution of a new member of the centractin family of actin-related proteins. (1994)

An examination of human-expressed sequence tags indicated the existence of an isoform of centractin, an actin-related protein localized to microtubule-associated structures. Using one of these tags, we isolated and determined the nucleotide sequence of a full-length cDNA clone. The protein encoded represents the first example of multiple isoforms of an actin-related protein in a single organism. Northern analysis using centractin-specific probes revealed three species of mRNA in HeLa cells that could encode centractin isoforms. One mRNA encodes the previously-identified centractin (now referred to as alpha-centractin). The full-length cDNA clone isolated using the expressed sequence tag encodes a new member of the centractin family, beta-centractin. A probe specific for alpha-centractin hybridized to the third species of mRNA observed (referred to as gamma-centractin). Comparisons of Northern blots of human tissues indicated that alpha-centractin and beta-centractin mRNAs are equally distributed in all populations of mRNA examined, whereas the expression of gamma-centractin appears to be tissue specific. The amino acid sequence of beta-centractin, deduced from the cDNA, indicates a 91% identity with alpha-centractin, increasing to 96% similarity when conservative amino acid changes are taken into account. As antibodies previously raised against alpha-centractin reacted only poorly with beta-centractin, new antibodies were produced and combined with two-dimensional gel electrophoresis to discriminate the two isoforms. Using this system, the subcellular distribution of the alpha- and beta-isoforms were determined. Both isoforms were found predominantly in the cytosolic fraction as a part of a previously identified 20S complex (referred to as the dynactin complex) with no evidence for a free pool of either isoform. The isoforms were found in a constant ratio of approximately 15:1 (alpha:beta) in the dynactin complex.
Evaluation of the 40 mg Swelling Test for Measuring Starch Functionality (2001)

This paper presents a small-scale test for measuring starch quality and demonstrates its ability to predict end-product quality. This 40 mg swelling test measures the swelling power of gelatinised starch by determining the mass of the final product after a defined gelatinisation process. It is compared with the larger scale swelling power and swelling volume tests and with other starch gel analyses methods (differential scanning calorimetry, hot stage microscopy and Rapid Visco Analyser). Suitability of the 40 mg swelling test as a small-scale early generation breeding test for measuring starch quality is evaluated. This new method is also evaluated as being suitable to provide an indication of the end-product quality of Japanese white salted noodles.
Rotavirus and hemolytic enteropathogenic Escherichia coli in weanling diarrhea of pigs (1982)

Since the turn of the century, Escherichia coli has been implicated in the etiology of weanling diarrhea (colibacillosis). However, rotavirus--a virus that destroys enterocytes--has been shown recently to be causally associated with weanling diarrhea of pigs. The role of both rotavirus and hemolytic enteropathogenic E. coli in weanling diarrhea was assessed in this study. Pigs from a closed herd were farrowed and weaned by two markedly different systems: an "intensive care sanitary" system and a "conventional unsanitary" system. Pigs weaned at 3 weeks of age in the sanitary system usually experienced a rotaviral diarrhea about 16 days postweaning. No hemolytic E. coli were detected in feces from these pigs. Peers weaned at the same time by the unsanitary system commenced diarrhea 3 days postweaning. Rotavirus and nonhemolytic E. coli were detected in the feces at the onset of diarrhea and for a few days thereafter. Then, the aerobic fecal flora shifted to nearly pure hemolytic enteropathogenic E. coli. About 10 days later, the diarrhea waned, and the fecal flora shifted back to nonhemolytic E. coli. This hemolytic E. coli shedding pattern could not be duplicated in artificially inoculated sanitary pigs unless they were inoculated with the hemolytic E. coli during a rotaviral-associated diarrhea. Otherwise, the shedding of hemolytic E. coli was fleeting, and the diarrhea, if present, was mild. Pigs developed humoral antibodies to the rotavirus but not to the hemolytic E. coli. We conclude that rotavirus damages the epithelium of the small intestines, which changes the luminal environment to one that favors colonization by enteropathogenic E. coli.
Total Synthesis as a Resource in the Discovery of Potentially Valuable Antitumor Agents: Cycloproparadicicol (2003)

A highly convergent synthesis was used to prepare a series of epimers and analogues of radicicol (1). Biological assessment revealed a previously unrecognized correlation between stereochemistry and antitumor potential in these compounds. Significantly, cycloproparadicicol (2) showed promising therapeutic properties based on inhibition of chaperones.
Preliminary investigations of an amperometric oligosaccharide dehydrogenase-based electrode for the detection of glucose and some other low molecular weight saccharides (1996)

Biosensors for the determination of sugars were constructed using oligosaccharide dehydrogenase (ODH) and soluble phenazine methosulfate (PMS) or an osmium-based three-dimensional redox hydrogel. In the latter case the enzyme and poly(1-vinylimidazole) complexed with osmium (4,4'-dimethylbpy)2Cl were cross-linked with poly(ethylene glycol) diglycidyl ether. Both electrode configurations showed similar sensitivities for glucose in the range between 8 and 21 muAmM-1 cm-2. The responses for 10 mono and oligosaccharides were studied. There was no response for fructose. In the concentration range 0.1-20 mM the relative sensitivities were determined for arabinose (96%), xylose (3%), mannose (50%), galactose (11%), glucose (100%), maltose (24%), lactose (12%), cellobiose (34%) and maltotriose (10%).
NS-7 (Nippon Shinyaku). (2000)

Nippon Shinyaku is developing NS-7, a sodium and calcium channel blocker, as a neuroprotectant for use following cerebral infarction [249336]. It entered phase I trials for the treatment of acute stage cerebrovascular disorders in 1997 [271963]. As of November 1999, Nippon Shinyaku was preparing to start phase II studies in Japan [347972]. In November 1999, Nippon Shinyaku granted Schering exclusive developing and marketing rights to NS-7. Schering will conduct clinical trials in Europe and the US [347972].
In vitro synthesis of molybdopterin from precursor Z using purified converting factor. Role of protein-bound sulfur in formation of the dithiolene (1993)

The pterin component of the molybdenum cofactor, termed molybdopterin, is synthesized in Escherichia coli by enzymes encoded at the chl loci. A late step in the biosynthetic pathway, the conversion of a molybdopterin intermediate, precursor Z, to molybdopterin, requires the activity of a two-subunit protein, the converting factor. Precursor Z has many of the features of molybdopterin but lacks the dithiolene function essential for molybdenum ligation. Conversion of precursor Z to molybdopterin is accomplished by transfer of sulfur to produce the dithiolene. The present study describes an in vitro system for molybdopterin biosynthesis comprised of purified precursor Z and purified converting factor. It is established that these components are sufficient to yield molybdopterin, identified by conversion to its characteristic products, Form A, Form B, and dicarboxamidomethylmolybdopterin. Under conditions of precursor excess, the formation of molybdopterin was stoichiometric with converting factor, as would be expected in the absence of a sulfur-regenerating system. The labile product of the reaction, molybdopterin, remained associated with the converting factor large subunit. These results establish that the source of sulfur for molybdopterin biosynthesis is the converting factor and suggest that in vivo a novel sulfur cycle must function to resupply sulfur to the converting factor.
Pim‐1 expression in prostatic intraepithelial neoplasia and human prostate cancer (2004)

Our data suggest that PIM-1 overexpression in HGPIN may be an early event in the development of prostate malignancy. Additionally, PIM-1 expression provides supplementary information for distinguishing HGPIN from benign epithelium.
Challenges and Opportunities in the Discovery of New Therapeutics Targeting the Kynurenine Pathway (2015)

The kynurenine pathway is responsible for the metabolism of more than 95% of dietary tryptophan (TRP) and produces numerous bioactive metabolites. Recent studies have focused on three enzymes in this pathway: indoleamine dioxygenase (IDO1), kynurenine monooxygenase (KMO), and kynurenine aminotransferase II (KAT II). IDO1 inhibitors are currently in clinical trials for the treatment of cancer, and these agents may also have therapeutic utility in neurological disorders, including multiple sclerosis. KMO inhibitors are being investigated as potential treatments for neurodegenerative diseases, such as Huntington's and Alzheimer's diseases. KAT II inhibitors have been proposed in new therapeutic approaches toward psychiatric and cognitive disorders, including cognitive impairment associated with schizophrenia. Numerous medicinal chemistry studies are currently aimed at the design of novel, potent, and selective inhibitors for each of these enzymes. The emerging opportunities and significant challenges associated with pharmacological modulation of these enzymes will be explored in this review.
The biological clock tunes the organs of the body: timing by hormones and the autonomic nervous system (2003)

The biological clock, the suprachiasmatic nucleus (SCN), is essential for our daily well-being. It prepares us for the upcoming period of activity by an anticipatory rise in heart rate, glucose and cortisol. At the same time the 'hormone of the darkness', melatonin, decreases. Thus, the time-of-day message penetrates into all tissues, interestingly not only by means of hormones but also by a direct neuronal influence of the SCN on the organs of the body. The axis between the SCN and the paraventricular nucleus of the hypothalamus (PVN) is crucial for the organization/synchronization of the neuroendocrine and autonomic nervous system with the time of day. This SCN-neuroendocrine PVN axis takes care of a timely hormonal secretion. At the same time, the SCN-autonomic PVN axis fine-tunes the organs by means of the autonomic nervous system for the reception of these hormones. Finally, the similar organization of the projections of the human SCN as compared with that in the rodent brain suggests that these basic principles of neuroendocrine autonomic interaction may also be true in the human. The physiological data collected in humans thus far seem to support this hypothesis, while pathological changes in the SCN of humans suffering from depression or hypertension indicate a role for the SCN in the etiology of these diseases.
Possible applications of scanning frequency comb microscopy for carrier profiling in semiconductors (2014)

In scanning frequency comb microscopy, a mode-locked ultrafast laser is focused on the tunneling junction of a scanning tunneling microscope to generate a microwave frequency comb (MFC) with hundreds of measurable harmonics that is superimposed on the dc tunneling current when the sample is metallic. With semiconductor samples, each laser pulse creates a surface charge that may have a radius of less than 1 nm, and this charge is rapidly dispersed by intense electrostatic repulsion. Time or frequency-domain measurements of the resulting pulse train with semiconductors, or hyperspectral measurements of the MFC with metals, may be used to determine the properties near the surface of a sample with atomic resolution.
Factor Xa Inhibitors: Next-Generation Antithrombotic Agents (2010)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTFactor Xa Inhibitors: Next-Generation Antithrombotic AgentsDonald J. P. Pinto, Joanne M. Smallheer, Daniel L. Cheney, Robert M. Knabb, and Ruth R. Wexler*View Author Information Research and Development, Bristol-Myers Squibb Company, P.O. Box 5400, Princeton, New Jersey, 08543*To whom correspondence should be addressed. Phone: (609) 818-5450. Fax: (609) 818-3331. E-mail: [email protected]Cite this: J. Med. Chem. 2010, 53, 17, 6243–6274Publication Date (Web):May 26, 2010Publication History Received3 February 2010Published online26 May 2010Published inissue 9 September 2010https://pubs.acs.org/doi/10.1021/jm100146hhttps://doi.org/10.1021/jm100146hreview-articleACS PublicationsCopyright © 2010 American Chemical SocietyRequest reuse permissionsArticle Views6420Altmetric-Citations115LEARN 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 SUBJECTS:Bioavailability,Inhibitors,Monomers,Peptides and proteins,Rodent models Get e-Alerts
Mycobacteria contain two groEL genes: the second Mycobacterium leprae groEL gene is arranged in an operon with groES (1992)

In contrast to other bacterial species, mycobacteria were thus far considered to contain groEL and groES genes that are present on separate loci on their chromosomes, Here, by screening a Mycobacterium leprae lambda gt11 expression library with serum from an Ethiopian lepromatous leprosy patient, two DNA clones were isolated that contain a groEL gene arranged in an operon with a groES gene. The complete DNA sequence of this groESL operon was determined. The predicted amino acid sequences of the GroES and GroEL proteins encoded by this operon are 85-90% and 59-61% homologous to the sequences from previously characterized mycobacterial GroES and GroEL proteins. Southern blotting analyses with M. leprae groES- and groEL-specific probes demonstrate that similar groESL homologous DNA is present in the genomes of other mycobacteria, including Mycobacterium tuberculosis. This strongly suggests that mycobacteria contain a groESL operon in addition to a separately arranged second groEL gene. Using five T-cell clones from two leprosy patients as probes, expression of the M. leprae GroES protein in Escherichia coli after heat shock was demonstrated. Four of these clones recognized the same M. leprae-specific GroES-derived peptide in a DR2-restricted fashion. No expression of the groEL gene from this operon was detected in E. coli after heat shock, as tested with a panel of T-cell clones and monoclonal antibodies reactive to previously described GroEL proteins of mycobacteria.
The 2.0 Å crystal structure of the ERα ligand‐binding domain complexed with lasofoxifene (2007)

Lasofoxifene is a new and potent selective estrogen receptor modulator (SERM). The structural basis of its interaction with the estrogen receptor has been investigated by crystallographic analysis of its complex with the ligand-binding domain of estrogen receptor alpha at a resolution of 2.0 A. As with other SERMs, lasofoxifene diverts the receptor from its agonist-bound conformation by displacing the C-terminal AF-2 helix into the site at which the LXXLL motif of coactivator proteins would otherwise be able to bind. Lasofoxifene achieves this effect by occupying the space normally filled by residue Leu 540, as well as by modulating the conformation of residues of helix 11 (His 524, Leu 525). A well-defined salt bridge between lasofoxifene and Asp 351 suggests that charge neutralization in this region of the receptor may explain the some of the antiestrogenic effects of lasofoxifene. The results suggest general features of ERalpha/SERM recognition, and add a new dimension to efforts to rationalize differences between the biological activity profiles exhibited by these important pharmacological agents.
ChemInform Abstract: Structure‐Activity Relationship of Quinazolinedione Inhibitors of Calcium‐Independent Phosphodiesterase. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Human endothelial colony-forming cells serve as trophic mediators for mesenchymal stem cell engraftment via paracrine signaling (2014)

Endothelial colony-forming cells (ECFCs) are endothelial precursors that circulate in peripheral blood. Studies have demonstrated that human ECFCs have robust vasculogenic properties. However, whether ECFCs can exert trophic functions in support of specific stem cells in vivo remains largely unknown. Here, we sought to determine whether human ECFCs can function as paracrine mediators before the establishment of blood perfusion. We used two xenograft models of human mesenchymal stem cell (MSC) transplantation and studied how the presence of ECFCs modulates MSC engraftment and regenerative capacity in vivo. Human MSCs were isolated from white adipose tissue and bone marrow aspirates and were s.c. implanted into immunodeficient mice in the presence or absence of cord blood-derived ECFCs. MSC engraftment was regulated by ECFC-derived paracrine factors via platelet-derived growth factor BB (PDGF-BB)/platelet-derived growth factor receptor (PDGFR)-β signaling. Cotransplanting ECFCs significantly enhanced MSC engraftment by reducing early apoptosis and preserving stemness-related properties of PDGFR-β(+) MSCs, including the ability to repopulate secondary grafts. MSC engraftment was negligible in the absence of ECFCs and completely impaired in the presence of Tyrphostin AG1296, an inhibitor of PDGFR kinase. Additionally, transplanted MSCs displayed fate-restricted potential in vivo, with adipose tissue-derived and bone marrow-derived MSCs contributing exclusive differentiation along adipogenic and osteogenic lineages, respectively. This work demonstrates that blood-derived ECFCs can serve as paracrine mediators and regulate the regenerative potential of MSCs via PDGF-BB/PDGFR-β signaling. Our data suggest the systematic use of ECFCs as a means to improve MSC transplantation.
Design of strip-loaded weak-guiding multimode interference structure for an optical router (1998)

We introduce a new multimode interference structure that can be used as an integrated optical router. This structure is based on the existence of a first cross state in weakly guiding multimode waveguides. Such a cross image, not expected by the self-imaging technique, is tested by rigorous modal analysis as well as the nonmodal beam propagation method. We show that the quality of this image could be enhanced by strip loading the multimode section of the structure. Making use of this image, we propose a new optical router based on the large nonlinearity associated with the blockaded reservoir and quantum-well electron transfer structure.
Mechanisms for Interferon-α-Induced Depression and Neural Stem Cell Dysfunction (2014)

New neurons generated by the neural stem cells (NSCs) in the adult hippocampus play an important role in emotional regulation and respond to the action of antidepressants. Depression is a common and serious side effect of interferon-α (IFN-α), which limits its use as an antiviral and antitumor drug. However, the mechanism(s) underlying IFN-induced depression are largely unknown. Using a comprehensive battery of behavioral tests, we found that mice subjected to IFN-α treatment exhibited a depression-like phenotype. IFN-α directly suppressed NSC proliferation, resulting in the reduced generation of new neurons. Brain-specific mouse knockout of the IFN-α receptor prevented IFN-α-induced depressive behavioral phenotypes and the inhibition of neurogenesis, suggesting that IFN-α suppresses hippocampal neurogenesis and induces depression via its receptor in the brain. These findings provide insight for understanding the neuropathology underlying IFN-α-induced depression and for developing new strategies for the prevention and treatment of IFN-α-induced depressive effects.