gebhart/patrepeval huggingface dataset:
Novel Small Molecule Growth Inhibitor Affecting Bacterial Outer Membrane Reduces Extraintestinal Pathogenic Escherichia coli (ExPEC) Infection in Avian Model (2021)

Avian pathogenic Escherichia coli (APEC), a subgroup of extraintestinal pathogenic E. coli (ExPEC), causes colibacillosis in chickens and is reportedly implicated in urinary tract infections and meningitis in humans. A major limitation for the current ExPEC antibiotic therapy is the development of resistance, and antibacterial drugs that can circumvent this problem are critically needed. Here, we evaluated eight novel membrane-affecting anti-APEC small molecule growth inhibitors (GIs), identified in our previous study, against APEC infection in chickens. Among the GIs tested, GI-7 (the most effective), when administered orally (1 mg/kg of body weight), reduced the mortality (41.7%), severity of lesions (62.9%), and APEC load (2.6 log) in chickens. Furthermore, GI-7 administration at an optimized dose (60 mg/liter) in drinking water also reduced the mortality (14.7%), severity of lesions (29.5%), and APEC load (2.2 log) in chickens. The abundances of <i>Lactobacillus</i> and oleate were increased in the cecum and serum, respectively, of GI-7-treated chickens. Pharmacokinetic analysis revealed that GI-7 was readily absorbed with minimal accumulation in the tissues. Earlier, we showed that GI-7 induced membrane blebbing and increased membrane permeability in APEC, suggesting an effect on the APEC membrane. Consistent with this finding, the expression of genes essential for maintaining outer membrane (OM) integrity was downregulated in GI-7-treated APEC. Furthermore, decreased levels of lipopolysaccharide (LPS) transport (Lpt) proteins and LPS were observed in GI-7-treated APEC. However, the mechanism of action of GI-7 currently remains unknown and needs further investigation. Our studies suggest that GI-7 represents a promising novel lead compound that can be developed to treat APEC infection in chickens and related human ExPEC infections. <b>IMPORTANCE</b> APEC is a subgroup of ExPEC, and genetic similarities of APEC with human ExPECs, including uropathogenic E. coli (UPEC) and neonatal meningitis E. coli (NMEC), have been reported. Our study identified a novel small molecule growth inhibitor, GI-7, effective in reducing APEC infection in chickens with an efficacy similar to that of the currently used antibiotic sulfadimethoxine, notably with an 8-times-lower dose. GI-7 affects the OM integrity and decreases the Lpt protein and LPS levels in APEC, an antibacterial mechanism that can overcome the antibiotic resistance problem. Overall, GI-7 represents a promising lead molecule/scaffold for the development of novel antibacterial therapies that could have profound implications for treating APEC infections in chickens, as well as human infections caused by ExPECs and other related Gram-negative bacteria. Further elucidation of the mechanism of action of GI-7 and identification of its target(s) in APEC will benefit future novel antibacterial development efforts.
Polyene macrolide antibiotic amphotericin B. Crystal structure of the N-iodoacetyl derivative (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolyene macrolide antibiotic amphotericin B. Crystal structure of the N-iodoacetyl derivativePaolo Ganis, Gustavo Avitabile, Witold Mechlinski, and Carl P. SchaffnerCite this: J. Am. Chem. Soc. 1971, 93, 18, 4560–4564Publication Date (Print):September 1, 1971Publication History Published online1 May 2002Published inissue 1 September 1971https://pubs.acs.org/doi/10.1021/ja00747a037https://doi.org/10.1021/ja00747a037research-articleACS PublicationsRequest reuse permissionsArticle Views741Altmetric-Citations165LEARN 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
Effects of Local Corticosteroids in Skin Infections (1976)

Glucocorticoids exert valuable therapeutic activities in skin infections, although their use is limited by the occurrence of undesiderable effects: glucocorticoids depress the local defense mechanisms and in low concentrations, stimulate microbiol metabolism. For these reasons, combined preparations containing an antimicrobiol substance besides the glucocorticoid are recommended. However, interactions between the steroids and the antimicrobiols must be ruled out beforehand, i.e. the unimpaired activity of both steroid and antimicrobial must be assured. Examples of such investigations are reported for the most widely used compounds for topical therapy. The simultaneous use of a glucocorticoid and an antimicrobial is not recommended in only a few instances.
Light-weight alloys for aerospace applications; Proceedings of the Symposium, Las Vegas, NV, Feb. 28-Mar. 2, 1989 (1989)

Various papers on lightweight alloys for aerospace applications are presented. Individual topics addressed include: P/M-aluminum alloy for high-temperature application, elevated temperature behavior of RST Al-Ti-X alloys, microstructural characterization of rapidly solidified Al-Ze-V alloys, high-strength aluminum alloys for aerospace applications, oxidation behavior of some Mg-Li and Mg-Li-SI alloys, the effect of various environments on fatigue crack propagation in a 2090 Al-Li alloy, and surface-generated scratches and their effects on the fatigue life of Al-Li alloys. Consideration is given to the stretch formability of sheet Al-Li, hydrogen solution in Al-Li alloys, particle-reinforced aluminum-based composites, applications for discontinuously reinforced aluminum, age hardening of cast SiC-reinforced Mg-6Zn, superplasticity in high-strength aluminum alloys and in spray-deposited 7075 Al alloys, and superplastic behavior in an aluminum-lithium alloy.
Cellular Protein WDR11 Interacts with Specific Herpes Simplex Virus Proteins at the<i>trans</i>-Golgi Network To Promote Virus Replication (2015)

While the TGN has been proposed to be the major site of HSV-1 secondary envelopment, this process is incompletely understood, and in particular, the role of cellular TGN components in this pathway is unknown. Additionally, little is known about the cellular functions of WDR11, although the disruption of this protein has been implicated in multiple human diseases. Therefore, our finding that WDR11 is a TGN-resident protein that interacts with specific viral proteins to enhance viral yields improves both our understanding of basic cellular biology as well as how this protein is co-opted by HSV.
High-Throughput Sequencing of mGluR Signaling Pathway Genes Reveals Enrichment of Rare Variants in Autism (2012)

Identification of common molecular pathways affected by genetic variation in autism is important for understanding disease pathogenesis and devising effective therapies. Here, we test the hypothesis that rare genetic variation in the metabotropic glutamate-receptor (mGluR) signaling pathway contributes to autism susceptibility. Single-nucleotide variants in genes encoding components of the mGluR signaling pathway were identified by high-throughput multiplex sequencing of pooled samples from 290 non-syndromic autism cases and 300 ethnically matched controls on two independent next-generation platforms. This analysis revealed significant enrichment of rare functional variants in the mGluR pathway in autism cases. Higher burdens of rare, potentially deleterious variants were identified in autism cases for three pathway genes previously implicated in syndromic autism spectrum disorder, TSC1, TSC2, and SHANK3, suggesting that genetic variation in these genes also contributes to risk for non-syndromic autism. In addition, our analysis identified HOMER1, which encodes a postsynaptic density-localized scaffolding protein that interacts with Shank3 to regulate mGluR activity, as a novel autism-risk gene. Rare, potentially deleterious HOMER1 variants identified uniquely in the autism population affected functionally important protein regions or regulatory sequences and co-segregated closely with autism among children of affected families. We also identified rare ASD-associated coding variants predicted to have damaging effects on components of the Ras/MAPK cascade. Collectively, these findings suggest that altered signaling downstream of mGluRs contributes to the pathogenesis of non-syndromic autism.
Sandostatin LAR in Acromegalic Patients: Long Term Treatment (1997)

We have evaluated the long term effects and safety of Sandostatin LAR, a long acting formulation of octreotide, during 18 subsequent injections given every fourth week to 14 octreotide-sensitive acromegalic patients. The dosages (20, 30, or 40 mg) were adjusted according to GH response, side-effects, or symptom relief and assessed on day 28 after each injection. We found a stable and consistent suppression of GH and insulin-like growth factor (IGF-I) during the entire study period. Daily mean GH levels were suppressed below 2 micrograms/L in 9, to between 2-5 micrograms/L in 3, and to between 5-10 micrograms/L in 2 patients. The corresponding IGF-I values were suppressed to below 500 micrograms/L in 9 patients and to between 500-1000 micrograms/L in the remaining 5 patients. Increasing the dosage of Sandostatin LAR from 20 to 30 mg had no obvious additional effect on GH suppression, but provided a further decrease in IGF-I levels. Forty milligrams of the drug had no additional effect on GH or IGF-I compared to 30 mg. Acromegalic signs and symptoms improved during treatment. Although the fluctuations of daily mean octreotide levels were high, dosage increments caused an increase in the average serum concentration in the individual patient. Pituitary tumor size reduction was seen in all previously untreated patients (n = 4). We found only minor changes in glucose metabolism (oral glucose tolerance test and hemoglobin A1C) during treatment, but no biologically relevant changes in thyroid function (TSH, T3, and free T4). One patient developed asymptomatic gallstones, and another acquired vitamin B12 deficiency during treatment. The drug is well tolerated during long term treatment. Sandostatin LAR may well be the future medical treatment of choice for acromegalic patients.
The Icelandic Healthcare Database and Informed Consent (2000)

Modern information technology is rapidly changing how new knowledge is discovered in most fields of science, including medicine. This technology offers interesting possibilities in the development of methods to understand diseases better, but it also presents new ethical challenges. The new technology offers the possibility of mining large data sets for knowledge, without a priori hypotheses, by systematically juxtaposing various data in the search for the best fit. This kind of pure combinatorial analysis may be particularly powerful in the case of the common diseases, most of which are complex and have remained beyond the reach of the classic hypothesis-driven . . .
On the Association of Bacteria with Larvae and Galls of Anguina Tritici (1988)

External attachment of spores of Corynebacterium michiganensis pv. tritici with body surface of second stage larvae of Anguina tritici has been positively demonstrated. Beside C. michiganense pv. tritici, ten other bacterial flora were found to be present in the nematode galls. Of these, five species (Bacillus subtilis, B. pumilus, B. cereus and two other species of Pseudomonas) were found to be larvicidal.
Recognition of Escherichia coli valine transfer RNA by its cognate synthetase: a fluorine-19 NMR study (1991)

Interactions of 5-fluorouracil-substituted Escherichia coli tRNAVal with its cognate synthetase have been investigated by fluorine-19 nuclear magnetic resonance. Valyl-tRNA synthetase (VRS) (EC 6.1.1.9), purified to homogeneity from an overproducing strain of E. coli, differs somewhat from VRS previously isolated from E. coli K12. Its amino acid composition and N-terminal sequence agree well with results derived from the sequence of the VRS gene [Heck, J.D., & Hatfield, G.W. (1988) J. Biol. Chem. 263, 868-877]. Apparent KM and Vmax values of the purified VRS are the same for both normal and 5-fluorouracil (FUra)-substituted tRNAVal. Binding of VRS to (FUra)tRNAVal induces structural perturbations that are reflected in selective changes in the 19F NMR spectrum of the tRNA. Addition of increasing amounts of VRS results in a gradual loss of intensity at resonances corresponding to FU34, FU7, and FU67, with FU34, at the wobble position of the anticodon, being affected most. At higher VRS/tRNA ratios, a broadening and shifting of FU12 and of FU4 and/or FU8 occur. These results indicate that VRS interacts with tRNAVal along the entire inside of the L-shape molecule, from the acceptor stem to the anticodon. Valyl-tRNA synthetase also causes a splitting of resonances FU55 and FU64 in the T-loop and stem of tRNAVal, suggesting conformational changes in this part of the molecule. No 19F NMR evidence was found for formation of the Michael adduct between VRS and FU8 of 5-fluorouracil-substituted tRNAVal that has been proposed as a common intermediate in the aminoacylation reaction.
Multimerization of monocyte chemoattractant protein-1 is not required for glycosaminoglycan-dependent transendothelial chemotaxis (2001)

Chemokines interact with specific G-protein-coupled cell-surface receptors and with glycosaminoglycans (GAGs), such as heparan sulphate. Although chemokines often form multimers in solution, this process may be enhanced following interaction with GAGs on the cell surface, or within the extracellular matrix. However, the significance of multimerization for chemokine function remains controversial. In the present study, a fusion protein was prepared between the prototypical human CC chemokine, monocyte chemoattractant protein-1 (MCP-1; also known as CCL-2) and a large secreted placental alkaline phosphatase (SEAP) moiety. This fusion protein (MCP-1–SEAP) remained monomeric under conditions that promote oligomerization of the native chemokine. Radioligand binding showed that both native MCP-1 and MCP-1–SEAP competed for the same site on the surface of HEK-293 cells expressing the CCR2b chemokine receptor. The interaction between either chemokine species and endothelial cell surface GAGs was antagonized by the addition of the heparan sulphate-like molecule, heparin. Both MCP-1 and MCP-1–SEAP induced a Ca2+-flux in the THP-1 monocytic cell line, and were equally effective at promoting transendothelial chemotaxis of mononuclear immune cells, with maximal migration being produced by treatment with 12nM of either species. In each case this chemotactic response was almost completely antagonized by the addition of heparin. The importance of interaction between either native MCP-1 or MCP-1–SEAP and cell-surface GAGs for transcellular migration was demonstrated by the almost complete absence of leucocyte chemotaxis across monolayers of GAG-deficient mutant cells. In summary, this study shows that multimerization is neither necessary for, nor potentiates, the biological activity of MCP-1. However, the results do clearly demonstrate the importance of the interaction between MCP-1 and cell-surface heparan sulphate for transmonolayer leucocyte chemotaxis.
A Color Densitometer for Subtractive Processes<!--<xref ref-type="other" rid="fn1-10.5594_J12948">*</xref>--> (1938)

In subtractive color processes it is desirable to have some type of sensitometry to tell how the process departs from correct rendering of neutral gray scales. Reading the density of a color deposit through an arbitrary filler does not give rise to a useful value in terms of the final color process. For practical use the “effective density” of a color is defined as the visual density produced by adding sufficient of the other colors of the process to produce gray. An instrument is described that reads such values directly. This instrument is capable also of analyzing the amounts of each of two or more colors when present simultaneously and permits the analysis of a sensitometric exposure into the corresponding deposits of each color. Complete sensitometric curves may he drawn for all the records from the readings of a single strip.
AMIGene: Annotation of MIcrobial Genes (2003)

sbocs@genoscope.cns.fr).
Common channel signaling interface for local exchange carrier to interexchange carrier interconnection (1990)

Issues associated with the interconnection of common channel signaling (CCS) networks are identified. Protocol additions to support exchange access services are discussed. Possible extensions for circuit-switched services beyond basic exchange access, as well as further extensions of Signaling System No.7 to support non-circuit-associated signaling between carriers, are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Pyroelectric electron emission from nanometer-thick films of PbZrxTi1−xO3 (2013)

We report pyroelectric emission from PbZrxTi1−xO3 (PZT) thin films on nanometer-sharp tips. The epitaxial PZT films are 30 nm thick and grown directly on single-crystal silicon tips. Pyroelectric emission occurs for heating rates of ≥50 °C/min in a 20 V/μm external field. The emission current is a maximum of 240 nA when the heating rate is 100 °C/min and the electric field strength is ≥6.7 V/μm. The emitted charge is ∼7% of that expected for a perfect thin film emitter of epitaxial PbZrxTi1−xO3. We calculate that pyroelectric emission can occur without an applied field if the heating rate exceeds 4.0 × 107 °C/min.
A new antiarch placoderm from the Emsian (Early Devonian) of Wuding, Yunnan, China (2017)

Pan, Z., Zhu, M., Zhu, Y. & Jia, L., August 2017. A new antiarch placoderm from the Emsian (Early Devonian) of Wuding, Yunnan, China. Alcheringa 42, 10–21. ISSN 0311-5518.Wufengshania magniforaminis, a new genus and species of the Euantiarcha (Placodermi: Antiarcha), is described from the late Emsian (Early Devonian) of Wuding, Yunnan, southwestern China. The referred specimens were three-dimensionally preserved in black shales, allowing a high-resolution computed tomography reconstruction of anatomical details. The new euantiarch is characterized by a large orbital fenestra, an arched exoskeletal band around the orbital fenestra and a developed obtected nuchal area of the skull roof. Maximum parsimony analysis, using a revised data-set of antiarchs with 44 taxa and 66 characters, resolves Wufengshania gen. nov. as a member of the Bothriolepididae, which is characterized by the presence of the infraorbital sensory canal diverging on the lateral plate, and the nuchal plate with orbital facets. New analysis supports a sister group relationship between Dianolepis and the Bothriolepididae. Luquanolepis, a coeval euantiarch from the neighboring site of the new form, is referred to the Asterolepidoidei and represents the basalmost and earliest member of the Asterolepidoidei.Zhaohui Pan* [panzhaohui@ivpp.ac.cn], Min Zhu* [zhumin@ivpp.ac.cn], You'an Zhu† [zhuyouan@ivpp.ac.cn] and Liantao Jia [jialiantao@ivpp.ac.cn] Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, PO Box 643, Beijing 100044, PR China. *Also affiliated with University of Chinese Academy of Sciences, Beijing, 100049, PR China. †Also affiliated with Uppsala University, PO Box 256, 751 05 Uppsala, Sweden.
A Circuit Comparison System for Bipolar Linear LSI (1985)

This paper describes a new LST layout verification system which compares two circuits. One is extracted from LSI layout, and the other is an original circuit diagram. This system is also capable of giving layout error information to designers. In particular, this system is applicable to bipolar linear LSIs containing a variety electrical elements.
Protective Immunity to<i>Pseudomonas aeruginosa</i>Induced with a Capsid-Modified Adenovirus Expressing<i>P. aeruginosa</i>OprF (2007)

This study focuses on the development of a new clinical vaccine candidate (AdOprF.RGD.Epi8) against Pseudomonas aeruginosa using an E1(-) E3(-) adenovirus (Ad) vector expressing OprF (AdOprF.RGD.Epi8) and modifications of the Ad genome providing two capsid changes: (i) modification of the Ad hexon gene to incorporate an immune-dominant OprF epitope (Epi8) into loop 1 of the hexon, enabling repeat administration to boost the anti-OprF immune response, and (ii) modification of the fiber gene to incorporate an integrin-binding RGD sequence to enhance gene delivery to antigen-presenting cells. Western analysis confirmed that AdOprF.RGD.Epi8 expresses OprF, contains Epi8 in the hexon protein, and enhances gene transfer to dendritic cells compared to AdOprF, a comparable Ad vector expressing OprF with an unmodified capsid. Intramuscular immunization of C57BL/6 mice with AdOprF.RGD.Epi8 resulted in the generation of anti-OprF antibodies at comparable levels to those induced following immunization with AdOprF, but immunization with AdOprF.RGD.Epi8 was associated with increased CD4 and CD8 gamma interferon T-cell responses against OprF as well as increased survival against lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeat administration of AdOprF.RGD.Epi8 resulted in boosting of the humoral anti-OprF response as well as increased protection, whereas no boosting could be achieved with repeat administration of AdOprF. This suggests that the capsid-modified AdOprF.RGD.Epi8 vector is a more effective immunogen compared to a comparable wild-type Ad capsid, making it a good candidate for an anti-P. aeruginosa vaccine.
New aspects of vascular remodelling: the involvement of all vascular cell types (2005)

Conventionally, the architecture of arteries is based around the close-packed smooth muscle cells and extracellular matrix. However, the adventitia and endothelium are now viewed as key players in vascular growth and repair. A new dynamic picture has emerged of blood vessels in a constant state of self-maintenance. Recent work raises fundamental questions about the cellular heterogeneity of arteries and the time course and triggering of normal and pathological remodelling. A common denominator emerging in hypertensive remodelling is an early increase in adventitial cell density suggesting that adventitial cells drive remodelling and may initiate subsequent changes such as re-arrangement of smooth muscle cells and extracellular matrix. The organization of vascular smooth muscle cells follows regular arrangements that can be modelled mathematically. In hypertension, new patterns can be quantified in these terms and give insights to how structure affects function. As with smooth muscle, little is known about the organization of the vascular endothelium, or its role in vascular remodelling. Current observations suggest that there may be a close relationship between the helical organization of smooth muscle cells and the underlying pattern of endothelial cells. The function of myoendothelial connections is a topic of great current interest and may relate to the structure of the internal elastic lamina through which the connections must pass. In hypertensive remodelling this must present an organizational challenge. The objective of this paper is to show how the functions of blood vessels depend on their architecture and a continuous interaction of different cell types and extracellular proteins.