gebhart/patrepeval huggingface dataset:
Characterization of the Citrobacter freundii phoE gene and development of C. freundii-specific oligonucleotides (1992)

The phoE gene of Citrobacter freundii, encoding a pore-forming outer membrane protein, was cloned and its nucleotide sequence was determined. The homologies in terms of identical amino acids between the C. freundii PhoE protein and those of Escherichia coli, E. cloacae and Klebsiella pneumoniae were 90%, 86% and 84%, respectively. Two synthetic oligonucleotides, corresponding to hypervariable, cell surface-exposed regions of the protein, were tested for their specificity in polymerase chain reactions. They were specific for the species C. freundii, i.e., no reaction was detected with 35 non-C. freundii strains tested, including 17 Salmonella, two C. amalonaticus and three C. diversus strains, whereas all five C. freundii strains tested were correctly recognized.
Novel 2',5'-oligoadenylates synthesized in interferon-treated, vaccinia virus-infected cells (1985)

2-5A[ppp(A2'p)nA] and related materials accumulate to greater than micromolar concentrations in vaccinia virus-infected HeLa cells and in interferon-treated, vaccinia-infected HeLa, CV1, and L929 cells even when virus replication is not inhibited. A variably complex mixture of authentic 2-5A (n = 2 to 4), nonphosphorylated cores [(A2'p)nA; n = 2 to 5], and additional compounds of unknown structure was observed.
Binding Site Elucidation of Hydantoin-Based Antagonists of LFA-1 Using Multidisciplinary Technologies:  Evidence for the Allosteric Inhibition of a Protein−Protein Interaction (2001)

The binding site on the lymphocyte function-associated antigen-1 (LFA-1) of a class of hydantoin-based antagonists of leukocyte cell adhesion has been identified. This site resides in the inserted-domain (I-domain) of the CD11a chain at a location that is distal to residues known to be required for interactions with the intercellular adhesion molecules. This finding supports the hypothesis that the molecules are antagonizing cell adhesion via an allosteric modification of LFA-1. The binding site was identified using an integrated immunochemical, chemical, and molecular modeling approach. Antibodies that map to epitopes on the I-domain were blocked from binding to the purified protein by the hydantoins, indicating that the hydantoin-binding site resides on the I-domain. Photoaffinity labeling of the I-domain followed by LC/MS and LC/MS/MS analysis of the enzymatic digest identified proline 281 as the primary amino acid residue covalently attached to the photoprobe. Distance constraints derived from this study coupled with known SAR considerations allowed for the construction of a molecular model of the I-domain/inhibitor complex. The atomic details of the protein/antagonist interaction were accurately predicted by this model, as subsequently confirmed by the X-ray crystal structure of the complex.
Human keratinocytes produce but do not process pro-interleukin-1 (IL-1) beta. Different strategies of IL-1 production and processing in monocytes and keratinocytes. (1991)

Keratinocytes comprise the majority of cells in the epidermis, the interleukin-1 rich layer of tissue contiguous with the outside world. Keratinocytes produce IL-1 alpha and beta mRNA in vitro, but only IL-1 alpha biological activity has been identified in keratinocyte cultures. In contrast, monocytes secrete biological activities attributable to both species of IL-1. Using several monoclonal antibodies to IL-1 beta, significant amounts of IL-1 beta protein could be found in keratinocyte cultures; all of this immunoreactive IL-1 beta was in the 31-kD form. This latent cytokine has been shown to bind inefficiently to the IL-1 receptor and to be (in relative terms) biologically inactive. Chymotrypsin cleaves 31-kD IL-1 beta at Tyr 113-Val 114, generating an 18-kD IL-1 species with activity equivalent to the authentic mature IL-1 beta (NH2-terminal Ala 117). Treatment of 31-kD keratinocyte IL-1 beta with chymotrypsin also generated an 18-kD molecule and significant IL-1 activity. Monocytes contain an IL-1 convertase enzyme that cleaves the IL-1 beta promolecule at Ala 117. We demonstrate here that keratinocytes do not contain such an IL-1 convertase activity, nor do they contain any activity capable of productively processing 31-kD IL-1 beta into a biologically active form. These data suggest that keratinocytes (and other non-bone marrow-derived cells) produce IL-1 beta in an inactive form that can be processed only after leaving the cell.
Preclinical PET Study of Intravitreal Injections. (2017)

Intravitreal pharmacokinetic studies based on the use of dedicated PET imaging can be of potential interest as noninvasive tools in ophthalmic drug development in small animals.
Infrared Spectra of Organic Azides (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInfrared Spectra of Organic AzidesEugene. Lieber, C. N. R. Rao, T. S. Chao, and C. W. W. HoffmanCite this: Anal. Chem. 1957, 29, 6, 916–918Publication Date (Print):June 1, 1957Publication History Published online1 May 2002Published inissue 1 June 1957https://pubs.acs.org/doi/10.1021/ac60126a016https://doi.org/10.1021/ac60126a016research-articleACS PublicationsRequest reuse permissionsArticle Views7710Altmetric-Citations121LEARN 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
Multiple Vacuolar Sorting Determinants Exist in Soybean 11S Globulin (2006)

The sorting determinants of glycinin, a soybean (Glycine max) 11S globulin, which mediates protein targeting to the protein storage vacuole (PSV), were investigated in maturing soybean cotyledons by transient expression assays. A C-terminal stretch of 10 amino acids of A1aB1b, a glycinin group I subunit, was sufficient to direct green fluorescent protein (GFP) to the PSV. This peptide may correspond to a C-terminal vacuolar sorting determinant (ctVSD). Because functional inhibition of this putative ctVSD of A1aB1b did not block PSV sorting of A1aB1b, we used the three-dimensional structure of A1aB1b to identify candidates for a sequence-specific determinant (ssVSD). We found that the sequence downstream of disordered region 4 could direct GFP to the PSV and that Ile-297 is critical for sorting. However, functional inhibition of the ctVSD, combined with the Ile297Gly mutation, did not abolish the vacuolar sorting of A1aB1b, suggesting that A1aB1b has a third sorting determinant in addition to ctVSD and ssVSD. A glycinin group II subunit, A3B4, lacked a ctVSD but contained a VSD reminiscent of an ssVSD and an additional sorting determinant. We also demonstrate, by expression of dominant negative mutants of small GTPases and drug treatment experiments, that the trafficking of A1aB1b is COPII vesicle-dependent and wortmannin- and brefeldin A-sensitive.
Lipid-Regulated Kinases: Some Common Themes at Last (1998)

One ubiquitous and very important signaling molecule inside cells is the phosphorylated lipid PtdIns(3,4,5)P. The biochemical pathways that deliver the signals from this lipid contain kinases (which add phosphates to other molecules) with regulatory properties that have seemed impossibly complex and diverse. In his commentary, Downward describes how new results reported in this week9s issue of Science (
 Pullen
 et al.
 and
 Stephens
 et al.) and in
 Current Biology
 reveal that two of these kinases are actually regulated similarly, lending some welcome common themes to these pathways.
Diphosphoryl lipid A obtained from the nontoxic lipopolysaccharide of Rhodopseudomonas sphaeroides is an endotoxin antagonist in mice (1991)

Diphosphoryl lipid A (DPLA) obtained from the nontoxic lipopolysaccharide (LPS) of Rhodopseudomonas sphaeroides ATCC 17023 did not induce interleukin-1 release by murine peritoneal macrophages. However, it blocked this induction by toxic deep-rough chemotype LPS (ReLPS) from Escherichia coli D31m4. Previously, we obtained similar results on the induction of tumor necrosis factor (TNF) by macrophages. These results showed that DPLA is able to block in vitro the induction of two important mediators of gram-negative bacterial sepsis. We then wanted to determine whether DPLA could also block the induction of TNF by LPS in animals. Mice were treated with 100 micrograms of R. sphaeroides DPLA and challenged 60 min later with 1.0 micrograms of ReLPS from E. coli. The serum TNF level was measured after 60 min. Treatment of mice with this DPLA blocked the rapid and transient rise of TNF caused by ReLPS. This result suggested that R. sphaeroides DPLA might be able to protect animals against endotoxin shock caused by gram-negative bacterial infection.
Investigation of the pore-forming mechanism of a cytolytic δ-endotoxin from Bacillus thuringiensis (2003)

Cyt2Aa1 is a cytolytic protein produced by Bacillus thuringiensis subsp. kyushuensis. Penetration of the toxin into membranes has been studied to learn more about membrane-insertion mechanisms and transmembrane-pore formation. The haemolysis assay of Cyt2Aa1 showed a steep and sigmoidal dose-response curve, indicating that toxin aggregation or oligomerization is required for pore formation. Studies of the effect of temperature on pore formation and fluorimetric studies of acrylodan-labelled toxin suggest that toxin inserts into the membrane before oligomerizing to form a pore. Low temperature neither inhibited membrane binding nor closed pores that have been formed, but markedly inhibited oligomerization of the toxin molecules. When toxin-treated red blood cells at 4 degrees C were transferred to a toxin-free solution at 37 degrees C, no significant increase in haemolysis was observed. This result suggests that membrane-bound toxin could not diffuse laterally and interact with other molecules to form a pore. From these results, we propose that Cyt2Aa1 binds and inserts into the membrane as a monomer. Oligomerization occurs when toxin molecules have bound in close proximity to each other and pores are formed from large oligomers.
Characterization of promoter expression patterns derived from the Pht1 phosphate transporter genes of barley (Hordeum vulgare L.) (2004)

By comparison with dicot plant species, relatively little work has been reported on the phosphate transporter (Pht1) gene family from monocot species. Initial studies have shown that barley contains at least eight homologous genes. The promoters of six of these genes were analysed for the presence of regulatory elements potentially associated with expression specificity. In particular, the P1BS-like elements (implicated in phosphorus-regulated expression of genes in plants) was identified in all HvPht1 promoters examined. For two members of the family (HvPht1;1 and HvPht1;2), promoter fusions to beta-glucuronidase and green fluorescent protein reporter genes were constructed, transformed into rice, and the expression profiles observed. The inclusion of an intron derived from Adh1 enhanced gene expression approximately 20-fold, but did not appear to affect the specificity of expression. The HvPht1;1 and HvPht1;2 promoters showed minor differences in expression patterns but, in general, expression was observed at high levels in trichoblast cells (root hairs) and stele of the nodal root, throughout secondary roots, and at a relatively low level in leaf tissues. Under phosphorus deficiency, expression was induced by up to 5-fold. These observations are consistent with a primary role for the encoded genes in the uptake of phosphate by root hairs from soil solution and further current understanding of the mechanisms involved. The promoters also have application for providing a new resource for cereal transformation, ideally suited for driving the expression of foreign genes associated with nutrient uptake.
Phosphatidylinositol-Dependent Membrane Fusion Induced by a Putative Fusogenic Sequence of Ebola Virus (1998)

The membrane-interacting abilities of three sequences representing the putative fusogenic subdomain of the Ebola virus transmembrane protein have been investigated. In the presence of calcium, the sequence EBO(GE) (GAAIGLAWIPYFGPAAE) efficiently fused unilamellar vesicles composed of phosphatidylcholine, phosphatidylethanolamine, cholesterol, and phosphatidylinositol (molar ratio, 2:1:1:0.5), a mixture that roughly resembles the lipid composition of the hepatocyte plasma membrane. Analysis of the lipid dependence of the process demonstrated that the fusion activity of EBO(GE) was promoted by phosphatidylinositol but not by other acidic phospholipids. In comparison, EBO(EA) (EGAAIGLAWIPYFGPAA) and EBO(EE) (EGAAIGLAWIPYFGPAAE) sequences, which are similar to EBO(GE) except that they bear the negatively charged glutamate residue at the N terminus and at both the N and C termini, respectively, induced fusion to a lesser extent. As revealed by binding experiments, the glutamate residue at the N terminus severely impaired peptide-vesicle interaction. In addition, the fusion-competent EBO(GE) sequence did not associate significantly with vesicles lacking phosphatidylinositol. Tryptophan fluorescence quenching by vesicles containing brominated phospholipids indicated that the EBO(GE) peptide penetrated to the acyl chain level only when the membranes contained phosphatidylinositol. We conclude that binding and further penetration of the Ebola virus putative fusion peptide into membranes might be governed by the nature of the N-terminal residue and by the presence of phosphatidylinositol in the target membrane. Moreover, since insertion of such a peptide leads to membrane destabilization and fusion, the present data would be compatible with the involvement of this sequence in Ebola virus fusion.
Endosomal processing for antigen presentation mediated by CD1 and Class I major histocompatibility complex: roads to display or destruction (2009)

The presentation of antigen in a form that can be recognized by T lymphocytes of the immune system requires antigen processing and association of antigen-derived fragments with molecules encoded by the major histocompatibility complex (MHC) locus or by the CD1 locus. Much emphasis on antigen processing and presentation in the last decades has focused on what we consider 'conventional routes' of antigen processing and presentation, whereby extracellular antigens are processed for presentation via Class II MHC complexes and cytosolic antigens are presented as peptide-Class I MHC complexes. We here highlight two other pathways in myeloid dendritic cells, those of lipid antigen presentation in association with CD1 and of peptide cross-presentation via Class I MHC complexes. Some pathogens evade immune recognition through inhibition of antigen presentation of phagosomal origin. Deviations in endosomal antigen processing and presentation are also seen in individuals suffering from glycosphingolipid lysosomal lipid storage diseases. We summarize recent developments in the endosomal antigen processing and presentation pathway, for display as lipid-CD1 complexes to natural killer T cells and as peptide-Class I MHC complexes to CD8 T cells.
Analysis of the Minimal Amyloid-forming Fragment of the Islet Amyloid Polypeptide (2001)

The development of type II diabetes was shown to be associated with the formation of amyloid fibrils consisted of the islet amyloid polypeptide (IAPP or amylin). Recently, a short functional hexapeptide fragment of IAPP (NH(2)-NFGAIL-COOH) was found to form fibrils that are very similar to those formed by the full-length polypeptide. To better understand the specific role of the residues that compose the fragment, we performed a systematic alanine scan of the IAPP "basic amyloidogenic units." Turbidity assay experiments demonstrated that the wild-type peptide and the Asn(1) --> Ala and Gly(3) --> Ala peptides had the highest rate of aggregate formation, whereas the Phe(2) --> Ala peptide did not form any detectable aggregates. Dynamic light-scattering experiments demonstrated that all peptides except the Phe(2) --> Ala form large multimeric structures. Electron microscopy and Congo red staining confirmed that the structures formed by the various peptides are indeed amyloid fibrils. Taken together, the results of our study provide clear experimental evidence for the key role of phenylalanine residue in amyloid formation by IAPP. In contrast, glycine, a residue that was suggested to facilitate amyloid formation in other systems, has only a minor role, if any, in this case. Our results are discussed in the context of the remarkable occurrence of aromatic residues in short functional fragments and potent inhibitors of amyloid-related polypeptides. We hypothesize that pi-pi interactions may play a significant role in the molecular recognition and self-assembly processes that lead to amyloid formation.
Longitudinal data analysis using generalized linear models (1986)

This paper proposes an extension of generalized linear models to the analysis of longitudinal data. We introduce a class of estimating equations that give consistent estimates of the regression parameters and of their variance under mild assumptions about the time dependence. The estimating equations are derived without specifying the joint distribution of a subject's observations yet they reduce to the score equations for multivariate Gaussian outcomes. Asymptotic theory is presented for the general class of estimators. Specific cases in which we assume independence, m-dependence and exchangeable correlation structures from each subject are discussed. Efficiency of the proposed estimators in two simple situations is considered. The approach is closely related to quasi-likelihood.
Self-ordering Regimes of Porous Alumina:  The 10 Porosity Rule (2002)

Transmission electron microscopy analysis of self-ordered porous alumina obtained by electrochemical anodization shows that self-ordering requires a porosity of 10%, independent of the specific anodization conditions. This corresponds to a volume expansion of alumina to aluminum of about 1.2. We propose that self-ordering of porous alumina with any interpore distance is possible if the applied potential, which mainly determines the interpore distance, and the pH value of the electrolyte, which mainly defines the pore radius, match the 10% porosity rule.
Optimal conditions for genetic transformation of the cyanobacterium Anacystis nidulans R2 (1984)

Under optimal conditions, the cyanobacterium Anacystis nidulans R2 was transformed to ampicillin resistance at frequencies of greater than 10(7) transformants per microgram of plasmid (pCH1) donor DNA. No stringent period of competency was detected, and high frequencies of transformation were achieved with cultures at various growth stages. Transformation increased with time after addition of donor DNA up to 15 to 18 h. The peak of transformation efficiency (transformants/donor molecule) occurred at plasmid concentrations of 125 to 325 ng/ml with an ampicillin resistance donor plasmid (pCH1) and 300 to 625 ng/ml for chloramphenicol resistance conferred by plasmid pSG111. The efficiency of transformation was enhanced by excluding light during the incubation or by blocking photosynthesis with the electron transport inhibitor 3-(3, 4-dichlorophenyl)-1, 1-dimethylurea (DCMU) or the uncoupler carbonyl cyanide-m-chlorophenyl hydrazone. Preincubation of cells in darkness for 15 to 18 h before addition of donor DNA significantly decreased transformation efficiency. Growth of cells in iron-deficient medium before transformation enhanced efficiency fourfold. These results were obtained with selection for ampicillin (pCH1 donor plasmid)- or chloramphenicol (pSG111 donor plasmid)-resistant transformants. Approximately 1,000 transformants per microgram were obtained when chromosomal DNA from an herbicide (DCMU)-resistant mutant was used as donor DNA. DCMU resistance was also transferred to recipient cells by using restriction fragments of chromosomal DNA from DCMU-resistant mutants. This procedure allowed size classes of fragments to be assayed for the presence of the DCMU resistance gene.
Long-term effects of dietary calcium on risk markers for colon cancer in patients with familial polyposis. (1990)

There is conflicting evidence regarding the benefit of calcium in prevention of colon cancer. Patients who have undergone ileorectal operations for familial polyposis can be useful to study hypotheses on prevention of colon cancer. In this study we evaluated the effect of long-term calcium supplementation on risk markers of colon cancer. Thirty-one patients with familial polyposis, after subtotal colectomy, were randomized to group A, which received placebo, and group B, which received 1200 mg of calcium daily. Intervention lasted 9 months, in which they underwent four 3-monthly evaluations that included food records, fecal pH, calcium and bile acids, and rectal biopsy for thymidine labeling. Age, height, weight, macronutrients, and dietary fiber were comparable in both groups. More women were in the group that received placebo. Fecal pH, weight, and bile acid levels were similar before intervention and remained unchanged. Fecal calcium levels were similar before intervention and increased in the calcium group throughout the study (p less than 0.05). Labeling index of placebo and calcium groups was similar before intervention (4.8 and 6.1, respectively). After 3 months it was reduced in both groups (3.1 and 4.4, respectively; p less than 0.05). After 6 months it was reduced only in the calcium group (3.4; p less than 0.05). After 9 months it did not differ from the starting point (3.4 and 4.0, respectively). In a long-term intervention study with a homogenous group of patients with familial polyposis, supplemental dietary calcium did not affect mucosal risk factors for colon cancer.
Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse. (1979)

Use of the specific-locus test to measure the frequency of transmitted gene mutations induced in mouse spermatogonia has shown ethylnitrosourea to be by far the most potent mutagen yet discovered in the mouse. The dose used, 250 mg/kg, gave a mutation rate 5 times as high as had been obtained with 600 R, the most effective acute dose of x-rays. Compared to procarbazine, heretofore the most mutagenic chemical known in the mouse, ethylnitrosourea proved to be 15 times more mutagenic than the peak effect obtained with the most effective dose of procarbazine. Because of its high mutagenicity, ethylnitrosourea can serve as a model compound in exploring the effect of such factors as dose response, dose fractionation, sex, and cell stage on the mutagenic action of a chemical. Ethylnitrosourea is clearly the mutagen of choice for the production of any kind of desired new gene mutations in the mouse.