gebhart/patrepeval huggingface dataset:
IL-4-Induced Selective Clearance of Oligomeric β-Amyloid Peptide1–42 by Rat Primary Type 2 Microglia (2008)

A hallmark of immunopathology associated with Alzheimer's disease is the presence of activated microglia (MG) surrounding senile plaque deposition of beta-amyloid (Abeta) peptides. Abeta peptides are believed to be potent activators of MG, which leads to Alzheimer's disease pathology, but the role of MG subtypes in Abeta clearance still remains unclear. In this study, we found that IL-4 treatment of rat primary-type 2 MG enhanced uptake and degradation of oligomeric Abeta(1-42) (o-Abeta(1-42)). IL-4 treatment induced significant expression of the scavenger receptor CD36 and the Abeta-degrading enzymes neprilysin (NEP) and insulin-degrading enzyme (IDE) but reduced expression of certain other scavenger receptors. Of cytokines and stimulants tested, the anti-inflammatory cytokines IL-4 and IL-13 effectively enhanced CD36, NEP, and IDE. We demonstrated the CD36 contribution to IL-4-induced Abeta clearance: Chinese hamster ovary cells overexpressing CD36 exhibited marked, dose-dependent degradation of (125)I-labeled o-Abeta(1-42) compared with controls, the degradation being blocked by anti-CD36 Ab. Also, we found IL-4-induced clearance of o-Abeta(1-42) in type 2 MG from CD36-expressing WKY/NCrj rats but not in cells from SHR/NCrj rats with dysfunctional CD36 expression. NEP and IDE also contributed to IL-4-induced degradation of Abeta(1-42), because their inhibitors, thiorphan and insulin, respectively, significantly suppressed this activity. IL-4-stimulated uptake and degradation of o-Abeta(1-42) were selectively enhanced in type 2, but not type 1 MG that express CD40, which suggests that the two MG types may play different neuroimmunomodulating roles in the Abeta-overproducing brain. Thus, selective o-Abeta(1-42) clearance, which is induced by IL-4, may provide an additional focus for developing strategies to prevent and treat Alzheimer's disease.
Expression of Frizzled5, Frizzled7, and Frizzled10 during early mouse development and interactions with canonical Wnt signaling (2007)

Wnt signaling has been shown to be important in the patterning of the gastrulating mouse embryo, especially in axis formation. To this date, there is no clear indication that the Wnt receptors, Frizzleds (Fzds), are involved in such early specification. Moreover, at the gastrulation stage, the only Fzd with a known characterized expression pattern is Fzd8, which is expressed in the anterior visceral endoderm (aVE) (Lu et al. [2004] Gene Expr Patterns 4:569-572). Following a real time RT-PCR study to evaluate Fzd expression in the gastrulating embryo, we used whole-mount in situ hybridization to reveal new expression domains for Fzd5, Fzd7, and Fzd10. Fzd5 is expressed in the aVE and Fzd7 expression is restricted to the epiblast of the gastrulating embryo. The expression pattern of Fzd10 in the primitive streak of the gastrula suggests it has a role in mesoderm induction. We also show that the purified, secreted forms of the extracellular cysteine-rich domains (CRDs) of FZD5, Fzd7, and Fzd8 can antagonize Wnt3a-induced beta-Catenin accumulation in L-cells, whereas in mouse embryonic stem cells, these CRDs can inhibit spontaneous mesoderm formation and promote neural differentiation. Our data demonstrate that Fzd5, Fzd7, and Fzd10 are expressed in distinct domains of the gastrulating embryo, and that the CRDs of FZD5, Fzd7, and Fzd8 can regulate Wnts, indicating that Fzds interpret Wnt signals during embryonic mesoderm and neural induction.
Age-related oxidative changes in pancreatic islets are predominantly located in the vascular system (2017)

Aged tissues usually show a decreased regenerative capacity accompanied by a decline in functionality. During aging pancreatic islets also undergo several morphological and metabolic changes. Besides proliferative and regenerative limitations, endocrine cells lose their secretory capacity, contributing to a decline in functional islet mass and a deregulated glucose homeostasis. This is linked to several features of aging, such as induction of cellular senescence or the formation of modified proteins, such as advanced glycation end products (AGEs) - the latter mainly examined in relation to hyperglycemia and in disease models. However, age-related changes of endocrine islets under normoglycemic and non-pathologic conditions are poorly investigated. Therefore, a characterization of pancreatic tissue sections as wells as plasma samples of wild-type mice (C57BL/6J) at various age groups (2.5, 5, 10, 15, 21 months) was performed. Our findings reveal that mice at older age are able to secret sufficient amounts of insulin to maintain normoglycemia. During aging the pancreatic islet area increased and the islet size doubled in 21 months old mice when compared to 2.5 months old mice, whereas the islet number was unchanged. This was accompanied by an age-dependent decrease in Ki-67 levels and pancreatic duodenal homeobox-1 (PDX-1), indicating a decline in proliferative and regenerative capacity of pancreatic islets with advancing age. In contrast, the number of p16<sup>Ink4a</sup>-positive nuclei within the islets was elevated starting from 10 months of age. Interestingly, AGEs accumulated exclusively in the islet blood vessels of old mice associated with increased amounts of inflammatory markers, such as the inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine (3-NT). In summary, the age-related increase in islet size and area was associated with the induction of senescence, accompanied by an accumulation of non-enzymatically modified proteins in the islet vascular system.
Expanding the Substrate Repertoire of a DNA Polymerase by Directed Evolution (2004)

Nucleic acid polymerases are the most important reagents in biotechnology. Unfortunately, their high substrate specificity severely limits their applications. Polymerases with tailored substrate repertoires would significantly expand their potential and allow enzymatic synthesis of unnatural polymers for in vivo and in vitro applications. For example, the ability to synthesize 2'-O-methyl-modified polymers would provide access to materials possessing properties that make them attractive for biotechnology and therapeutic applications, but unfortunately, no known polymerases are capable of efficiently accepting these modified substrates. To evolve such enzymes, we have developed an activity-based selection method which isolates polymerase mutants with the desired property from libraries of the enzyme displayed on phage. In this report, mutants that could efficiently synthesize an unnatural polymer from 2'-O-methyl ribonucleoside triphosphates were immobilized and isolated by means of their activity-dependent modification of a DNA oligonucleotide primer attached to the same phage particle. In each case, directed evolution resulted in relocating a critical side chain to a different position in the polypeptide, thus re-engineering the overall active site while preserving critical protein-DNA interactions. Remarkably, one evolved polymerase is shown to incorporate the modified substrates with an efficiency and fidelity equivalent to that of the wild-type enzyme with natural substrates.
Pose Embeddings: A Deep Architecture for Learning to Match Human Poses (2015)

We present a method for learning an embedding that places images of humans in similar poses nearby. This embedding can be used as a direct method of comparing images based on human pose, avoiding potential challenges of estimating body joint positions. Pose embedding learning is formulated under a triplet-based distance criterion. A deep architecture is used to allow learning of a representation capable of making distinctions between different poses. Experiments on human pose matching and retrieval from video data demonstrate the potential of the method.
Color-still videophone terminal for ISDN (1989)

A color still videophone terminal for ISDN has been developed. This paper describes that the terminal uses an adaptive discrete cosine transform (ADCT) coding method, and features picture quality and external video camera control capabilities.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
C. difficile toxin A increases intestinal permeability and induces Cl- secretion (1990)

Mucosal sheets of guinea pig ileum mounted in Ussing chambers were used to determine effects of highly purified Clostridium difficile toxin A on intestinal structure and barrier function in the absence of recruited neutrophils and blood flow. With the use of standard electrophysiological and morphological techniques, our results indicate that 5 micrograms/ml mucosal toxin A induces substantial alteration in epithelial permeability and in structure of absorptive cells. Transepithelial fluxes of mannitol (3.6 A) and inulin (11.5 A) increased 20-80 min after toxin A exposure (63 +/- 13 vs. 149 +/- 14 and 2.33 +/- 0.43 vs. 7.03 +/- 1.0 nmol.cm-2.h-1 for mannitol and inulin; controls vs. toxin exposed, respectively, both P less than 0.01). Toxin A exposure diminished short-circuit current (153 +/- 8 vs. 77 +/- 6 microA/cm2 for control and toxin exposed, respectively, P less than 0.001), decreased transepithelial electrical resistance (61.6 +/- 3 vs. 50.1 +/- 3.9 omega.cm2 for control and toxin exposed, respectively, P less than 0.05), increased passive permeation of Na+ (19.1 +/- 0.9 vs. 27.4 +/- 0.9 mumol.cm-2.h-1 for control and toxin exposed, respectively), and induced a Cl- secretory response (net flux 3.65 +/- 3.0 vs. -4.62 +/- 2.6 mumol.cm-2.h-1, for control and toxin exposed, respectively, P less than 0.05) over the 2-h experimental time course. Toxin A-induced structural alterations of villus tip absorptive cells were strikingly similar to those induced by the actin-binding agent cytochalasin D. Specifically, cells displayed constricted subjunctional zones, flared microvillus brush borders, condensation of microfilaments in the zone of the perijunctional actomyosin ring, and breakdown of intercellular tight junctions.(ABSTRACT TRUNCATED AT 250 WORDS)
γ-Pyridones by Isomerization. Substituted 1-Methyl-3,5-dibenzyl-4-pyridones (1955)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTγ-Pyridones by Isomerization. Substituted 1-Methyl-3,5-dibenzyl-4-pyridonesNelson J. Leonard and David M. LockeCite this: J. Am. Chem. Soc. 1955, 77, 7, 1852–1855Publication Date (Print):April 1, 1955Publication History Published online1 May 2002Published inissue 1 April 1955https://pubs.acs.org/doi/10.1021/ja01612a042https://doi.org/10.1021/ja01612a042research-articleACS PublicationsRequest reuse permissionsArticle Views140Altmetric-Citations30LEARN 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
The Arabidopsis Photomorphogenic Mutant hy1 Is Deficient in Phytochrome Chromophore Biosynthesis as a Result of a Mutation in a Plastid Heme Oxygenase (1999)

The HY1 locus of Arabidopsis is necessary for phytochrome chromophore biosynthesis and is defined by mutants that show a long hypocotyl phenotype when grown in the light. We describe here the molecular cloning of the HY1 gene by using chromosome walking and mutant complementation. The product of the HY1 gene shows significant similarity to animal heme oxygenases and contains a possible transit peptide for transport to plastids. Heme oxygenase activity was detected in the HY1 protein expressed in Escherichia coli. Heme oxygenase catalyzes the oxygenation of heme to biliverdin, an activity that is necessary for phytochrome chromophore biosynthesis. The predicted transit peptide is sufficient to transport the green fluorescent protein into chloroplasts. The accumulation of the HY1 protein in plastids was detected by using immunoblot analysis with an anti-HY1 antiserum. These results indicate that the Arabidopsis HY1 gene encodes a plastid heme oxygenase necessary for phytochrome chromophore biosynthesis.
Carotenoid-Related Alteration of Cell Membrane Fluidity Impacts Staphylococcus aureus Susceptibility to Host Defense Peptides (2010)

Carotenoid pigments of Staphylococcus aureus provide integrity to its cell membrane (CM) and limit oxidative host defense mechanisms. However, the role of carotenoids in staphylococcal resistance to nonoxidative host defenses has not been characterized. The current study examined the relationship among CM carotenoid content, membrane order, and in vitro susceptibility to daptomycin or to prototypic neutrophil-derived, platelet-derived, or bacterium-derived cationic antimicrobial peptides (human neutrophil defensin-1 [hNP-1], platelet microbicidal proteins [PMPs], or polymyxin B, respectively). A previously characterized methicillin-susceptible Staphylococcus aureus (MSSA) isogenic clinical strain set was used, including a parental isolate with an intact carotenoid biosynthetic operon (crtOPQMN) containing the crtM gene encoding early steps in staphyloxanthin biosynthesis, a crtM deletion mutant, and a crtMN multicopy plasmid-complemented variant. Compared to the parental and crtM knockout strains, the crtMN-complemented strain exhibited (i) increased carotenoid production, (ii) increased CM rigidity (P < 0.001), and (iii) uniformly reduced susceptibility to killing by the above-mentioned range of cationic peptides (statistically significant for hNP-1 [20 μg/ml]; P = 0.0037). There were no significant differences in phospholipid composition and asymmetry, fatty acid profiles, surface charge, or cell wall thickness among the strain set. Collectively, these data support the concept that carotenoid biosynthesis can contribute to the ability of S. aureus to subvert nonoxidative host defenses mediated by cationic peptides, potentially by increasing target membrane rigidity.
Stilbene Synthase from Seedlings ofPinus sylvestris: Purification and Induction in Response to Fungal Infection (1990)

We describe here the purification and partial characterization of a new stilbene synthase whose activity is dramatically increased upon stress. Some of the stress conditions used, especially the biotic signals originating from fungal cells, mimic situations of physiological relevance under environmental conditions
Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line. (1989)

A novel basic heparin-binding monocyte chemotactic factor (MCF) was purified to homogeneity from the conditioned media of human myelomonocytic cell line THP-1 based on its in vitro monocyte chemotactic activity. The purified MCF was homogenous and estimated to be 15 kD on SDS-PAGE. Purified MCF stimulated normal human monocytes to be growth inhibitory in vitro at 2-3 d for several human tumor cell lines. This represents the first report of the identification and purification of a chemoattractant cytokine that also activates monocytes but is distinct from interferons and other known cytokines.
Chemiluminescent Detection of Oxidants in Vascular Tissue (1999)

Lucigenin-amplified chemiluminescence has frequently been used to assess the formation of superoxide in vascular tissues. However, the ability of lucigenin to undergo redox cycling in purified enzyme-substrate mixtures has raised questions concerning the use of lucigenin as an appropriate probe for the measurement of superoxide production. Addition of lucigenin to reaction mixtures of xanthine oxidase plus NADH resulted in increased oxygen consumption, as well as superoxide dismutase-inhibitable reduction of cytochrome c, indicative of enhanced rates of superoxide formation. Additionally, it was revealed that lucigenin stimulated oxidant formation by both cultured bovine aortic endothelial cells and isolated rings from rat aorta. Lucigenin treatment resulted in enhanced hydrogen peroxide release from endothelial cells, whereas exposure to lucigenin resulted in inhibition of endothelium-dependent relaxation in isolated aortic rings that was superoxide dismutase inhibitable. In contrast, the chemiluminescent probe coelenterazine had no significant effect on xanthine oxidase-dependent oxygen consumption, endothelial cell hydrogen peroxide release, or endothelium-dependent relaxation. Study of enzyme and vascular systems indicated that coelenterazine chemiluminescence is a sensitive marker for detecting both superoxide and peroxynitrite.
On the Chemical Sterilization of Blood and Blood Plasma. (1949)

Methyl-bis (beta-chloroethyl) amine hydrochloride has been demonstrated to exert effective virucidal and bactericidal effects in the presence of either plasma, serum or whole blood. The required virucidal dosage of HN2 is below 500 mg/l of blood or plasma if the pH is at or near 7.0. The end products of decomposition of the added HN2 are essentially nontoxic if the pH of the system is not too low. No evidence of antigenic or other toxic reactions has been produced in two dogs and two humans receiving repeated injections of treated plasma. Human red blood cells withstand the application of virucidal dosages of HN2 without hemolysis and with only a slight increase in fragility. Complement, immune bodies, phosphatase and fibrinogen are only slightly affected by sterilizing dosages of HN2. Prothrombin time is markedly prolonged by HN2.
The Tumor-Associated Variant RAD51 G151D Induces a Hyper-Recombination Phenotype (2016)

The RAD51 protein plays a key role in the homology-directed repair of DNA double-strand breaks and is important for maintaining genome stability. Here we report on a novel human RAD51 variant found in an aggressive and therapy-refractive breast carcinoma. Expression of the RAD51 G151D variant in human breast epithelial cells increases the levels of homology-directed repair. Expression of RAD51 G151D in cells also promotes high levels of chromosomal aberrations and sister chromatid exchanges. In vitro, the purified RAD51 G151D protein directly and significantly enhances DNA strand exchange activity in the presence of RPA. In concordance with this result, co-incubation of G151D with BRCA2 resulted in a much higher level of strand-exchange activity compared to WT RAD51. Strikingly, the RAD51 G151D variant confers resistance to multiple DNA damaging agents, including ionizing radiation, mitomycin C, and doxorubicin. Our findings demonstrate that the RAD51 G151D somatic variant has a novel hyper-recombination phenotype and suggest that this property of the protein is important for the repair of DNA damage, leading to drug resistance.
Presenilin 1 interaction in the brain with a novel member of the Armadillo family (1997)

One approach to understanding the function of presenilin 1 (PS1), is to discover those proteins with which it interacts. Evidence for a function in developmental patterning came from C. elegans, in which a PS homologue was identified by screening for suppressors of a mutation in Notch/lin-12, a gene which specifies cell fate. However, this genetic experiment cannot determine which proteins directly interact with PS1. Therefore, we utilized the two hybrid system and confirmatory co-immunoprecipitations to identify a novel catenin, termed delta-catenin, which interacts with PS1 and is principally expressed in brain. The catenins are a gene family related to the Armadillo gene in Drosophila, some of which appear to have dual roles-they are components of cell-cell adherens junctions, and may serve as intermediates in the Wingless (Wg) signaling pathway, which, like Notch/lin-12, is also responsible for a variety of inductive signaling events. In the non-neuronal 293 cell line, PS1 interacted with beta-catenin, the family member with the greatest homology to Armadillo. Wg and Notch interactions are mediated by the Dishevelled gene, which may form a signaling complex with PS1 and Wg pathway intermediates to regulate the function of the Notch/lin-12 gene.
Random-access rendering of general vector graphics (2008)

We introduce a novel representation for random-access rendering of antialiased vector graphics on the GPU, along with efficient encoding and rendering algorithms. The representation supports a broad class of vector primitives, including multiple layers of semitransparent filled and stroked shapes, with quadratic outlines and color gradients. Our approach is to create a coarse lattice in which each cell contains a variable-length encoding of the graphics primitives it overlaps. These cell-specialized encodings are interpreted at runtime within a pixel shader. Advantages include localized memory access and the ability to map vector graphics onto arbitrary surfaces, or under arbitrary deformations. Most importantly, we perform both prefiltering and supersampling within a single pixel shader invocation, achieving inter-primitive antialiasing at no added memory bandwidth cost. We present an efficient encoding algorithm, and demonstrate high-quality real-time rendering of complex, real-world examples.
Early administration of branched-chain amino acid granules (2012)

The effect of malnutrition on survival in patients with decompensated liver cirrhosis has not been well defined. Nutritional intervention with branched-chain amino acid (BCAA) can increase serum albumin concentration in patients with decompensated cirrhosis but its effects on survival are unclear. The BCAA to tyrosine ratio (BTR) is a surrogate marker (the normal range of BTR is between 4.41 and 10.05, and a Fischer's ratio of 1.8 corresponds to a BTR of 3.5) in patients with decompensated liver cirrhosis, and BCAA inhibits hepatic carcinogenesis in patients with compensated cirrhosis. This review discusses data regarding the effect of early administration of BCAA granules based on the ratio of BCAA to BTR on prognosis in patients with cirrhosis.
The variable and conserved interfaces of modeled olfactory receptor proteins (1999)

The accumulation of hundreds of olfactory receptor (OR) sequences, along with the recent availability of detailed models of other G-protein-coupled receptors, allows us to analyze the OR amino acid variability patterns in a structural context. A Fourier analysis of 197 multiply aligned olfactory receptor sequences showed an alpha-helical periodicity in the variability profile. This was particularly pronounced in the more variable transmembranal segments 3, 4, and 5. Rhodopsin-based homology modeling demonstrated that the inferred variable helical faces largely point to the interior of the receptor barrel. We propose that a set of 17 hypervariable residues, which point to the barrel interior and are more extracellularly disposed, constitute the odorant complementarity determining regions. While 12 of these residues coincide with established ligand-binding contact positions in other G-protein-coupled receptors, the rest are suggested to form an olfactory-unique aspect of the binding pocket. Highly conserved olfactory receptor-specific sequence motifs, found in the second and third intracellular loops, may comprise the G-protein recognition epitope. The prediction of olfactory receptor functional sites provides concrete suggestions of site-directed mutagenesis experiments for altering ligand and G-protein specificity.