gebhart/patrepeval huggingface dataset:
EndoS and EndoS2 hydrolyze Fc-glycans on therapeutic antibodies with different glycoform selectivity and can be used for rapid quantification of high-mannose glycans (2015)

Enzymes that affect glycoproteins of the human immune system, and thereby modulate defense responses, are abundant among bacterial pathogens. Two endoglycosidases from the human pathogen Streptococcus pyogenes, EndoS and EndoS2, have recently been shown to hydrolyze N-linked glycans of human immunoglobulin G. However, detailed characterization and comparison of the hydrolyzing activities have not been performed. In the present study, we set out to characterize the enzymes by comparing the activities of EndoS and EndoS2 on a selection of therapeutic monoclonal antibodies (mAbs), cetuximab, adalimumab, panitumumab and denosumab. By analyzing the glycans hydrolyzed by EndoS and EndoS2 from the antibodies using matrix-assisted laser desorption ionization time of flight, we found that both the enzymes cleaved complex glycans and that EndoS2 hydrolyzed hybrid and oligomannose structures to a greater extent compared with EndoS. A comparison of ultra-high-performance liquid chromatography (LC) profiles of the glycan pool of cetuximab hydrolyzed with EndoS and EndoS2 showed that EndoS2 hydrolyzed hybrid and oligomannose glycans, whereas these peaks were missing in the EndoS chromatogram. We utilized this difference in glycoform selectivity, in combination with the IdeS protease, and developed a LC separation method to quantify high mannose content in the Fc fragments of the selected mAbs. We conclude that EndoS and EndoS2 hydrolyze different glycoforms from the Fc-glycosylation site on therapeutic mAbs and that this can be used for rapid quantification of high mannose content.
Effect of UVB radiation on seed germination, seedling growth, photosynthetic pigments and biochemical responses of Pistum sativum (L.) (2015)

The study focuses on the effect Ultraviolet-B rays (UV-B) were studied how it affected on seed germination seedling growth, chlorophyll a and b contents, soluble phenols, anthocyanins, flavones contents, phenylal of pea (Pisum saivum). The seed germination percentage significantly suppressed by UV-irradiance. Both root and shoot growth of the seedlings were markedly reduced by enhanced UV-B radiation. UV-B irradiation substantially decreased both chlorophylls a and b and the total amount of chlorophyll a plus b compared to controls. However, chlorophyll a/b ratio was generally elevated. Remarkable accumulation of total soluble phenols occurred in response to UV-B radiation. The levels of anthocyanins and flavones in treatments over the controls as they provide a protective mechanism to UV-B radiations. In general, the growth and physiological responses to UV-B radiation were more pronounced at greater exposure period.
Use of an Exotic Carbon Source To Selectively Increase Metabolic Activity and Growth of Pseudomonas putida in Soil (1993)

Respiration and growth of Pseudomonas putida PpG7, containing catabolic plasmid NAH7, was determined in three agricultural field soils amended with the carbon source salicylate. The addition of salicylate to soil significantly increased the population of PpG7. However, there was a lack of relationship between microbial numbers and activity as determined by evolution of CO(2). In soils containing 30 to 1,500 mug of salicylate per g, metabolic activities of PpG7 peaked between 18 and 42 h and population densities increased approximately 10-to 10-fold. However, the metabolic activity of PpG7 rapidly declined after salicylate was utilized, whereas peak population densities were maintained for the duration of the experiments (5 to 7 days). Thus, elevated population densities of PpG7 were represented by inactive cells. Soil type had only minor effects on respiration rates or growth curves of PpG7 when amended with comparable concentrations of salicylate. Respiration and growth rates were optimal at concentrations between 300 and 1,000 mug of salicylate per g in the test soils. At 1,500 to 2,500 mug/g, respiration and growth of PpG7 were initially suppressed, but after a short lag time both attained levels similar to or greater than those resulting from the use of lower concentrations of salicylate. The culturing of PpG7 on a salicylate-amended medium to induce salicylate-degradative enzymes did not affect the lag time before utilization of salicylate in soil. Although PpG7 competed well with fungi for the substrate, suppression of fungal populations with cycloheximide resulted in significantly increased population densities of PpG7 in two of three soils amended with salicylate. The beneficial activities of bacteria in soil are discussed in relation to population density, population metabolic activity, and selective carbon source utilization.
ROLE OF CYTOKINES IN RHEUMATOID ARTHRITIS (1996)

Analysis of cytokine mRNA and protein in rheumatoid arthritis tissue revealed that many proinflammatory cytokines such as TNF alpha, IL-1, IL-6, GM-CSF, and chemokines such as IL-8 are abundant in all patients regardless of therapy. This is compensated to some degree by the increased production of anti-inflammatory cytokines such as IL-10 and TGF beta and cytokine inhibitors such as IL-1ra and soluble TNF-R. However, this upregulation in homeostatic regulatory mechanisms is not sufficient as these are unable to neutralize all the TNF alpha and IL-1 produced. In rheumatoid joint cell cultures that spontaneously produce IL-1, TNF alpha was the major dominant regulator of IL-1. Subsequently, other proinflammatory cytokines were also inhibited if TNF alpha was neutralized, leading to the new concept that the proinflammatory cytokines were linked in a network with TNF alpha at its apex. This led to the hypothesis that TNF alpha was of major importance in rheumatoid arthritis and was a therapeutic target. This hypothesis has been successfully tested in animal models, of, for example, collagen-induced arthritis, and these studies have provided the rationale for clinical trials of anti-TNF alpha therapy in patients with long-standing rheumatoid arthritis. Several clinical trials using a chimeric anti-TNF alpha antibody have shown marked clinical benefit, verifying the hypothesis that TNF alpha is of major importance in rheumatoid arthritis. Retreatment studies have also shown benefit in repeated relapses, indicating that the disease remains TNF alpha dependent. Overall these studies demonstrate that analysis of cytokine expression and regulation may yield effective therapeutic targets in inflammatory disease.
The Use of Monoclonal Antibody 44-3A6 in Cell Blocks in the Diagnosis of Lung Carcinoma, Carcinomas Metastatic to Lung and Pleura, and Pleural Malignant Mesothelioma (1991)

Monoclonal antibody (MoAb) 44-3A6 recognizes a glandular differentiation-associated antigen and has been used to identify exocrine differentiation in pulmonary carcinomas. The authors assessed its value in the diagnosis of lung carcinomas metastatic to lung/pleura and pleural malignant mesothelioma (MM), using cell blocks derived from cytologic specimens. Sixty-three primary lung carcinomas, 31 metastatic adenocarcinomas (ACs) (from breast, gastrointestinal tract, or genitourinary tract), and 36 MMs were immunostained with 44-3A6, Leu-M1, and anti-carcinoembryonic antigen (CEA). The results confirm the value of 44-3A6 in identifying ACs but do not allow distinction between those of pulmonary, breast, GIT, or ovarian mucinous derivation. Endometrial, ovarian serous, and renal ACs are essentially nonreactive, as are almost all MMs. The occurrence of one positive MM predicates caution in interpreting 44-3A6 positivity in isolation, but, judiciously used with other discriminating antibodies such as Leu-M1 and anti-CEA, 44-3A6 is of value in the differential diagnosis of ACs and MMs. Further, its applicability to cytologic specimens may obviate the need for more invasive diagnostic procedures and lead to rapid, accurate diagnosis.
Holographic methods in X-ray crystallography. III. First numerical results (1993)

The holographic method for the completion of crystal structures, described in paper II [Szöke (1993). Acta Cryst. A 49 , 853–866], is implemented numerically. The purpose of these modest calculations is to show that the holographic method can handle real crystallographic data in easy problems and to test various algorithms for its implementation. Both synthetic and experimental data are used and sources of error are systematically introduced. The numerical experiments support the theory presented in paper II and show that the holographic method may be a potentially viable alternative to conventional methods for the completion of crystal structures.
Determination of rat heart morphology and function in vivo in two models of cardiac hypertrophy by means of magnetic resonance imaging. (1991)

It has been shown that converting enzyme inhibitors (CEI) attenuate ventricular dilatation and hypertrophy after myocardial infarction. In most studies, CEI treatment was started when ventricular dilatation and hypertrophy were already well under way. Therefore, we studied the effects on ventricular dilatation and hypertrophy, when CEI treatment was started in the acute phase of myocardial infarction. Immediately after a sham-operation or myocardial infarction in rats (sham: n = 8; MI: n = 17), treatment with zofenopril, a novel ACE-inhibitor, was started and continued during 42 days (long-term treatment). In a second group of rats, zofenopril was administered only during the first 5 days after myocardial infarction (short-term treatment); these rats were not treated with zofenopril during the remaining period of 37 days (sham: n = 5; MI: n = 13). Untreated rats served as controls (sham: n = 9; MI: n = 24). The results from this study showed that long-term treatment with zofenopril caused a significant reduction of left ventricular cavity volume in rats with moderate-to-large infarctions, which was accompanied by a significant reduction in the ratio of total heart weight to body weight. However, short-term treatment with zofenopril did not significantly reduce ventricular volume or total heart weight. Finally, both long- and short-term treatment resulted in a small, but statistically significant, reduction of septal wall thickness in sham-operated and infarcted rats. We conclude that CEI therapy decreases ventricular dilatation and hypertrophy after myocardial infarction, only when treatment is continued during the chronic phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacological characterization of the metabotropic glutamate receptor inhibitingd‐[3H]‐aspartate output in rat striatum (1993)

The effects of several agonists of the metabotropic glutamate receptor (mGluR) were studied in adult rat striatal slices by measuring (i) KCl (30 m m )‐induced output of previously taken up d ‐[ 3 H]‐aspartate (Asp), (ii) forskolin (30 μ m )‐induced adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) accumulation and (iii) phophoinositide (PI) hydrolysis. K + ‐induced efflux of d ‐[ 3 H]‐Asp was inhibited by the following mGluR agonists: (1S,3S,4S)‐(carboxycyclopropyl)glycine ( l ‐CCG‐I), (1S,3 R )‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3 R ‐ACPD) and quisqualic acid (Quis). 2‐Amino‐4‐phosphonobutyrate ( l ‐AP4) was inactive up to 300 μ m . The maximal inhibition of d ‐[ 3 H]‐Asp output was 60 ± 8%. The EC 50 s of mGluR agonists were: 0.5 μ m for l ‐CCG‐I, 100 μ m for 1S,3 R ‐ACPD and 100 μ m for Quis. Forskolin‐induced cyclic AMP accumulation was also inhibited by mGluR agonists. The maximal inhibition was 50 ± 4% and was obtained at a concentration of 10 μ m for l ‐CCG‐I and 100 μ m for 1S,3 R ‐ACPD. The EC 50 s for this inhibition were: 0.9 μ m for l ‐CCG‐I and 20 μ m for 1S,3 R ‐ACPD. Quis (300 μ m ) inhibited cyclic AMP accumulation by approximately 20%. l ‐AP4 slightly potentiated cyclic AMP accumulation. PI hydrolysis was stimulated by mGluR agonists. The most potent compound was Quis (100 μ m ), which increased inositol phosphate formation up to 2.2 fold over control values. Its EC 50 was 15 μ m.l ‐CCG‐I and 1S,3 R ‐ACPD increased inositol phosphate formation by approximately 1.8 fold and their EC 50 values were 30 and 25 μ m , respectively. l ‐AP4 did not affect PI hydrolysis. In conclusion, mGluR agonists that reduce d ‐[ 3 H]‐Asp output have a pharmacological profile similar to that of mGluR agonists inhibiting cyclic AMP accumulation. l ‐CCG‐I appears to be a relatively selective agonist for the mGluR receptor which inhibits d ‐[ 3 H]‐Asp efflux and cyclic AMP accumulation, while Quis appears to act preferentially on the mGluR receptor linked to the metabolism of PIs.
Mouse immunoglobulin D: construction and characterization of a cloned delta chain cDNA. (1980)

TEPC 1017 is a BALB/c plasmacytoma that synthesizes IgD in large enough amounts to permit the isolation of mRNA for mouse delta chains. cDNA has been prepared from this mRNA, and an 880-base-pair fragment of it has been cloned by recombinant DNA techniques. The hybridization selection technique has been used to show that this cDNA clone specifically binds only mRNA that can be translated into immunoprecipitable delta chains. the sequence of a portion of this clone has been determined and, when translated, shows homology with the C delta 3 of a human myeloma protein. Using this cDNA clone as a probe, we have found that several different-sized delta RNAs are present in TEPC 1017 and in another IgD-secreting plasmacytoma, TEPC 1033.
Theory and Practice of Histological Techniques (1990)

Light Microscopy. Fixation and Fixatives. Tissue Processing, Microtomy and Paraffin Sections. Frozen and Related Sections. The Theory of Staining and It Practical Implications. The Haematoxylins and Eosin. Connective Tissue and Stains. Proteins and Nucleic Acids. Amyloid. Carbohydrates. Lipids. Pigments and Minerals. The Neuroendocrine System. Micro-Organisms. Bone. Techniques in Neuropathology. Cytoplasmic Granules, Organelles and Special Tissues. Enzyme Histochemistry. Enzyme Histochemistry: Diagnostic Applications. Immunofluorescent Techniques. Immunocytochemical Techniques. Immunocytochemistry in Diagnostic Tumour Pathology. In-Situ Hybridisation. Diagnostic Cytopathology, Specimen Collection and Preparation. Diagnostic Cytopathology, Cell Appearances. Resin Embedding Media. Electron Microscopy 1: Instrumentation and Image Formation. Electron Microscopy 2: Practical Procedures. Electron Microscopy 3: Diagnostic Applications. Quantitation in Histopathology. Safety in the Histopathology Laboratory. Audit in Histopathology. Museum and Other Demonstration Techniques.
Two Mammalian Longevity Assurance Gene (LAG1) Family Members, trh1 and trh4, Regulate Dihydroceramide Synthesis Using Different Fatty Acyl-CoA Donors (2003)

Overexpression of upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast longevity assurance gene (LAG1), selectively induces the synthesis of stearoyl-containing sphingolipids in mammalian cells (Venkataraman, K., Riebeling, C., Bodennec, J., Riezman, H., Allegood, J. C., Sullards, M. C., Merrill, A. H. Jr., and Futerman, A. H. (2002) J. Biol. Chem. 277, 35642-35649). Gene data base analysis subsequently revealed a new subfamily of proteins containing the Lag1p motif, previously characterized as translocating chain-associating membrane (TRAM) protein homologs (TRH). We now report that two additional members of this family regulate the synthesis of (dihydro)ceramides with specific fatty acid(s) when overexpressed in human embryonic kidney 293T cells. TRH1 or TRH4-overexpression elevated [3H](dihydro)ceramide synthesis from l-[3-3H]serine and the increase was not blocked by the (dihydro)ceramide synthase inhibitor, fumonisin B1 (FB1). Analysis of sphingolipids by liquid chromatography-electrospray tandem mass spectrometry revealed that TRH4 overexpression elevated mainly palmitic acid-containing sphingolipids whereas TRH1 overexpression increased mainly stearic acid and arachidic acid, which in both cases were further elevated upon incubation with FB1. A similar fatty acid specificity was obtained upon analysis of (dihydro)ceramide synthase activity in vitro using various fatty acyl-CoA substrates, although in a FB1-sensitive manner. Moreover, in homogenates from TRH4-overexpressing cells, sphinganine, rather than sphingosine was the preferred substrate, whereas no preference was seen in homogenates from TRH1-overexpressing cells. These findings lend support to our hypothesis (Venkataraman, K., and Futerman, A. H. (2002) FEBS Lett. 528, 3-4) that Lag1p family members regulate (dihydro)ceramide synthases responsible for production of sphingolipids containing different fatty acids.
Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function. (1997)

Catecholamines play a central role in the regulation of energy expenditure, in part by stimulating lipid mobilization through lipolysis in fat cells. The beta-2 adrenoceptor (BAR-2) is a major lipolytic receptor in human fat cells. To determine whether known polymorphisms in codons 16, 27, and 164 of this receptor play a role in obesity and subcutaneous adipocyte BAR-2 lipolytic function, we investigated a group of 140 women with a large variation in body fat mass. Only the polymorphisms in codons 16 and 27 were common in the study population. The Gln27Glu polymorphism was markedly associated with obesity with a relative risk for obesity of approximately 7 and an odds ratio of approximately 10. Homozygotes for Glu27 had an average fat mass excess of 20 kg and approximately 50% larger fat cells than controls. However, no significant association with changes in BAR-2 function was observed. The Arg16Gly polymorphism was associated with altered BAR-2 function with Gly16 carriers showing a fivefold increased agonist sensitivity and without any change in BAR-2 expression. However, it was not significantly linked with obesity. These findings suggest that genetic variability in the human BAR-2 gene could be of major importance for obesity, energy expenditure, and lipolytic BAR-2 function in adipose tissue, at least in women.
Phenotypic spectrum of patients with PLA2G6 mutation and PARK14 -linked parkinsonism (2010)

Although the clinical presentation of PLA2G6-associated neurodegeneration was reported to be homogeneous, our findings suggest patients with PLA2G6 mutation could show heterogeneous phenotype such as dystonia-parkinsonism, dementia, frontotemporal atrophy/hypoperfusion, with or without brain iron accumulation. Based on the clinical heterogeneity, the functional roles of PLA2G6 and the roles of PLA2G6 variants including single heterozygous mutations should be further elucidated in patients with atypical parkinsonism, dementia, or Parkinson disease. PLA2G6 mutations should be considered in patients with early-onset l-dopa-responsive parkinsonism and dementia with frontotemporal lobar atrophy.
Requirement of bic/microRNA-155 for Normal Immune Function (2007)

MicroRNAs are a class of small RNAs that are increasingly being recognized as important regulators of gene expression. Although hundreds of microRNAs are present in the mammalian genome, genetic studies addressing their physiological roles are at an early stage. We have shown that mice deficient for bic/microRNA-155 are immunodeficient and display increased lung airway remodeling. We demonstrate a requirement of bic/microRNA-155 for the function of B and T lymphocytes and dendritic cells. Transcriptome analysis of bic/microRNA-155-deficient CD4+ T cells identified a wide spectrum of microRNA-155-regulated genes, including cytokines, chemokines, and transcription factors. Our work suggests that bic/microRNA-155 plays a key role in the homeostasis and function of the immune system.
Electroosmotic enhancement of the binding of a neutral molecule to a transmembrane pore (2003)

The flux of solvent water coupled to the transit of ions through protein pores is considerable. The effect of this electroosmotic solvent flow on the binding of a neutral molecule [beta-cyclodextrin (betaCD)] to sites within the staphylococcal alpha-hemolysin pore was investigated. Mutant alpha-hemolysin pores were used to which betaCD can bind from either entrance and through which the direction of water flow can be controlled by choosing the charge selectivity of the pore and the polarity of the applied potential. The Kd values for betaCD for individual mutant pores varied by >100-fold with the applied potential over a range of -120 to +120 mV. In all cases, the signs of the changes in binding free energy and the influence of potential on the association and dissociation rate constants for betaCD were consistent with an electroosmotic effect.
Regiochemical control of the ring opening of 1,2-epoxides by means of chelating processes. 4. Synthesis and reactions of the cis- and trans-oxides derived from 3-[(benzyloxy)methyl]cyclohexene (1992)

The synthesis and nucleophilic addition reactions of diastereoisomeric title epoxides cis-7 and trans-8 were studied. While the ring-opening reactions of trans epoxide 8 are rationalized by means of steric, stereolectronic, and conformational arguments, the analogous reactions of cis epoxide 7 indicate the ability of this isomer to react through chelated intermediates when metal salt catalyst is used. In 7 chelation reaction conditions led to a significant increase of nucleophilic attack on the C-1 oxirane carbon; the lack of reversal of the regiochemistry of the ring opening on passing from nonchelating to chelating reaction conditions suggests that cis epoxide 7 reacts through its more stable conformation in both of the two different operating conditions.
IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasis (2010)

IL-23 is an important molecular driver of Th17 cells and has strong tumor-promoting proinflammatory activity postulated to occur via adaptive immunity. Conversely, more recently it has been reported that IL-17A elicits a protective inflammation that promotes the activation of tumor-specific CD8(+) T cells. Here we show the much broader impact of IL-23 in antagonizing antitumor immune responses primarily mediated by innate immunity. Furthermore, the majority of this impact was independent of IL-17A, which did not appear critical for many host responses to tumor initiation or metastases. IL-23-deficient mice were resistant to experimental tumor metastases in three models where host NK cells controlled disease. Immunotherapy with IL-2 was more effective in mice lacking IL-23, and again the protection afforded was NK cell mediated and independent of IL-17A. Further investigation revealed that loss of IL-23 promoted perforin and IFN-gamma antitumor effector function in both metastasis models examined. IL-23-deficiency also strikingly protected mice from tumor formation in two distinct mouse models of carcinogenesis where the dependence on host IL-12p40 and IL-17A was quite different. Notably, in the 3'-methylcholanthrene (MCA) induction of fibrosarcoma model, this protection was completely lost in the absence of NK cells. Overall, these data indicate the general role that IL-23 plays in suppressing natural or cytokine-induced innate immunity, promoting tumor development and metastases independently of IL-17A.
Induction of apoptosis in human retinoblastoma cells by topoisomerase inhibitors. (1998)

Topoisomerase inhibitors induce apoptosis in Y79 cells. This event is accompanied by a decrease in the expression of Bcl-2, a death antagonist, and an increase in that of Bax, a death agonist. A probable consequence of these modifications is the activation of ICE-like activity with degradation of poly-(adenosine diphosphate [ADP] ribose)-polymerase. Insulin-like growth factor-I exerts an antiapoptotic action in Y79 cells, and this function is most likely reduced by the overexpression of IGF-BP3 that is induced by drug treatment.