gebhart/patrepeval huggingface dataset:
Subcellular Distribution of Glycolyltransferases in Rodent Liver and Their Significance in Special Reference to the Synthesis of N-Glycolylneuraminic Acid1 (1992)

The enzymic synthesis, transfer, and utilization of glycolyl-CoA (i.e. 2-hydroxyacetyl-CoA) have been studied in rat and mouse livers. On the one hand, these tissues contain the enzyme activities allowing the synthesis of glycolyl-CoA from fatty acids (palmitate omega-hydroxylase, omega-hydroxypalmitoyl-CoA synthetase, and mitochondrial beta-oxidation of omega-hydroxypalmitoyl-CoA) and 3-hydroxypyruvic acid (oxidation by intact mitochondria). On the other hand, three types of glycolyltransferase activities can be demonstrated in rodent livers, depending on either carnitine, glucosamine, or glucosamine-6-phosphate. The subcellular distributions of these glycolyltransferase activities are similar to those of the corresponding acetyltransferase counterparts. Concerning carnitine glycolytransferase, the activity is widely distributed in the subcellular fractions, pointing out its occurrence in most cell compartments. By contrast, the glucosamine and glucosamine-6-phosphate glycolytransferase activities were located preferentially in the microsomal fraction. The condensation between glycolyl-CoA and glucosamine (or glucosamine-6-phosphate) raises the interesting question of the nature and the role of the resulting glycolylglucosamine molecule, especially in an alternative N-glycolylneuraminic acid synthesis pathway.
Mucosal defences against Giardia (2003)

Giardia lamblia (syn. G. duodenalis or G. intestinalis), the causative agent of giardiasis, is one of the most common causes worldwide of intestinal infections in humans. Symptomatic infection is characterized by diarrhoea, epigastric pain, nausea, vomiting, and weight loss, yet many infections are asymptomatic. The protozoan, unicellular parasite resides in the lumen and attaches to the epithelium and overlying mucus layers but does not invade the mucosa and causes little or no mucosal inflammation. Giardiasis is normally transient, indicating the existence of effective host defences, although re-infections can occur, which may be related to differences in infecting parasites and/or incomplete immune protection. Mucosal defences against Giardia must act in the small intestinal lumen in the absence of induction by classical inflammatory mediators. Secretory IgA antibodies have a central role in anti-giardial defence. B cell-independent mechanisms also exist and can contribute to eradication of the parasite, although their identity and physiological importance are poorly understood currently. Possible candidates are nitric oxide, antimicrobial peptides such as Paneth cell alpha-defensins, and lactoferrin. Elucidation of the key anti-giardial effector mechanisms will be important for selecting the best adjuvants in the rational development of vaccination strategies against Giardia.
Cloning and sequencing of the Candida albicans C‐4 sterol methyl oxidase gene (ERG25) and expression of an ERG25 conditional lethal mutation in Saccharomyces cerevisiae (2000)

The ERG25 gene encoding the Candida albicans C-4 sterol methyl oxidase was cloned and sequenced by complementing a Saccharomyces cerevisiae erg25 mutant with a C. albicans genomic library. The Erg25p is comprised of 308 amino acids and shows 65 and 38% homology to the enzymes from S. cerevisiae and Homo sapiens, respectively. The protein contains three histidine clusters common to nonheme iron-binding enzymes and an endoplasmic reticulum retrieval signal as do the proteins from S. cerevisiae and humans. A temperature-sensitive (ts) conditional lethal mutation of the C. albicans ERG25 was isolated and expressed in S. cerevisiae. Sequence analysis of the ts mutant indicated an amino acid substitution within the region of the protein encompassed by the histidine clusters involved in iron binding. Results indicate that plasmid-borne conditional lethal mutants of target genes have potential use in the rescue of Candida mutations in genes that are essential for viability.
The Numerous Postulated Biological Manifestations of Interleukin-1 (1984)

Abstract Over the past 25 years there has been an ever-expanding interest in the mediators that control the immune response [98,133], One of these is produced by macrophages and was first called “lymphocyte activating factor” [49–51] but is now designated “interleukin-1” (IL-1) [118]. As the physical characteristics of IL-1 began to be described, it was noted that they were similar to those of endogenous pyrogen (EP) [128] [151] and leukocytic endogenous mediator (LEM) [85]. Since then, many of the biochemical changes that occur in the host during infection, inflammation, or neoplasia have been attributed to this unique family of monokines. In this review, the family of monokines that has similar physical and biological properties will be referred to as EP/LEM/IL-1. When only one biological activity was measured, the designation will be for that activity. It will be the purpose of this review to examine the evidence that suggests that EP/ LEM/IL-1 has numerous biological activites and to describe its chemical and biological properties, species specificity, and possible sites of action. Finally, I will attempt to address the issue of why there might be a closely related group of mediators with such a broad range of biological activities.
In vivostability and kinetics of absorption and disposition of 3' phosphopropyl amine oligonucleotides (1992)

Development of oligonucleotide derivatives as therapeutic agents requires an understanding of their pharmacokinetic behavior. The in vivo disposition and stability of a prototype of such compounds are reported here. The compound studied, a relatively G-rich 38 base 3' phosphopropyl amine oligonucleotide (TFO-1), was cleared from the circulation with a half-life of approximately 10 minutes, displaying distribution kinetics consistent with a two compartment model. TFO-1 was also readily absorbed into circulation from the peritoneal cavity. All tissues examined except brain accumulated the compound reaching concentrations calculated to be in the micromolar range. TFO-1 was found to be stable in circulation and in tissues in that a large fraction of intact material was detected 8 hours after injection, as assessed by gel electrophoresis. Approximately 20-30% of the injected dose was excreted in the urine over an 8 hour period. These results suggest that G-rich oligonucleotides, minimally modified at the 3' end, are relatively stable in vivo and have distribution kinetics favorable to use as therapeutic agents.
Effect of an Intrauterine Device on the Gene Expression Profile of the Endometrium (2006)

Our results reveal that a refractory endometrium in a fertile woman produced by an IUD is induced by preventing the normal transition to a receptive gene expression profile through effects on a specific subset or cluster of genes that impact on endometrial receptivity.
Oxygen concentration in milk of healthy and mastitic cows and implications of low oxygen tension for the killing ofStaphylococcus aureusby bovine neutrophils (1988)

The partial pressure of O2 in milk from normal cows and from cows with mastitis was measured and the concentrations of O2 calculated. Oxygen levels of milk from normal cows were similar to those in venous plasma, but inflammation of the mammary gland led to a dramatic drop in O2 concentration to less than 10% of control values. Intracellular survival of Staphylococcus aureus strain M60 in bovine neutrophils was greater under anaerobic than aerobic conditions. The implications of low O2 concentrations in milk from infected mammary glands for the bactericidal activity of bovine neutrophils is discussed.
Structure and distribution of the Notch protein in developing Drosophila. (1989)

Antibodies to Notch show that it is a stable, high-molecular-weight transmembrane glycoprotein, with epidermal growth factor (EGF)-like elements exposed on the cell surface. The protein is phosphorylated variably on serines of the cytoplasmic domain. Individual Notch polypeptide chains appear to be associated with one another by disulfide bonds, suggesting that homotypic interaction of these proteins is required for function. Immunocytochemistry has revealed striking features of Notch expression that might clarify its function: Cells of the ventral neurogenic ectoderm become conspicuously labeled with the protein prior to embryonic neurogenesis, and Notch appears to be associated with cells destined for both neural and epidermal lineages. High levels of Notch become restricted to neuroblasts as they delaminate from the embryonic ectoderm and are apposed to mesoderm. Mesodermal cells express Notch also, suggesting a possible involvement in neurogenesis, or an unknown role in mesoderm differentiation. In larvae and pupae, a correlation of expression and neuroblast mitotic activity is seen for many cells. Notch produced by a dividing neuroblast may persist on derivative cells, including terminally differentiated neurons and nerve processes. In the larval eye imaginal disk, strong Notch expression appears in the morphogenetic furrow, uniformly on cell surfaces as they cluster to form ommatidia. Expression persists on ommatidia after release from the furrow. These patterns suggest a role for Notch in position-dependent development in both initiation and maintenance of cell-surface interactions. In the eye and embryonic ectoderm, uniform expression on cells interacting to produce different developmental lineages from a single primordium suggests that Notch alone may not be sufficient to elaborate cell fates.
A Role for Brassinosteroids in Light-Dependent Development of Arabidopsis (1996)

Although steroid hormones are important for animal development, the physiological role of plant steroids is unknown. The Arabidopsis DET2 gene encodes a protein that shares significant sequence identity with mammalian steroid 5 alpha-reductases. A mutation of glutamate 204, which is absolutely required for the activity of human steroid reductase, abolishes the in vivo activity of DET2 and leads to defects in light-regulated development that can be ameliorated by application of a plant steroid, brassinolide. Thus, DET2 may encode a reductase in the brassinolide biosynthetic pathway, and brassinosteroids may constitute a distinct class of phytohormones with an important role in light-regulated development of higher plants.
Identification and chemical synthesis of a ribosomal protein antigenic determinant in systemic lupus erythematosus. (1986)

The characteristics of eukaryotic ribosomal proteins P0, P1, and P2 (P proteins) and their antigenic determinants were studied using the sera of patients with systemic lupus erythematosus (SLE). P0, P1, and P2 were isolated as a macromolecular complex by preparative isoelectric focusing and anion-exchange chromatography in the presence of 6 M urea. The apparent molecular size of the complex was 140 kDa as determined by gel filtration on a Sephadex G-200 column. P0 may, therefore, be the eukaryotic equivalent of Escherichia coli ribosomal protein L10. In addition, all three P proteins were detected in the postribosomal supernatant of HeLa cells, and P0 and P1 were found to be more acidic than their ribosome-bound counterparts. Partial proteolysis experiments revealed that SLE anti-P sera recognized one or both ends of the P2 equivalent protein from Artemia salina (eL12). Sixteen SLE sera containing antibodies to P0, P1, and P2 reacted with a carboxyl-terminal peptide 22 amino acids in length of eL12 and not with an amino-terminal peptide of 20 amino acids. Even though the carboxyl-terminal peptide completely inhibited the ability of the antiserum to react with all three proteins on an immunological blot, the same peptide produced only small decreases in binding of the SLE antibody to the native, nondenatured P proteins. These findings indicate that SLE anti-P antibodies react with a single sequential (linear) antigenic determinant on all three P proteins, but that additional antibodies recognize a conformational determinant(s).
Techniques Employed in Production of Traditional Vaccines Commonly Used by Military Forces: A Review (2019)

The most successful and effective preventive measure against infection from a particular disease is to get vaccinated. Traditional vaccines use a dead or a weakened pathogenic microbe or a toxin from a pathogen. The introduction of an attenuated or dead pathogen into a healthy individual generates an immune response. Vaccines aid in creating a memory of the antigenic specificity of disease in the individual, thus immunizing the individual against that particular disease for a long period. Therefore, getting vaccinated for a disease is the best measure one can take, especially for military forces. Due to the circumstantial juxtaposition of a soldier in harsh environments while serving his nation with little to no amenities, the threat of a biological agent increases significantly. Thus, the maintenance of hygiene and immunity is of utmost importance in the military to prevent any setback in the line of duty. Some vaccines do require booster doses to retain the memory of antigenic specificity. Various techniques have been developed or are under development to produce effective vaccines for several diseases. A key development in traditional vaccines is the reduction of booster doses required, as well as the reduction of side effects. Any technique used to produce vaccines has to ensure the provision of long-term immunity to the individual, no side effects on the individual due to the vaccine, no relapse or reversion of pathogenicity, and induction of an immune response at a low dosage. This article aims to highlight the progress and failures in the development of different types of traditional vaccines, along with the procedures and techniques used in traditional vaccine production.
Thyroid Cancer: A Lethal Endocrine Neoplasm (1991)

This conference focuses on the controversies about managing thyroid cancer, emphasizing the possibility that the treatment of patients with potentially fatal thyroid cancer may be improved. Although the mortality rate from thyroid cancer is low, it is the highest among cancers affecting the endocrine glands (excluding the ovary). Exposure to radiation during childhood in the 1930s and 1940s increased the incidence of but not the mortality from thyroid cancer, because these tumors are mainly papillary cancers developing in young adults. These rates may change as the exposed cohort ages. Risk factors that increase mortality include older patient age and the growth characteristics of the tumor at diagnosis, the presence of distant metastases, and cell type (for example, the tall-cell variants of papillary cancer, follicular cancer [to be distinguished from the more benign follicular variant of papillary cancer], medullary cancer, and anaplastic cancer). Local metastases in lymph nodes do not seem to increase the risk for death from papillary cancer, but they do increase the risk for death from follicular and medullary cancer. In the latter, mortality is decreased by the early detection and treatment of patients with the familial multiple endocrine neoplasia syndrome 2a. There are excellent tumor markers for differentiated cancer of the parafollicular and of the follicular cells (serum calcitonin and serum thyroglobulin levels, respectively). Measuring the calcitonin level allows early diagnosis of familial medullary cancer, whereas measuring the thyroglobulin level, although useful only after total thyroidectomy, allows early recognition of recurrence or metastases of papillary or follicular cancer. Initial surgery, protocols for follow-up, and the use of radioiodine for the ablation of any residual thyroid and the treatment of metastatic cancer are discussed. Because these tumors resist currently available chemotherapy regimens, possible ways to increase the effectiveness of radioiodine therapy are considered as are new approaches to treatment.
Adeno-Associated Virus Vector Genomes Persist as Episomal Chromatin in Primate Muscle (2008)

Recombinant adeno-associated virus (rAAV) vectors are capable of mediating long-term gene expression following administration to skeletal muscle. In rodent muscle, the vector genomes persist in the nucleus in concatemeric episomal forms. Here, we demonstrate with nonhuman primates that rAAV vectors integrate inefficiently into the chromosomes of myocytes and reside predominantly as episomal monomeric and concatemeric circles. The episomal rAAV genomes assimilate into chromatin with a typical nucleosomal pattern. The persistence of the vector genomes and gene expression for years in quiescent tissues suggests that a bona fide chromatin structure is important for episomal maintenance and transgene expression. These findings were obtained from primate muscles transduced with rAAV1 and rAAV8 vectors for up to 22 months after intramuscular delivery of 5 x 10(12) viral genomes/kg. Because of this unique context, our data, which provide important insight into in situ vector biology, are highly relevant from a clinical standpoint.
Surface‐modified nanoparticles as a new, versatile, and mechanically robust nonadhesive coating: Suppression of protein adsorption and bacterial adhesion (2008)

The synthesis of surface-modified silica nanoparticles, chemically grafted with acrylate and poly(ethylene glycol) (PEG) groups, and the ability of the resulting crosslinked coatings to inhibit protein adsorption and bacterial adhesion are explored. Water contact angles, nanoindentation, and atomic force microscopy were used to characterize the cross-linked coatings. Coatings showed a high degree of hydrophilicity combined with a remarkable hardness and stiffness in the dry state. Adsorption of the small protein lysozyme from buffer solution on coated silica wafers decreased significantly with increasing grafting density of the PEG groups on the nanoparticles and was completely inhibited at 0.6 chains nm(-2). Coatings significantly reduced adhesion of Staphylococcus epidermidis HBH 276 in a parallel plate flow chamber with respect to bare glass (>90%), whereas adhesion of Pseudomonas aeruginosa AK1 was only marginally affected by the presence of the coating (<15%). Passage of an air-bubble resulted in almost complete detachment (>93%) of both strains from coated glass, indicating that the adhesion strength between both bacterial strains and the coated surface was significantly reduced by the grafted PEG groups. These coatings thus provide a new method to prepare mechanically robust films with nonadhesive properties that will be extremely useful for the design of biocompatible surfaces in biomedical applications.
A Platelet-Inhibitor-Drug Trial in Coronary-Artery Bypass Operations (1982)

To prevent occlusion of aortocoronary-artery-bypass grafts, we conducted a prospective, randomized-double-blind trial comparing dipyridamole (instituted two days before operation) plus aspirin (added seven hours after operation) with placebo in 407 patients. Vein-graft angiography was performed in 360 patients (88 per cent) within six months of operation (median, eight days). Within one month of operation, 3 per cent of vein-graft distal anastomoses (10 of 351) were occluded in the treated patients, and 10 per cent (38 of 362) in the placebo group; the proportion of patients with one or more distal anastomoses occluded was 8 per cent (10 of 130) in the treated group and 21 per cent (27 of 130) in th placebo group. This benefit in graft patency persisted in each of over 50 subgroups. Early postoperative bleeding was similar in the two groups. In this trial dipyridamole and aspirin were effective in preventing graft occlusion early after operation.
Sponge's Molecular Diversity Through the Ambivalent Reactivity of 2-Aminoimidazole: A Universal Chemical Pathway to the Oroidin-Based Pyrrole-Imidazole Alkaloids and Their Palau'amine Congeners (2001)

The plausible biogenetic mechanism proposed in this communication clarifies the chemical pathway leading to over 60 polycyclic pyrrole-imidazole marine alkaloids isolated from more than 20 different species of various genera (Agelas, Hymeniacidon, Axinella, Acanthella, Cymbastella, Phakellia...) of sponges. The tautomerism and ambivalent reactivity of 2-aminoimidazole precursors provide a consistent chemical pathway explaining the intriguing formation of all the compounds of this class. The mechanistic proposal proposed here for the first time is unique in the sense that the chemical pathway is universal and therefore provides fertile intellectual ground for the study of the enzymatic mechanism involved in this system.
Quantification of isomers from a mixture of twelve heparin and heparan sulfate disaccharides using tandem mass spectrometry (2005)

Heparin/heparan sulfate-like glycosaminoglycans (HSGAGs) have been implicated in clinically relevant processes such as hemostasis, infection, development, and cancer progression, through their interactions with proteins. Electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MSn) were combined to identify and quantify 12 HSGAG disaccharides that can be generated by enzymatic depolymerization with heparin lyases. This technique includes free amine-containing disaccharides that had previously been observed in MSn but not quantified. Our methods use diagnostic product ions from MSn spectra of up to three isomeric disaccharides at once, and up to three sequential stages of MSn in tandem, for the quantitative analysis of the relative percentage of each of these isomers. The isomer quantification was validated using mock mixtures and showed acceptable accuracy and precision. These methods may be applied to the quantification of other isomers by MSn. While each of the 12 disaccharides alone had a linear response to an internal standard in the MS1 spectra, the individual response factors did not remain constant when the concentrations of the other 11 disaccharides in the mixtures fluctuated, due to competition for electrospray ionization. The absolute concentration of one fluctuating isomer was determined out of a constant mixture of the other disaccharides. The rapid, accurate, and sensitive quantification of all isomeric disaccharides may contribute to the eventual sequencing of longer saccharides by MSn, enabling the elucidation of the structure-function relationships of HSGAGs.
Efficient coupled transcription/translation from PCR template by a hollow-fiber membrane bioreactor (1999)

A novel bioreactor using a hollow-fiber membrane was developed for the coupled transcription/translation system using T7 RNA polymerase and Escherichia coli S30 extract. The large surface area per the reaction volume of the reactor assured rapid mass transfers of substrates into the reaction mixture and of wastes out from it across the membrane by their molecular diffusion. The flux was large enough to maintain nucleotide concentrations for more than 3 h, which increased the protein synthesis greatly. In addition, the T7 terminator sequence downstream from the reporter genes was found to increase the synthesized protein significantly, especially when the product of polymerase chain reaction (PCR) was used as a template. Implementation of this finding and use of the bioreactor developed multiplied the productivity of protein by the in vitro direct expression from PCR template.