gebhart/patrepeval huggingface dataset:
Role of Yeast Glutaredoxins as Glutathione S-transferases (2003)

The yeast Saccharomyces cerevisiae contains two glutaredoxins, encoded by GRX1 and GRX2, that are required for resistance to reactive oxygen species. We recently reported that Grx1 is active as a glutathione peroxidase and can directly reduce hydroperoxides (Collinson, E. J., Wheeler, G. L., Garrido, E. O., Avery, A. M., Avery, S. V., and Grant, C. M. (2002) J. Biol. Chem. 277, 16712-16717). We now show that Grx2 is also a general hydroperoxidase, and kinetic data indicate that both enzymes have a similar pattern of activity, which is highest with hydrogen peroxide, followed by cumene hydroperoxide and tert-butyl hydroperoxide. Furthermore, both Grx1 and Grx2 are shown be active as glutathione S-transferases (GSTs), and their activity with model substrates such as 1-chloro-2,4-dinitrobenzene is similar to their activity with hydroperoxides. Analysis of the Grx1 active site residues shows that Cys-27, but not Cys-30, is required for both the peroxidase and transferase activities, indicating that these reactions proceed via a monothiol mechanism. Deletion analysis shows that Grx1 and Grx2 have an overlapping function with yeast GSTs, encoded by GTT1 and GTT2, and are responsible for the majority of cellular GST activity. In addition, multiple mutants lacking GRX1, GRX2, GTT1, and GTT2 show increased sensitivity to stress conditions, including exposure to xenobiotics, heat, and oxidants. In summary, glutaredoxins are multifunctional enzymes with oxidoreductase, peroxidase, and GST activity, and are therefore ideally suited to detoxify the wide range of xenobiotics and oxidants that can be generated during diverse stress conditions.
Effect of the chemopreventive agents piroxicam and D,L-α-difluoromethylornithine on intermediate biomarkers of colon carcinogenesis (1992)

Our previous studies have shown that dietary piroxicam, a non-steroidal anti-inflammatory drug (NSAID), and D,L-alpha-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, act as potential chemopreventive agents in inhibiting azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. The present study was designed to determine the effect of these chemopreventive agents on intermediate biomarkers, namely colonic epithelial cell proliferation and levels of prostaglandins, which can be used as effective predictors of colon cancer. Starting at 6 weeks of age, groups of animals were fed the control diet and experimental diets containing piroxicam or DFMO. At 7 weeks of age, all animals, except the vehicle controls, were injected s.c. with AOM at a dose level of 15 mg/kg body wt/week for 4 weeks. Vehicle controls received an equal volume of normal saline. Groups of animals were then killed at the end of last AOM or saline injection (baseline) and at week 4, 16, 24 and 32 following the last AOM or saline treatment. Animals intended for cell proliferation study were injected with bromodeoxyuridine (BrdU) at a dose level of 20 mg/kg body wt 1 h prior to being killed. The rate of colonic cell proliferation at all time points was assessed immunohistochemically using anti-BrdU. The levels of colonic mucosal prostaglandins were estimated by radioimmunoassay. The results indicate that carcinogen treatment increased the colonic cell proliferation measured as the crypt labeling index in proximal and distal colons and the concentrations of colonic prostaglandin E2 (PGE2) and 6-keto PGF1 alpha. The data demonstrate that DFMO significantly inhibited the AOM-induced labeling index in the distal and proximal colon at all time points, whereas piroxicam slightly decreased the labeling index. On the other hand, piroxicam exerted a pronounced inhibitory effect on the levels of both PGE2 and 6-keto PGF1 alpha. DFMO suppressed the colonic PGE2 levels to a lesser degree than piroxicam. The results demonstrate that DFMO, an inhibitor of ODC, suppresses cell proliferation, whereas piroxicam, a NSAID, inhibits prostaglandins, and emphasize the need to develop agent-dependent intermediate biomarker(s) to validate the efficacy of chemopreventive agent(s) in colon carcinogenesis.
Retinal degeneration is rescued in transgenic rd mice by expression of the cGMP phosphodiesterase beta subunit. (1992)

The beta subunit of the cGMP phosphodiesterase (PDE) gene has been identified as the candidate gene for retinal degeneration in the rd mouse. To study the molecular mechanisms underlying degeneration and the potential for gene repair, we have expressed a functional bovine cGMP PDE beta subunit in transgenic rd mice. One transgenic mouse line showed complete photoreceptor rescue across the entire span of the retina. A second independently derived line showed partial rescue in which photoreceptors in the superior but not the inferior hemisphere of the retina were rescued. In the latter animals, intermediate stages of degeneration were observed in the transition zone between rescued and diseased photoreceptors. Pathologic changes in the retina ranged from vesiculation of the basalmost outer segment discs in otherwise structurally intact rod cells to photoreceptors with highly disorganized outer segments and intact inner segments. Totally or partially rescued retinas showed a corresponding restoration of cGMP PDE activity, whereas nonrescued retinas had minimal enzyme activity, characteristic of the rd phenotype. These transgenic animals provide models for studying the molecular basis of retinal degenerative disease and conclusively demonstrate that the phenotype of rd mice is produced by a defect in the beta subunit of cGMP PDE.
Update on treatment options for Lambert&ndash;Eaton myasthenic syndrome: focus on use of amifampridine (2011)

In Lambert-Eaton myasthenic syndrome (LEMS), antibodies against presynaptic voltage-gated calcium channels reduce the quantal release of acetylcholine, causing muscle weakness and autonomic dysfunction. More than half of the affected patients have associated small cell lung cancer, and thorough screening for an underlying malignancy is crucial. The mainstay of treatment for LEMS is symptomatic but immunotherapy is needed in more severely affected patients. Symptomatic therapies aim at increasing the concentration of acetylcholine at the muscle endplate. While acetylcholinesterase inhibitors were the first drugs to be used for the amelioration of symptoms, 3,4-diaminopyridine (3,4-DAP, amifampridine) has been shown to be more effective. 3,4-DAP blocks presynaptic potassium channels, thereby prolonging the action potential and increasing presynaptic calcium concentrations. This then results in increased quantal release of acetylcholine. The efficacy of 3,4-DAP for increasing muscle strength and resting compound muscle action potentials has been demonstrated by four placebo-controlled trials. Side effects are usually mild, and the most frequently reported are paresthesias. The most common serious adverse events are epileptic seizures. 3,4-DAP is currently the treatment of choice in patients with Lambert-Eaton myasthenic syndrome.
Deimination of membrane-bound myelin basic protein in multiple sclerosis exposes an immunodominant epitope (2006)

The degradation of myelin in the CNS is the hallmark of multiple sclerosis. Reduction in the net positive charge of myelin basic protein (MBP), through deimination, correlates strongly with disease severity and may mediate myelin instability and loss of compaction. Using Cys scanning, spin labeling, EPR spectroscopy, and site-specific proteolysis, we show that in the membrane-bound state the primary immunodominant epitope, V83-T92, of the less cationic recombinant murine MBP C8 mimic (rmC8) forms a more highly surface-exposed and shorter amphipathic alpha-helix than in the unmodified form, recombinant murine MBP C1 mimic (rmC1), analogous to the most cationic and abundant isomer of MBP in normal myelin. Moreover, cathepsin D digested lipid-associated rmC8 3-fold faster than rmC1, and cleavage at F86-F87 occurred more readily in rmC8 than rmC1. These findings suggest a mechanism for initial loss of myelin stability and the autoimmune pathogenesis of multiple sclerosis.
Catechol‐Based Biomimetic Functional Materials (2012)

Catechols are found in nature taking part in a remarkably broad scope of biochemical processes and functions. Though not exclusively, such versatility may be traced back to several properties uniquely found together in the o-dihydroxyaryl chemical function; namely, its ability to establish reversible equilibria at moderate redox potentials and pHs and to irreversibly cross-link through complex oxidation mechanisms; its excellent chelating properties, greatly exemplified by, but by no means exclusive, to the binding of Fe(3+); and the diverse modes of interaction of the vicinal hydroxyl groups with all kinds of surfaces of remarkably different chemical and physical nature. Thanks to this diversity, catechols can be found either as simple molecular systems, forming part of supramolacular structures, coordinated to different metal ions or as macromolecules mostly arising from polymerization mechanisms through covalent bonds. Such versatility has allowed catechols to participate in several natural processes and functions that range from the adhesive properties of marine organisms to the storage of some transition metal ions. As a result of such an astonishing range of functionalities, catechol-based systems have in recent years been subject to intense research, aimed at mimicking these natural systems in order to develop new functional materials and coatings. A comprehensive review of these studies is discussed in this paper.
Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab (2006)

A 22-year-old patient whose primary kidney disease was focal segmental glomerulosclerosis (FSGS) developed severe recurrence of proteinuria (up to 57 g/24 h) immediately after a haploidentic living donor kidney transplantation despite pre-operative plasmapheresis. The immunosuppressive treatment consisted of tacrolimus, mycophenolate mofetil, basiliximab and steroids. He underwent 10 plasmapheresis sessions in the first 3-week post-transplantation. In addition, he received 2 i.v. doses of rituximab (RTX) 600 mg (375 mg/m(2)) on days 7 and 15. Proteinuria decreased below nephrotic range at day 14 and serum creatinine returned progressively to normal values. A short course of oral ciclophosphamide (100 mg/j) was administrated between days 22 and 40 and three additional plasmapheresis sessions on days 34, 39 and 49. This strategy allowed obtaining sustained full remission of the nephrotic syndrome (NS) and excellent graft function, which persists over 2 years after transplantation. No notable adverse events related to RTX or plasmapheresis were observed. This case suggests that RTX associated with plasmapheresis may be an effective treatment of recurrent NS because of FSGS.
Cyclic polymers: Methods and strategies (2012)

Abstract Cyclic polymers have different physical properties compared to their linear counterparts of the same molecular weight. These different properties could have potential impact in the production of new and exciting polymer products. For industry to commercialize such materials, cyclic polymers need to be made on large scales, have controlled molecular weight distributions, and have versatile chemical composition. This highlight article describes many of the synthetic methods and strategies for obtaining highly pure cyclic polymers, and presents kinetic attributes for some of the processes. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012
Electrophoretic Evidence that Single-Stranded Regions of 1 or More Nucleotides Dramatically Increase the Flexibility of DNA (1994)

The influence of single-stranded nicks and gaps on the flexibility of DNA has been investigated by subjecting to gel electrophoresis sets of molecules containing single-stranded regions of defined position and length. The DNA molecules were produced by ligating together synthetic oligomers that contained either nicks or single-stranded gaps of 1-4 nucleotides; the oligomer repeat lengths were 20, 21, 22, 23, or 26 bp, in order to produce nicks or gaps that were either in- or out-of-phase with the helix repeat of DNA. Nick-containing DNA molecules displayed nearly normal electrophoretic behavior, with maximum reductions in gel mobility (41 degrees C; 12% polyacrylamide gels) of approximately 10% for 230-bp molecules containing 10 nicks. In contrast, molecules containing gaps of 2-4 nucleotides demonstrated dramatic reductions in mobility, approaching one-half of the values of their full-duplex counterparts; molecules containing 1-nucleotide gaps displayed intermediate behavior. The observed (relative) mobilities of molecules containing gaps of more than 1 nucleotide were remarkably insensitive to temperature and to the presence of magnesium ions in the electrophoresis buffer. The central conclusion of the current study is that single-stranded gaps represent points of swivel-like character, whereas nicks retain much of the rigid character of double-helical DNA.
Molecular Prognostic Profile of Egyptian HCC Cases Infected with Hepatitis C Virus (2012)

The identified genes could provide a panel of new diagnostic and prognostic aids for HCC.
Carbon nanotube–nanocrystal heterostructures fabricated by electrophoretic deposition (2008)

Alternating layer, carbon nanotubes-nanocrystal composite films, comprising multi-walled carbon nanotubes (MWCNTs) and iron oxide (Fe(3)O(4)) nanocrystals, have been fabricated via electrophoretic deposition (EPD) on stainless steel and gold substrates. Low field-high current and high field-low current EPD schemes were integrated to produce the composite films. The low field-high current EPD approach produced porous mats from an aqueous suspension of the MWCNTs, while the high field-low current EPD approach produced tightly packed nanocrystal films from a dispersion of the nanocrystals in hexane. Large electric fields applied during the nanocrystal EPD and strong van der Waals interactions among the nanocrystals facilitated the formation of tightly packed nanocrystal films atop the MWCNT mats to create CNT mat-nanocrystal film composites. The surface coverage and homogeneity of the nanocrystal films improved with repeated deposition of the nanocrystals on the same mat. The assembly of nanotube mats on top of the CNT mat-nanocrystal film composite confirmed the feasibility of multilayered CNT mat-nanocrystal film heterostructures suitable for a range of devices. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques were employed to characterize the surface coverage, homogeneity, and topology of these composite films.
Solvent Quality Changes the Structure of G8 PAMAM Dendrimer, a Disagreement with Some Experimental Interpretations (2006)

We have performed approximately 20-40 ns of molecular dynamics (MD) simulations for the generation 8 PAMAM dendrimer in explicit water under varying pH conditions to study the structure of the dendrimer (approximately 156,738 atoms at low pH). This is the first report of such a long MD simulation of a larger generation PAMAM dendrimer including the effect of salt and counterions with explicit water molecules. We find that changing the pH from a high value (approximately 12) to a low value (approximately 3) changes the radius of gyration from Rg = 37.8 to 43.1 A (increasing by 13%). We also find significant back-folding of the primary amines and a large amount of water penetration inside the polymer. The increase in size with decrease in pH is consistent with our earlier studies on G3-G6 and agrees with the Monte Carlo theory by Welch and Muthukumar of G8 (Macromolecules, 1998, 31, 5892) and the experiments on G5 and G8 PAMAM dendrimer by Topp et al. (Macromolecules, 1999, 32, 7232). However, these results disagree dramatically with the interpretations of SANS experiments of G8 PAMAM dendrimers by Nisato et al. (Macromolecules, 2000, 33, 4172) who observe no change in the size of the dendrimer with variations of solution pH and ionic strength. We assume that the disagreement might arise from neglecting nonspherical shape, penetration of water and ions into the core, and aggregation, all of which might depend on pH.
Characterization of the five novel Ly‐6 superfamily members encoded in the MHC, and detection of cells expressing their potential ligands (2006)

Lymphocyte Antigen 6 (Ly-6) superfamily members are cysteine-rich, generally GPI-anchored cell surface proteins, which have definite or putative immune related roles. There are 27 members of this family described so far in the human genome and 37 in the mouse. Five of them are clustered in the class III region of the human and mouse MHCs. Following computational analyses, we functionally characterized the encoded proteins by creating epitope-tagged fusion constructs to determine molecular weight, complex formation, subcellular localization, post-translational modifications and ligand binding. We found that all human and mouse proteins were glycosylated, and most could form part of larger complexes. Human and mouse Ly6G6c and Ly6G6d, and mouse Ly6g6e were found to be GPI-anchored cell surface proteins, highly expressed at the leading edges of cells, on filopodia, which are normally involved in cell adhesion and migration. However, analysis of Ly6G5c and Ly6G5b indicated that they are potentially secreted proteins. Our results indicate that there are two subclusters of related Ly-6 proteins in this region of the MHC, with Ly6G6c, Ly6G6d, and Ly6G6e forming one and Ly6G5c and Ly6G5b forming another. In addition, by FACS analysis we have found that the potential ligands for human LY6G6C, LY6G6D, and LY6G5C are expressed on K562 cells, an undifferentiated megakaryocyte cell line, indicating a potential role in hematopoietic cell differentiation. This characterization of the five MHC class III region Ly-6 family members is of great relevance, as they represent 18% of the human Ly-6 protein family and 50% of the secreted ones.
Gestational and neonatal factors in the etiology of schizophrenia (1993)

This study evaluates research on gestational and neonatal factors implicated as causes of schizophrenia. These include obstetrical complications (particularly gestational hypoxia), viral infections, autoimmune agents, developmental deficits, and maternal stress. Evidence strongly suggests that these factors are importantly connected to the onset of adult schizophrenia.
The influence of a heat and moisture exchanger (HME) on the respiratory symptoms after total laryngectomy (1991)

The influence of a heat and moisture exchanger (HME) on the respiratory symptoms after total laryngectomy was studied in 42 patients. A significant reduction was found in the mean daily frequency of sputum production, forced expectoration in order to clean the airway and stoma cleaning after use of the HME for 6 weeks. Symptoms of fatigue and malaise decreased significantly, while social contact improved. Patients using oesophageal speech or an electrolarynx benefited more than patients using a voice prosthesis. The findings indicate that respiratory problems after total laryngectomy can be reduced significantly with the use of a device with heat and moisture exchanging properties. In turn, reduction of respiratory symptoms results in an improved quality of life.
Operation Voltage Dependence of Memory Cell Characteristics in Fully Depleted Floating-Body Cell (2005)

A one-transistor memory cell on silicon-on-insulator, called floating-body cell (FBC), has been developed and demonstrated. Threshold voltage difference between the "0"-state and the "1"-state, which is a key parameter for realizing a large-scale memory by FBCs, is measured and analyzed using a 96 kb array diagnostic monitor (ADM). A function test of the ADM yielded a fail-bit probability of 0.002%. A new metric relating to the fail-bit probability, that is, the ratio of the threshold voltage difference over the total threshold voltage variation, is introduced and applied to the measurement results. Read current distributions are also evaluated for various operation voltages. This paper also investigates substrate bias dependence of the threshold voltage unique to fully-depleted devices. Channel impurity and substrate impurity concentration dependence of the threshold voltage are analyzed based on experimental data and device simulation.
Identification of c-myc promoter-binding protein and X-box binding protein 1 as interleukin-6 target genes in human multiple myeloma cells. (1999)

Interleukin-6 (IL-6) is implicated in the in vivo proliferation of malignant plasma cells in multiple myeloma. To define the molecular basis of the IL-6-induced mitogenic response in myeloma cells, we applied STAR (subtractive transcriptional amplification of mRNA), a new differential expression analysis technology, to isolate mRNAs preferentially expressed in IL-6-treated versus untreated cultures of the factor-responsive myeloma cell line U266. From the resulting collection of STAR clones, sequence information was obtained for a total of 72 distinct transcripts. Of these, 29 were found to correspond to known genes, 22 matched expressed sequence tags in public databases and 21 showed no sequence similarity to any existing entries. Among the known genes uncovered in the screen were those encoding proteins that function in cell division, cell signalling and gene/protein expression. Northern blot analysis documented that two transcription factor genes chosen for further study, c-myc promoter-binding protein (MBP-1) and X-box binding protein 1 (XBP-1), were up-regulated in U266 cells about 3-fold relative to the cell cycle-dependent beta-actin gene 12 h after IL-6 treatment. Both genes were also similarly up-regulated by IL-6 in factor-dependent ANBL-6 myeloma cells. These results indicate that MBP-1 and XBP-1 are IL-6 genes in myeloma cells; as such, they may play a role in IL-6-mediated growth control in multiple myeloma.
Targeted Disruption of the Mouse Estrogen Sulfotransferase Gene Reveals a Role of Estrogen Metabolism in Intracrine and Paracrine Estrogen Regulation (2001)

Elicitation of biological responses by estrogen in target tissues requires the presence of ER as well as receptor-active ligand in the local microenvironment. Though much attention has been devoted to the study of the receptor in estrogen target tissues, the concept is emerging that tissue estrogen sensitivity may also be regulated by ligand availability through metabolic transformation in situ. Here, we show that targeted disruption, in the mouse, of an estrogen metabolic enzyme, estrogen sulfotransferase (EST), causes structural and functional lesions in the male reproductive system. EST catalyzes the sulfoconjugation and inactivation of estrogen and is expressed abundantly in testicular Leydig cells. Although knockout males were fertile and phenotypically normal initially, they developed age-dependent Leydig cell hypertrophy/hyperplasia and seminiferous tubule damage. Development of these lesions in the testis could be recapitulated by exogenous E2 administration in younger knockout mice, suggesting that they arose in older knockout mice from chronic estrogen stimulation. Older knockout mice were also found to have reduced testis and epididymis weights but increased seminal vesicle/coagulating gland weight because of tissue swelling. Furthermore, total and forward sperm motility of older knockout mice was reduced by 60% and 80%, respectively, and these mice produced smaller litters compared with age-matched wild-type males. These findings establish a role for EST in the male reproductive system and indicate that intracrine and paracrine estrogen activity can be modulated by a ligand transformation enzyme under a physiological setting. Thus, inhibition of estrogen metabolic enzymes by environmental chemicals, as has been demonstrated recently for the human EST, may constitute a novel mechanism of endocrine disruption in vivo.