gebhart/patrepeval huggingface dataset:
The regulation of poly-β-hydroxybutyrate metabolism in Azotobacter beijerinckii (1973)

1. The enzymes beta-ketothiolase, acetoacetyl-CoA reductase, acetoacetate-succinate CoA-transferase (;thiophorase') and d(-)-3-hydroxybutyrate dehydrogenase have been partially purified from crude extracts of glucose-grown nitrogen-fixing batch cultures of Azotobacter beijerinckii. The condensation of acetyl-CoA to acetoacetyl-CoA catalysed by beta-ketothiolase is inhibited by CoASH, and the reverse reaction is inhibited by acetoacetyl-CoA. Acetoacetyl-CoA reductase has K(m) for acetoacetyl-CoA of 1.8mum and is inhibited by acetoacetyl-CoA above 10mum. The enzyme utilizes either NADH or NADPH as electron donor. The second enzyme of poly-beta-hydroxybutyrate degradation, d(-)-3-hydroxybutyrate dehydrogenase, is NAD(+)-specific and is inhibited by NADH, pyruvate and alpha-oxoglutarate. CoA transferase is inhibited by acetoacetate, the product of hydroxybutyrate oxidation. In continuous cultures poly-beta-hydroxybutyrate biosynthesis ceased on relaxation of oxygen-limitation and the rates in situ of oxygen consumption and carbon dioxide evolution of such cultures increased without a concomitant increase in glucose uptake. 2. On the basis of these and other findings a cyclic mechanism for the biosynthesis and degradation of poly-beta-hydroxybutyrate is proposed, together with a regulatory scheme suggesting that poly-beta-hydroxybutyrate metabolism is controlled by the redox state of the cell and the availability of CoASH, pyruvate and alpha-oxoglutarate. beta-Ketothiolase plays a key role in the regulatory process. Similarities to the pathways of poly-beta-hydroxybutyrate biosynthesis and degradation in Hydrogenomonas are discussed.
RAGE Axis (2004)

Receptor for AGE (RAGE) is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. Engagement of RAGE by its signal transduction ligands evokes inflammatory cell infiltration and activation in the vessel wall. In diabetes, when fueled by oxidant stress, hyperglycemia, and superimposed stresses such as hyperlipidemia or acute balloon/endothelial denuding arterial injury, the ligand-RAGE axis amplifies vascular stress and accelerates atherosclerosis and neointimal expansion. In this brief synopsis, we review the use of rodent models to test these concepts. Taken together, our findings support the premise that RAGE is an amplification step in vascular inflammation and acceleration of atherosclerosis. Future studies must rigorously test the potential impact of RAGE blockade in human subjects; such trials are on the horizon.
Dendritic cells genetically engineered to simultaneously express endogenous tumor antigen and granulocyte macrophage colony-stimulating factor elicit potent therapeutic antitumor immunity. (2002)

Recently, several studies have shown that vaccine therapy using dendritic cells (DCs) genetically engineered to express a surrogate tumor antigen can effectively induce antitumor immunity. In this study, murine bone marrow DCs were adenovirally transduced with murine endogenous tumor antigen gp70 expressed in CT26 cells and granulocyte macrophage colony-stimulating factor (GM-CSF), and we examined whether antigen-specific CTL responses and therapeutic immunity could be induced in mice immunized with those genetically modified DCs. The cytotoxic activity against CT26 in mice immunized with gp70-transduced DCs was significantly higher than that in control (P < 0.01) and was enhanced by GM-CSF-cotransduction (P < 0.001). GM-CSF gene transfer into DCs expressing tumor-associated antigen enhances CC chemokine receptor 7 expression on DCs, leading to improved migratory capacity of DCs to draining lymph nodes. Consequently, an effective antitumor immune response would be induced. Vaccination using gp70-transduced DCs provided remarkable therapeutic efficacy in s.c. models. Moreover, it could be sufficiently augmented by GM-CSF-cotransduction of DCs. These results support that vaccination therapy using DCs simultaneously transduced with tumor-associated antigen can elicit potent CTL response, and GM-CSF-cotransduction of DCs could optimize therapeutic response. Further investigation is needed to optimize this vaccine therapy to achieve the obvious benefit in clinical application.
Survival of Bull Spermatozoa Seeded and Frozen at Different Rates in Egg Yolk-Tris and Whole Milk Extenders (1993)

Six factorially arranged experiments were designed to study effects of seeding, freezing, and thawing rates in whole milk and egg yolk-Tris extenders commonly used for commercial cryopreservation of bull sperm. In these extenders, semen normally is supercooled to -13 or -14 degrees C unless the sperm are seeded. When sperm were supercooled or seeded, either mechanically or with immobilized silver iodide, and frozen to -196 degrees C, the postthaw percentages of motile sperm were 59, 57, and 64%, respectively. Freezing rates of -15, -25, and -35 degrees C/min gave similar sperm survival rates and were superior to -5 degrees C/min. For milk, the critical freezing temperature extended to -75 degrees C before transfer to liquid nitrogen gave good results. For egg yolk-Tris extender, transfer to liquid nitrogen was less critical once -50 degrees C had been attained. Thawing of sperm in water baths at 25 and 45 degrees C gave similar results, and both temperatures were superior to 5 degrees C. The postthaw percentage of motile sperm in egg yolk-Tris was equal or superior to that of sperm frozen in milk. A freezing rate of -15 degrees C/min to -100 degrees C and thawing at 25 degrees C consistently gave good results.
Crystallization and crystallographic investigations of ribonucleotide reductase protein R1 from Escherichia coli (1993)

Crystals of Escherichia coli ribonucleotide reductase protein R1 have been grown in complex with a synthetic peptide corresponding to the carboxyl end of protein R2. Good quality crystals could only be obtained after improvement of the purification protocol and are of the space group R32 with hexagonal cell axes a = b = 226 A and c = 341 A. They contain 3 subunits per asymmetric unit and diffract to 2.5 A resolution in synchrotron radiation. A multiple isomorphous replacement map at 5.5A, improved by solvent flattening, shows that the dimeric molecules are elongated, about 110 A long. The dimer is thin in the middle around the molecular two-fold axis. The subunit is shaped like a bowl, probably with the active site in its center.
Aquatic Biofouling Prevention by Electrically Charged Nanocomposite Polymer Thin Film Membranes (2013)

Electrically conductive polymer-nanocomposite (ECPNC) tight nanofiltration (NF) thin film membranes were demonstrated to have biofilm-preventing capabilities under extreme bacteria and organic material loadings. A simple route to the creation and application of these polyamide-carbon nanotube thin films is also reported. These thin films were characterized with SEM and TEM as well as FTIR to demonstrate that the carbon nanotubes are embedded within the polyamide and form ester bonds with trimesoyl chloride, one of the monomers of polyamide. These polymer nanocomposite thin film materials boast high electrical conductivity (∼400 S/m), good NaCl rejection (>95%), and high water permeability. To demonstrate these membranes' biofouling capabilities, we designed a cross-flow water filtration vessel with insulated electrical leads connecting the ECPNC membranes to an arbitrary waveform generator. In all experiments, conducted in highly bacterially contaminated LB media, flux tests were run until fluxes decreased by 45 ± 3% over initial flux. Biofilm-induced, nonreversible flux decline was observed in all control experiments and a cross-flow rinse with the feed solution failed to induce flux recovery. In contrast, flux decrease for the ECPNC membranes with an electric potential applied to their surface was only caused by deposition of bacteria rather than bacterial attachment, and flux was fully recoverable following a short rinse with the feed solution and no added cleaning agents. The prevention of biofilm formation on the ECPNC membranes was a long-term effect, did not decrease with use, and was highly reproducible.
bcl-2 inhibits death of central neural cells induced by multiple agents. (1993)

The protooncogene bcl-2, which has been implicated in B-cell lymphoma development, inhibits apoptosis due to growth factor withdrawal in some, but not all, hematopoietic cells. Recently we found that bcl-2 also inhibits apoptosis in PC12 pheochromocytoma cells. We now report that bcl-2 inhibits the death of a central neural cell line due to serum and growth factor withdrawal, the calcium ionophore A23187, glucose withdrawal, membrane peroxidation, and, in some cases, free radical-induced damage. This broad range of protective effects of BCL-2 protein suggests that BCL-2 may interact with a central step in neural cell death. Measurements of intracellular free calcium suggest that BCL-2 alters the transduction of neural death signals at a point distal to the rise in intracellular free calcium.
PBX3 and MEIS1 Cooperate in Hematopoietic Cells to Drive Acute Myeloid Leukemias Characterized by a Core Transcriptome of the MLL -Rearranged Disease (2016)

Overexpression of HOXA/MEIS1/PBX3 homeobox genes is the hallmark of mixed lineage leukemia (MLL)-rearranged acute myeloid leukemia (AML). HOXA9 and MEIS1 are considered to be the most critical targets of MLL fusions and their coexpression rapidly induces AML. MEIS1 and PBX3 are not individually able to transform cells and were therefore hypothesized to function as cofactors of HOXA9. However, in this study, we demonstrate that coexpression of PBX3 and MEIS1 (PBX3/MEIS1), without ectopic expression of a HOX gene, is sufficient for transformation of normal mouse hematopoietic stem/progenitor cells in vitro. Moreover, PBX3/MEIS1 overexpression also caused AML in vivo, with a leukemic latency similar to that caused by forced expression of MLL-AF9, the most common form of MLL fusions. Furthermore, gene expression profiling of hematopoietic cells demonstrated that PBX3/MEIS1 overexpression, but not HOXA9/MEIS1, HOXA9/PBX3, or HOXA9 overexpression, recapitulated the MLL-fusion-mediated core transcriptome, particularly upregulation of the endogenous Hoxa genes. Disruption of the binding between MEIS1 and PBX3 diminished PBX3/MEIS1-mediated cell transformation and HOX gene upregulation. Collectively, our studies strongly implicate the PBX3/MEIS1 interaction as a driver of cell transformation and leukemogenesis, and suggest that this axis may play a critical role in the regulation of the core transcriptional programs activated in MLL-rearranged and HOX-overexpressing AML. Therefore, targeting the MEIS1/PBX3 interaction may represent a promising therapeutic strategy to treat these AML subtypes.
Brain damages in ketamine addicts as revealed by magnetic resonance imaging (2013)

Ketamine, a known antagonist of N-methyl-D-aspartic (NMDA) glutamate receptors, had been used as an anesthetic particularly for pediatric or for cardiac patients. Unfortunately, ketamine has become an abusive drug in many parts of the world while chronic and prolonged usage led to damages of many organs including the brain. However, no studies on possible damages in the brains induced by chronic ketamine abuse have been documented in the human via neuroimaging. This paper described for the first time via employing magnetic resonance imaging (MRI) the changes in ketamine addicts of 0.5-12 years and illustrated the possible brain regions susceptible to ketamine abuse. Twenty-one ketamine addicts were recruited and the results showed that the lesions in the brains of ketamine addicts were located in many regions which appeared 2-4 years after ketamine addiction. Cortical atrophy was usually evident in the frontal, parietal or occipital cortices of addicts. Such study confirmed that many brain regions in the human were susceptible to chronic ketamine injury and presented a diffuse effect of ketamine on the brain which might differ from other central nervous system (CNS) drugs, such as cocaine, heroin, and methamphetamine.
Apoptosis regulating genes in prostate cancer (review). (1998)

Prostatic adenocarcinoma is emerging as a major cause of morbidity and mortality in the male population in the western world. Programmed cell death (apoptosis) in the prostate is activated by hormone ablation and is under the control of several regulating genes including the tumour suppressor gene p53 and the proto-oncogene bcl-2. Bcl-2 belongs to a rapidly expanding family of genes which form two functionally antagonistic groups controlling cell death and survival. Apoptosis regulating genes appear to play an important role in the development and progression of prostatic adenocarcinoma and offer a potential target for future therapeutic strategies.
Movement‐related frequency modulation of beta oscillatory activity in the human subthalamic nucleus (2005)

Event-related changes of brain electrical rhythms are typically analysed as amplitude modulations of local field potential (LFP) oscillations, like radio amplitude modulation broadcasting. In telecommunications, frequency modulation (FM) is less susceptible to interference than amplitude modulation (AM) and is therefore preferred for high-fidelity transmissions. Here we hypothesized that LFP rhythms detected from deep brain stimulation (DBS) electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease could represent movement-related activity not only in AM but also in FM. By combining adaptive autoregressive identification with spectral power decomposition, we were able to show that FM of low-beta (13-20 Hz) and high-beta (20-35 Hz) rhythms significantly contributes to the involvement of the human STN in movement preparation, execution and recovery, and that the FM patterns are regulated by the dopamine levels in the system. Movement-related FM of beta oscillatory activity in the human subthalamic nucleus therefore provides a novel informational domain for rhythm-based pathophysiological models of cortico-basal ganglia processing.
Everolimus-eluting bioabsorbable stent – Abbot Vascular programme (2009)

Overview of the stent. (B) Magnified image of the stent. (C) Stent struts imaged by optical coherence tomography have a “black box” appearance. The stent strut thickness is 150 μm. (D and E) Multi-slice computed tomography delineates easily the contours of the stented vessel as the stent structures are not radio-opaque. The radio-opaque markers embedded at the stent extremities (white arrows) appear much larger than they really are because of a “blooming effect” due to partial volume averaging typical of highly radio opaque objects imaged by MSCT4.
Structural Specificity of Polyamines and Polyamine Analogues in the Protection of DNA from Strand Breaks Induced by Reactive Oxygen Species (1998)

Reactive oxygen species are known to induce strand breaks and/or base modifications in DNA. DNA strand breaks are associated with many pathologies and programmed cell death. We have examined the ability of the polyamines and their analogues to protect phi X-174 plasmid DNA from strand breakage induced by a oxygen-radical generating system. Spermine and several unsymmetrically substituted polyamine analogues reduced the amount of strand breakage at a physiologically relevant concentration of 1 mM. However, putrescine, spermidine, N1-acetylspermine, N1-acetylspermidine and symmetrically alkylated polyamine analogues were not able to reduce strand breakage at the same concentration. Thus, the unsymmetrically alkylated polyamine analogues and natural spermine can protect DNA against strand breakage induced by Cu(II)/H2O2 generated ROS similar to other more classical antioxidants.
Context-Dependent Nature of Destabilizing Mutations on the Stability of FKBP12 (1998)

The context-dependent nature in which mutations affect protein stability was investigated using the FK506-binding protein, FKBP12. Thirty-four mutations were made at sites throughout the protein, including residues located in the hydrophobic core, the beta-sheet, and the solvent-exposed face of the alpha-helix. Urea-induced denaturation experiments were used to measure the change in stability of the mutants relative to that of the wild type (Delta DeltaGU-F). The results clearly show that the extent of destabilization, or stabilization, is highly context-dependent. Correlations were sought in order to link Delta DeltaGU-F to various structural parameters. The strongest correlation found was between Delta DeltaGU-F and N, the number of methyl(ene) groups within a 6 A radius of the group(s) deleted. For mutations of buried hydrophobic residues, a correlation coefficient of 0.73 (n = 16,where n is the number of points) was obtained. This increased to 0.81 (n = 24) on inclusion of mutations of partially buried hydrophobic residues. These data could be superimposed on data obtained for other proteins for which similarly detailed studies have been performed. Thus, the contribution to stability from hydrophobic side chains, independent of the extent to which a side chain is buried, can be estimated quantitatively using N. This correlation appears to be a general feature of all globular proteins. The effect on stability of mutating polar and charged residues in the alpha-helix and beta-sheet was also found to be highly context-dependent. Previous experimental and statistical studies have shown that specific side chains can stabilize the N-caps of alpha-helices in proteins. Substitutions of Ile56 to Thr and Asp at the N-cap of the alpha-helix of FKBP12, however, were found to be highly destabilizing. Thus, the intrinsic propensities of an amino acid for a particular element of secondary structure can easily be outweighed by tertiary packing factors. This study highlights the importance of packing density in determining the contribution of a residue to protein stability. This is the most important factor that should be taken into consideration in protein design.
A Five-Strain Probiotic Combination Reduces Pathogen Shedding and Alleviates Disease Signs in Pigs Challenged with Salmonella enterica Serovar Typhimurium (2007)

Salmonella spp. infection is a major cause of gastroenteritis, with many thousands of cases reported in the European Union every year. The use of probiotics offers the potential to improve this situation. Here, we investigate the effects of oral treatment of pigs with a defined lactic acid bacteria culture mixture on both clinical and microbiological signs of Salmonella enterica serovar Typhimurium infection. Fifteen weaned pigs blocked by sex and weight were administered control milk or a mixture of five probiotic strains as either a milk fermentate or milk suspension for a total of 30 days. The mixture consisted of two strains of Lactobacillus murinus and one strain each of Lactobacillus salivarius subsp. salivarius, Lactobacillus pentosus, and Pediococcus pentosaceous. Following probiotic administration for 6 days, animals were challenged orally with serovar Typhimurium; the health of the animals and the microbiological composition of their feces were monitored for 23 days postinfection. Animals treated with probiotic showed reduced incidence, severity, and duration of diarrhea. These animals also gained weight at a greater rate than control pigs administered skim milk. Mean fecal numbers of Salmonella were significantly reduced in probiotic-treated animals at 15 days postinfection (P = 0.01). The administered probiotic bacteria improved both the clinical and microbiological outcome of Salmonella infection. These strains offer significant benefit for use in the food industry and may have potential in human applications.
Rapid, Easy Cyanation of Aryl Bromides and Chlorides Using Nickel Salts in Conjunction with Microwave Promotion (2003)

We report here a fast, easy, and efficient method for the preparation of aryl nitriles from aryl bromides and chlorides. The methodology for aryl bromides involves the use of either Ni(CN)(2) or NaCN and NiBr(2). With aryl chlorides, a mix of NaCN and NiBr(2) is used and the reaction proceeds via the in situ formation of the corresponding aryl bromide. The reaction can be performed in air and is complete within 10 min.
Dynamics and folding of single two-stranded coiled-coil peptides studied by fluorescent energy transfer confocal microscopy (2000)

We report single-molecule measurements on the folding and unfolding conformational equilibrium distributions and dynamics of a disulfide crosslinked version of the two-stranded coiled coil from GCN4. The peptide has a fluorescent donor and acceptor at the N termini of its two chains and a Cys disulfide near its C terminus. Thus, folding brings the two N termini of the two chains close together, resulting in an enhancement of fluorescent resonant energy transfer. End-to-end distance distributions have thus been characterized under conditions where the peptide is nearly fully folded (0 M urea), unfolded (7.4 M urea), and in dynamic exchange between folded and unfolded states (3.0 M urea). The distributions have been compared for the peptide freely diffusing in solution and deposited onto aminopropyl silanized glass. As the urea concentration is increased, the mean end-to-end distance shifts to longer distances both in free solution and on the modified surface. The widths of these distributions indicate that the molecules are undergoing millisecond conformational fluctuations. Under all three conditions, these fluctuations gave nonexponential correlations on 1- to 100-ms time scale. A component of the correlation decay that was sensitive to the concentration of urea corresponded to that measured by bulk relaxation kinetics. The trajectories provided effective intramolecular diffusion coefficients as a function of the end-to-end distances for the folded and unfolded states. Single-molecule folding studies provide information concerning the distributions of conformational states in the folded, unfolded, and dynamically interconverting states.
Computational prediction of N-linked glycosylation incorporating structural properties and patterns (2012)

NGlycPred is freely available to non-commercial users as a web-based server at http://exon.niaid.nih.gov/nglycpred/.
Protection Against Oxidative Stress‐induced Neuronal Cell Death‐A Novel Role for RU486 (1997)

Free radicals and oxidative stress-induced neuronal cell death have been implicated in a variety of neurological disorders. Therefore, neuroprotection is of primary interest in basic and preclinical neuroscience. Here it is shown that RU486 (mifepristone), a potent antagonist of progesterone and glucocorticoid receptors, protects rat primary hippocampal neurons, clonal mouse hippocampal cells and organotypic hippocampal slice cultures against oxidative stress-induced neuronal cell death. 10(-5) M RU486 prevents intracellular peroxide accumulation and cell death induced by amyloid beta protein, hydrogen peroxide and glutamate, neurotoxins that have been implicated in certain neurodegenerative disorders, including Alzheimer's disease. RU486 has a significant protective effect that is independent of the presence and activation of glucocorticoid or progesterone receptors. The neuroprotective activity of this well-studied drug may have an impact on therapeutic interventions for neurodegenerative conditions which involve peroxidation processes, such as stroke and Alzheimer's disease.
Placebo‐controlled pilot trial testing dose titration and intravenous, intramuscular and subcutaneous routes for ketamine in depression (2016)

Antidepressant response occurred at a range of doses and at <0.5 mg/kg. The dose-titration approach is a practical method for optimizing the efficacy - side-effects trade-off on an individual patient basis. This pilot study provides preliminary evidence for SC injection as a practical, feasible and efficacious treatment approach.