gebhart/patrepeval huggingface dataset:
Characterization of a Goα Mutant That Binds Xanthine Nucleotides (1997)

Several GTP binding proteins, including EF-Tu, Ypt1, rab-5, and FtsY, and adenylosuccinate synthetase have been reported to bind xanthine nucleotides when the conserved aspartate residue in the NKXD motif was changed to asparagine. However, the corresponding single Goalpha mutant protein (D273N) did not bind either xanthine nucleotides or guanine nucleotides. Interestingly, the introduction of a second mutation to generate the Goalpha subunit D273N/Q205L switched nucleotide binding specificity to xanthine nucleotide. The double mutant protein GoalphaD273N/Q205L (GoalphaX) bound xanthine triphosphate, but not guanine triphosphate. Recombinant GoalphaX (GoalphaD273N/Q205L) formed heterotrimers with betagamma complexes only in the presence of xanthine diphosphate (XDP), and the binding to betagamma was inhibited by xanthine triphosphate (XTP). Furthermore, as a result of binding to XTP, the GoalphaX protein underwent a conformational change similar to that of the activated wild-type Goalpha. In transfected COS-7 cells, we demonstrate that the interaction between GoalphaX and betagamma occurred only when cell membranes were permeabilized to allow the uptake of xanthine diphosphate. This is the first example of a switch in nucleotide binding specificity from guanine to xanthine nucleotides in a heterotrimeric G protein alpha subunit.
Brief Report: Induction of sustained remission in recurrent catastrophic antiphospholipid syndrome via inhibition of terminal complement with eculizumab (2012)

This first report of the use and clinical efficacy of eculizumab, an inhibitor of complement activation, in the treatment of CAPS demonstrates both the importance of complement (specifically, terminal complement components) in the pathogenesis of CAPS and the therapeutic benefit of complement inactivation.
Use of inert gas jets to measure the forces required for mechanical gene transfection (2012)

The results show that the number of cells transfected with the plasmid scales with the dynamic pressure of the jet. Our results show that mechanical methods have a very small window in which cells are permeabilized without injury (200 to 290 Pa). This simple apparatus helps define the forces needed for physical cell transfection methods.
Conduction velocity and refractory period of single motor nerve fibres in antecedent poliomyelitis. (1987)

The axonal conduction velocity and the axonal refractory period were determined using electromyographic techniques for 60 single motor units in 11 patients with antecedent poliomyelitis. The results were compared with previous observations in healthy subjects as well as subjects with motor neuron disease. In antecedent poliomyelitis there was a reduced proportion of nerve fibres with low conduction velocity as compared with the findings in healthy subjects. The mean value of the axonal conduction velocities in antecedent poliomyelitis (42.4 +/- 3.7 m/s, M +/- SD) was significantly higher (p less than 0.01) while in motor neuron disease the corresponding value (35.2 +/- 7.8 m/s) was significantly lower (p less than 0.005) than in healthy subjects (39.8 +/- 4.9 m/s). In antecedent poliomyelitis the conduction velocity and refractory period were related as in healthy subjects while abnormally long refractory periods were observed in motor neuron disease.
The organization of the Bacillus subtilis 168 chromosome region between the spoVA and serA genetic loci, based on sequence data (1993)

Summary Three different lambda phage clones with overlapping inserts of Bacillus subtilis DNA, which cover the region from spoIIAA to serA , have been isolated. The nucleotide sequence of their inserts, starting after spoVAF and ending at serA , has been determined. A contiguous sequence of 35354 bp was established, including previously analysed overlapping adjacent regions. Within the newly determined sequence 31 open reading frames (ORFs) with putative ribosome‐binding sites have been found. Nine of them correspond to previously sequenced and characterized genes: spoVAF, lysA, sipS, ribG, ribB, ribA, ribH, ribTD and dacB. Comparison of the amino acid sequences of the products encoded by the other ORFs to known proteins allowed putative functions to be assigned to seven of these ORFs. Among these are the following: (i) the ppiB gene, encoding a cytoplasmic peptidylprolyl isomerase; (ii) two pairs of signal‐transducers, one homologous to phoR–phoP of B. subtilis , encoding regulators of phosphatase biosynthesis, and the second to the fecI–fecR of Escherichia coli , which is responsible for the regulation of the citrate‐dependent iron (III) transport system; (iii) aroC and serA genes, involved in the biosynthesis of aromatic amino acids and serine, respectively, the function of which has beer: confirmed by constructing corresponding mutants with disrupted ORFs. The organization of putative operons has been postulated on the basis of the sequences of their transcription terminators, promoters and regulatory elements.
DNA damage is able to induce senescence in tumor cells in vitro and in vivo. (2002)

Often the use of cytotoxic drugs in cancer therapy results in stable disease rather than regression of the tumor, and this is typically seen as a failure of treatment. We now show that DNA damage is able to induce senescence in tumor cells expressing wild-type p53. We also show that cytotoxics are capable of inducing senescence in tumor tissue in vivo. Our results suggest that p53 and p21 play a central role in the onset of senescence, whereas p16(INK4a) function may be involved in maintaining senescence. Thus, like apoptosis, senescence appears to be a p53-induced cellular response to DNA damage and an important factor in determining treatment outcome.
Ocular Irritation: Microscopic Changes Occurring Over Time in the Rat with Surfactants of Known Irritancy (1998)

The pathology of surfactant-induced ocular irritation, especially in the context of accidental human exposures and animal tests used to assess a surfactant's potential ocular irritation, is not well understood. The purpose of this study was to characterize the microscopic changes in rats at 3 hr and on days 1, 2, 3, 4, 7, 14, and 35 following treatment with anionic, cationic, and nonionic surfactants of differing irritancy. The right eye of each rat was treated by placing 10 microliters of a surfactant directly on the cornea. Untreated left eyes served as the controls. At each time point, eyes and eyelids were macroscopically examined and collected for microscopic examination. Macroscopically, the differing levels of irritation were characterized by differences in incidence and magnitude of scores, reflecting involvement of the cornea, conjunctiva, and iris, as well as by the incidence of neovascularization and time to recovery. Microscopically, differences in the area and depth of injury paralleled the differences seen grossly and the relative irritancy of the various surfactants. All surfactants affected the corneal and conjunctival epithelium. All surfactants, except the slightly irritating anionic surfactant, caused corneal stromal changes, with this involvement being proportional to their overall level of irritation. Corneal endothelial cell effects principally occurred with only the severely irritating cationic surfactant. Over time, responses to surfactants of differing irritancy were qualitatively and quantitatively different, and these differences correlated with the extent of initial injury. Qualitative differences in response included presence of keratocyte regeneration, corneal neovascularization, and conjunctivalization of the corneal epithelium with all of the surfactants except the slight irritant. Quantitative differences in response occurred in the extent of epithelial regeneration, edema, and inflammation for surfactants of slight to severe irritancy, and with neovascularization, keratocyte regeneration, and conjunctivalization for surfactants of mild to severe irritancy. These results suggest that by defining initial area and depth of injury associated with an ocular irritant, it may be possible to predict the subsequent response and final outcome. Such an approach would be applicable to the development of mechanistically based in vitro assays.
Three-dimensional dynamic behaviour of the human knee joint under impact loading (1998)

The objective of this study is to determine the three-dimensional dynamic response of the human knee joint. A three-dimensional anatomical dynamic model was thus developed and consists of two body segments in contact (the femur and tibia) executing a general three-dimensional dynamic motion within the constraints of the different ligamentous structures. Each of the articular surfaces at the tibio-femoral joint was represented mathematically by a separate mathematical function. The joint ligaments were modelled as nonlinear elastic springs. The six-degrees-of-freedom joint motions were characterized by using six kinematic parameters, and ligamentous forces were expressed in terms of these six parameters. Knee response was studied by considering sudden external forcing pulse loads applied to the tibia. Model equations consist of nonlinear second-order ordinary differential equations coupled with nonlinear algebraic constraint conditions. Constraint equations were written to maintain at least one-point contact throughout motion; one- and two-point contact versions of the model were developed. This Differential-Algebraic Equations (DAE) system was solved by employing a DAE solver: the Differential/Algebraic System Solver (DASSL) developed at Lawrence Livermore National Laboratory. A solution representing the response of this three-dimensional dynamic system was thus obtained for the first time. Earlier attempts to determine the system's response were unsuccessful owing to the inherent numerical instabilities in the system and the limitations of the solution techniques. Under the conditions tested, evidence of "femoral roll back" on both medial and lateral tibial plateaus was not observed from the model predictions. In the range of 20 degrees to 66 degrees of knee flexion, the lateral tibial contact point moved posteriorly while the medial tibial contact point moved anteriorly. In the range of 66 degrees to 90 degrees of knee flexion, contact was maintained only on the medial side and the tibial contact point (on the medial side) continued to move anteriorly. It was further found that increasing pulse amplitude and/or duration caused a decrease in the magnitude of the tibio-femoral contact force at a given flexion angle. These results suggest that increasing load level caused a decrease in joint stiffness. The results of this study also show that the anterior fibres of the posterior cruciate and the medial collateral ligaments are the primary restraints for a posterior forcing pulse in the range of 20 degrees to 90 degrees of knee flexion; this explains why most isolated posterior cruciate ligament injuries and combined injuries to the posterior cruciate and the medial collateral result from a posterior impact on a flexed knee.
Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus (2003)

Disuse by bed rest, limb immobilization or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. This net bone loss increases the risk of fracture upon remobilization. Bone loss also occurs in hibernating ground squirrels, golden hamsters, and little brown bats by arresting bone formation and accelerating bone resorption. There is some histological evidence to suggest that black bears Ursus americanus do not lose bone mass during hibernation (i.e. disuse). There is also evidence suggesting that muscle mass and strength are preserved in black bears during hibernation. The question of whether bears can prevent bone loss during hibernation has not been conclusively answered. The goal of the current study was to further assess bone metabolism in hibernating black bears. Using the same serum markers of bone remodeling used to evaluate human patients with osteoporosis, we assayed serum from five black bears, collected every 10 days over a 196-day period, for bone resorption and formation markers. Here we show that bone resorption remains elevated over the entire hibernation period compared to the pre-hibernation period, but osteoblastic bone formation is not impaired by hibernation and is rapidly accelerated during remobilization following hibernation.
Widespread AAV1- and AAV2-mediated transgene expression in the nonhuman primate brain: implications for Huntington's disease (2016)

Huntington's disease (HD) is caused by a toxic gain-of-function associated with the expression of the mutant huntingtin (htt) protein. Therefore, the use of RNA interference to inhibit Htt expression could represent a disease-modifying therapy. The potential of two recombinant adeno-associated viral vectors (AAV), AAV1 and AAV2, to transduce the cortico-striatal tissues that are predominantly affected in HD was explored. Green fluorescent protein was used as a reporter in each vector to show that both serotypes were broadly distributed in medium spiny neurons in the striatum and cortico-striatal neurons after infusion into the putamen and caudate nucleus of nonhuman primates (NHP), with AAV1-directed expression being slightly more robust than AAV2-driven expression. This study suggests that both serotypes are capable of targeting neurons that degenerate in HD, and it sets the stage for the advanced preclinical evaluation of an RNAi-based therapy for this disease.
Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo (2010)

A high plasma urate concentration (PUA), related to loss of urate oxidase in evolution, is postulated to protect humans from oxidative injury. This hypothesis has broad clinical relevance, but support rests largely on in vitro data and epidemiologic associations. Pegloticase therapy generates H(2)O(2) while depleting urate, offering an in vivo test of the antioxidant hypothesis. We show that erythrocytes can efficiently eliminate H(2)O(2) derived from urate oxidation to prevent cell injury in vitro; during therapy, disulfide-linked peroxiredoxin 2 dimer did not accumulate in red blood cells, indicating that their peroxidase capacity was not exceeded. To assess oxidative stress, we monitored F2-Isoprostanes (F2-IsoPs) and protein carbonyls (PC), products of arachidonic acid and protein oxidation, in plasma of 26 refractory gout patients receiving up to five infusions of pegloticase at 3-wk intervals. At baseline, PUA was markedly elevated in all patients, and plasma F2-IsoP concentration was elevated in most. Pegloticase infusion rapidly lowered mean PUA to < or = 1 mg/dL in all patients, and PUA remained low in 16 of 21 patients who completed treatment. F2-IsoP levels did not correlate with PUA and did not increase during 15 wk of sustained urate depletion. There also was no significant change in the levels of plasma PC. Because refractory gout is associated with high oxidative stress in spite of high PUA, and profoundly depleting uric acid did not increase lipid or protein oxidation, we conclude that urate is not a major factor controlling oxidative stress in vivo.
Ectopic bone formation using osteogenic protein‐1 carried by a solution precipitated hydroxyapatite (2004)

Solution precipitation of calcium and phosphate is a technique to generate hydroxyapatite [Peri-Apatitetrade mark (PA), Stryker Orthopaedics, Mahwah, NJ] on metal substrate. This study was carried out to determine the capacity of PA to adsorb osteogenic protein-1 (OP-1) and the time course of release, and to determine the osteoinductive activity of OP-1. The adsorption and release studies were conducted with (125)I-labeled OP-1- and PA-coated titanium alloy disks. The results indicate that the adsorption of OP-1 on the PA-coated disks is linear with the concentration of OP-1 up to 5 mg/mL. There is an initial release of 75% to 80% of adsorbed OP-1 within the first hour, and 92% of OP-1 is released in 3 days. The osteoinductive activity of OP-1 was determined in the rat intramuscular ectopic bone formation assay. A total of 24 titanium alloy disks were evenly divided into 3 groups with different treatments for implantation, plain disks (group A), disks coated with PA (group B), and disks coated with PA plus 40 microg OP-1 (group C). Osteogenic protein-1, 40 microg in solution, was injected into the muscle pouch in animals of group D (n = 8). The rats were sacrificed 3 weeks postoperatively and the implants were retrieved. Ectopic bone formation was evaluated with radiography and histology. Results demonstrated that OP-1 induced ectopic bone in all the animals of group C and group D. The titanium alloy disks were surrounded by trabecular bone and marrow tissue. None of the animals of group A or group B showed any evidence of osteoinduction. Our findings indicate that PA can deliver OP-1 directly to titanium alloy implants and maintain the osteoinductive activity of OP-1.
Hydride Abstraction Initiated Hydrosilylation of Terminal Alkenes and Alkynes on Porous Silicon (2002)

Hydride abstraction by triphenylcarbenium cations in the presence of terminal alkynes and alkenes results in hydrosilylation at room temperature on hydride-terminated porous silicon surfaces, leading to alkenyl- and alkyl-terminated surfaces, respectively. A wide range of surface terminations are possible as the reaction conditions tolerate a variety of functional groups. Silicon−carbon bond formation is substantiated by Fourier transform infrared and 13C solid-state NMR spectroscopies, in addition to chemical and stability studies. Generation of an energetic surface silicon-based positive charge is thus a viable route to the formation of silicon−carbon bonds via hydrosilylation, a step previously postulated for the mechanism of exciton-mediated hydrosilylation on photoluminescent nanocrystalline silicon.
Cell Adhesion to Fibrillin-1 Molecules and Microfibrils Is Mediated by α5β1 and αvβ3 Integrins (2003)

Fibrillins are the major glycoprotein components of microfibrils that form a template for tropoelastin during elastic fibrillogenesis. We have examined cell adhesion to assembled purified microfibrils, and its molecular basis. Human dermal fibroblasts exhibited Arg-Gly-Asp and cation-dependent adhesion to microfibrils and recombinant fibrillin-1 protein fragments. Strong integrin alpha 5 beta 1 interactions with fibrillin ligands were identified, but integrin alpha v beta 3 also contributed to cell adhesion. Fluorescence-activated cell sorting analysis confirmed the presence of abundant alpha 5 beta 1 and some alpha v beta 3 receptors on these cells. Adhesion to microfibrils and to Arg-Gly-Asp containing fibrillin-1 protein fragments induced signaling events that led to cell spreading, altered cytoskeletal organization, and enhanced extracellular fibrillin-1 deposition. Differences in cell shape when plated on fibrillin or fibronectin implied substrate-specific alpha 5 beta 1-mediated cellular responses. An Arg-Gly-Asp-independent cell adhesion sequence was also identified within fibrillin-1. Adhesion and spreading of smooth muscle cells on fibrillin ligands was enhanced by antibody-induced beta1 integrin activation. A375-SM melanoma cells bound Arg-Gly-Asp-containing fibrillin-1 protein fragments mainly through alpha v beta 3, whereas HT1080 cells used mainly alpha 5 beta 1. This study has shown that fibrillin microfibrils mediate cell adhesion, that alpha 5 beta 1 and alpha v beta 3 are both important but cell-specific fibrillin-1 receptors, and that cellular interactions with fibrillin-1 influence cell behavior.
ACS NEWS (2009)

RETURN TO ISSUEPREVACS NewsNEXTACS NEWSSOPHIE ROVNERCite this: Chem. Eng. News 2009, 87, 21, 44Publication Date (Print):May 25, 2009Publication History Published online14 November 2010Published inissue 25 May 2009https://pubs.acs.org/doi/10.1021/cen-v087n021.p044https://doi.org/10.1021/cen-v087n021.p044acs-newsACS PublicationsCopyright © 2009 AMERICAN CHEMICAL SOCIETY. This publication is available under these Terms of Use. This publication is free to access through this site. Learn MoreArticle Views70Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (363 KB) SUBJECTS:Physical chemistry Get e-Alerts
Differential Gene Expression Patterns in Chicken Cardiomyocytes during Hydrogen Peroxide-Induced Apoptosis (2016)

Hydrogen peroxide (H2O2) is both an exogenous and endogenous cytotoxic agent that can reliably induce apoptosis in numerous cell types for studies on apoptosis signaling pathways. However, little is known of these apoptotic processes in myocardial cells of chicken, a species prone to progressive heart failure. Sequencing of mRNA transcripts (RNA-Seq) allows for the identification of differentially expressed genes under various physiological and pathological conditions to elucidate the molecular pathways involved, including cellular responses to exogenous and endogenous toxins. We used RNA-seq to examine genes differentially expressed during H2O2-induced apoptosis in primary cultures of embryonic chicken cardiomyocytes. Following control or H2O2 treatment, RNA was extracted and sequencing performed to identify novel transcripts up- or downregulated in the H2O2 treatment group and construct protein-protein interaction networks. Of the 19,268 known and 2,160 novel transcripts identified in both control and H2O2 treatment groups, 4,650 showed significant differential expression. Among them, 55.63% were upregulated and 44.37% downregulated. Initiation of apoptosis by H2O2 was associated with upregulation of caspase-8, caspase-9, and caspase-3, and downregulation of anti-apoptotic genes API5 and TRIA1. Many other differentially expressed genes were associated with metabolic pathways (including 'Fatty acid metabolism', 'Alanine, aspartate, and glutamate metabolism', and 'Biosynthesis of unsaturated fatty acids') and cell signaling pathways (including 'PPAR signaling pathway', 'Adipocytokine signaling pathway', 'TGF-beta signaling pathway', 'MAPK signaling pathway', and 'p53 signaling pathway'). In chicken cardiomyocytes, H2O2 alters the expression of numerous genes linked to cell signaling and metabolism as well as genes directly associated with apoptosis. In particular, H2O2 also affects the biosynthesis and processing of proteins and unsaturated fatty acids. These results highlight the value of RNA-seq for revealing unexpected molecular contributors to oxidative stress responses, thereby identifying novel potential therapeutic targets.