gebhart/patrepeval huggingface dataset:
High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheumatic disease (2008)

High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein that has a dual function. Inside the cell, HMGB1 binds DNA, regulating transcription and determining chromosomal architecture. Outside the cell, HMGB1 can serve as an alarmin to activate the innate system and mediate a wide range of physiological and pathological responses. To function as an alarmin, HMGB1 translocates from the nucleus of the cell to the extra-cellular milieu, a process that can take place with cell activation as well as cell death. HMGB1 can interact with receptors that include RAGE (receptor for advanced glycation endproducts) as well as Toll-like receptor-2 (TLR-2) and TLR-4 and function in a synergistic fashion with other proinflammatory mediators to induce responses. As shown in studies on patients as well as animal models, HMGB1 can play an important role in the pathogenesis of rheumatic disease, including rheumatoid arthritis, systemic lupus erythematosus, and polymyositis among others. New approaches to therapy for these diseases may involve strategies to inhibit HMGB1 release from cells, its interaction with receptors, and downstream signaling.
Biofilm delays wound healing: A review of the evidence (2013)

Biofilm is the predominant mode of life for bacteria and today it is implicated in numerous human diseases. A growing body of scientific and clinical evidence now exists regarding the presence of biofilm in wounds. This review summarizes the clinical experiences and in vivo evidence that implicate biofilm in delayed wound healing. The various mechanisms by which biofilm may impede healing are highlighted, including impaired epithelialization and granulation tissue formation, and reduced susceptibilities to antimicrobial agents and host defenses. Strategies to manage biofilm and encourage progression to wound healing are discussed; these include debridement and appropriate antimicrobial therapies which may be improved upon in the future with the emergence of anti-biofilm technologies.
Human interferon gamma potently induces the synthesis of a 55-kDa protein (gamma 2) highly homologous to rabbit peptide chain release factor and bovine tryptophanyl-tRNA synthetase. (1991)

An interferon gamma (IFN-gamma)-inducible protein, gamma 2, was identified by two-dimensional gel electrophoresis of transformed human amnion (AMA) cell proteins. cDNA clones coding for this protein have been isolated and characterized as encoding a polypeptide with a predicted molecular weight of 53,165 and a pI of 6.16. Both values are in good agreement with those observed in two-dimensional gel electrophoresis. The gamma 2 protein is found to be highly induced by IFN-gamma, whereas no induction was seen after addition of IFN-alpha to AMA cells. A gamma 2-specific 2.7-kilobase mRNA was likewise seen to accumulate selectively in response to IFN-gamma in these cells. Comparison of the predicted amino acid sequence of gamma 2 to proteins in GenBank data bases revealed that gamma 2 is highly homologous to rabbit peptide chain release factor [Lee, C. C., Craigen, W. J., Muzny, D. M., Harlow, E. & Caskey, C. T. (1990) Proc. Natl. Acad. Sci. USA 87, 3508-3512] and bovine tryptophanyl-tRNA synthetase [M. Garret, V. Trezeguet, B. Pajot, J. C. Gandar, M. Merle, M. Guegiev, J. P. Benedetto, C. Sarger, J. Alteriot, J. La Bouessec, J. Labouesse, and J. Bonnet (1990), GenBank accession no. X52113]. Amino acid sequence similarities of 94% and 97%, respectively, are found, which in general would indicate that gamma 2 represents the human equivalent to either of these two mammalian genes. Based on these sequence similarities, the current data raise the possibility that tryptophanyl-tRNA charging and peptide chain release are carried out by the same enzyme. The gamma 2 protein is shown to possess tryptophan-dependent aminoacyl-tRNA synthetase activity and thus constitutes an enzymatic activity involved in the biological activity of IFN-gamma.
MRI and Characterization of Atherosclerotic Plaque (2002)

Noninvasive high-resolution magnetic resonance has the potential to image atherosclerotic plaque and to determine its composition and microanatomy. This review summarizes the rationale for plaque imaging and describes the characteristics of plaque by use of existing MRI techniques. The use of MRI in human disease and in animal models, particularly in rabbits and mice, is presented. Present and future applications of MRI, including real-time vascular intervention, new contrast agents, and molecular imaging, are also discussed.
Domain structure of an N-ethylmaleimide-sensitive fusion protein involved in vesicular transport. (1993)

N-Ethylmaleimide-sensitive fusion protein (NSF) is an essential component for protein transport between Golgi cisternae. Sequence analysis and proteolytic dissection reveal that NSF contains two tandem "ATP domains," each containing the consensus sequence for the binding of nucleotide. When Escherichia coli-produced Chinese hamster ovary NSF is purified, it exhibits a low, but significant, ATPase activity. The ATPase activity of NSF is sensitive to N-ethylmaleimide and influenced by monoclonal antibodies against recombinant NSF.
Introduction (2003)

Abstract This introductory chapter begins with a discussion on the relationship between democratization and women’s access to political power in post-communist systems, and gender equality in politics. It then describes the general framework model on legislative recruitment that will be applied in the 12 case studies on female legislative representation in post-communist Europe featured in the volume. An overview of the cases, and their conclusions are presented.
Angiotensin II Receptor Antagonists and Angiotensin-Converting Enzyme Inhibitors Lower In Vitro the Formation of Advanced Glycation End Products (2002)

The implication of advanced glycation end products (AGE) in the pathogenesis of atherosclerosis and of diabetic and uremic complications has stimulated a search for AGE inhibitors. This study evaluates the AGE inhibitory potential of several well-tolerated hypotensive drugs. Olmesartan, an angiotensin II type 1 receptor (AIIR) antagonist, as well as temocaprilat, an angiotensin-converting enzyme (ACE) inhibitor, unlike nifedipine, a calcium blocker, inhibit in vitro the formation of two AGE, pentosidine and N(epsilon)-carboxymethyllysine (CML), during incubation of nonuremic diabetic, nondiabetic uremic, or diabetic uremic plasma or of BSA fortified with arabinose. This effect is shared by all tested AIIR antagonists and ACE inhibitors. On an equimolar basis, they are more efficient than aminoguanidine or pyridoxamine. Unlike the latter two compounds, they do not trap reactive carbonyl precursors for AGE, but impact on the production of reactive carbonyl precursors for AGE by chelating transition metals and inhibiting various oxidative steps, including carbon-centered and hydroxyl radicals, at both the pre- and post-Amadori steps. Their effect is paralleled by a lowered production of reactive carbonyl precursors. Finally, they do not bind pyridoxal, unlike aminoguanidine. Altogether, this study demonstrates for the first time that widely used hypotensive agents, AIIR antagonists and ACE inhibitors, significantly attenuate AGE production. This study provides a new framework for the assessment of families of AGE-lowering compounds according to their mechanisms of action.
Effect of polyanions on the unfolding of acidic fibroblast growth factor (1993)

The urea-induced unfolding of acidic fibroblast growth factor (aFGF) in the presence and absence of various polyanions has been quantitatively examined by fluorescence spectroscopy. In the absence of a stabilizing polyanion, the apparent free energy of unfolding of aFGF is 6.5 kcal mol-1. The presence of equimolar or greater amounts of heparin stabilizes aFGF from unfolding by more than 2.5 kcal mol-1 and slows the rate of unfolding by greater than 2000-fold. The ability of heparin to stabilize aFGF is critically dependent upon many factors including the number of aFGF molecules bound to the heparin chain, ionic strength, temperature, and the extent of sulfation of the polysaccharide. The presence of similar amounts of other polyanions such as sulfated beta-cyclodextrin or heparan sulfate also stabilizes aFGF to a similar extent as heparin. Additional experiments demonstrate that increasing charge density enhances the ability of polyanions such as sulfated beta-cyclodextrins, phosphorylated inositols, and modified heparins to protect aFGF from urea-induced unfolding.
The Enhancer of split complex and adjacent genes in the 96F region of Drosophila melanogaster are required for segregation of neural and epidermal progenitor cells. (1992)

The Enhancer of split complex [E(spl)-C] of Drosophila melanogaster is located in the 96F region of the third chromosome and comprises at least seven structurally related genes, HLH-m delta, HLH-m gamma, HLH-m beta, HLH-m3, HLH-m5, HLH-m7 and E(spl). The functions of these genes are required during early neurogenesis to give neuroectodermal cells access to the epidermal pathway of development. Another gene in the 96F region, namely groucho, is also required for this process. However, groucho is not structurally related to, and appears to act independently of, the genes of the E(spl)-C; the possibility is discussed that groucho acts upstream to the E(spl)-C genes. Indirect evidence suggests that a neighboring transcription unit (m4) may also take part in the process. Of all these genes, only gro is essential; m4 is a dispensable gene, the deletion of which does not produce detectable morphogenetic abnormalities, and the genes of the E(spl)-C are to some extent redundant and can partially substitute for each other. This redundancy is probably due to the fact that the seven genes of the E(spl)-C encode highly conserved putative DNA-binding proteins of the bHLH family. The genes of the complex are interspersed among other genes which appear to be unrelated to the neuroepidermal lineage dichotomy.
ICAM-1-Coupled Cytoskeletal Rearrangements and Transendothelial Lymphocyte Migration Involve Intracellular Calcium Signaling in Brain Endothelial Cell Lines (2000)

Endothelium of the cerebral blood vessels, which constitutes the blood-brain barrier, controls adhesion and trafficking of leukocytes into the brain. Investigating signaling pathways triggered by the engagement of adhesion molecules expressed on brain endothelial cells using two rat brain endothelial cell lines (RBE4 and GP8), we report in this paper that ICAM-1 cross-linking induces a sustained tyrosine phosphorylation of the phosphatidylinositol-phospholipase C (PLC)gamma1, with a concomitant increase in both inositol phosphate production and intracellular calcium concentration. Our results suggest that PLC are responsible, via a calcium- and protein kinase C (PKC)-dependent pathway, for p60Src activation and tyrosine phosphorylation of the p60Src substrate, cortactin. PKCs are also required for tyrosine phosphorylation of the cytoskeleton-associated proteins, focal adhesion kinase and paxillin, but not for ICAM-1-coupled p130Cas phosphorylation. PKC's activation is also necessary for stress fiber formation induced by ICAM-1 cross-linking. Finally, cell pretreatment with intracellular calcium chelator or PKC inhibitors significantly diminishes transmonolayer migration of activated T lymphocytes, without affecting their adhesion to brain endothelial cells. In summary, our data demonstrate that ICAM-1 cross-linking induces calcium signaling which, via PKCs, mediates phosphorylation of actin-associated proteins and cytoskeletal rearrangement in brain endothelial cell lines. Our results also indicate that these calcium-mediated intracellular events are essential for lymphocyte migration through the blood-brain barrier.
TNF receptor superfamily‐induced cell death: redox‐dependent execution (2006)

Tumor necrosis factor (TNF) superfamily is a group of cytokines with important functions in immunity, inflammation, differentiation, control of cell proliferation, and apoptosis. TNFalpha is the founding member of the 19 different proteins that have so far been identified within this family. TNF family members exert their biological effects through the TNF receptor (TNFR) superfamily of cell surface receptors that share a stretch of approximately 80 amino acids within their cytoplasmic region, the death domain (DD), critical for recruiting the death machinery. Work over the last decade has unraveled critical signaling networks involved in TNFR-induced cell death, specifically using the constitutively expressed TNFR1 as a prototype. Of particular interest is the intermediary role of intracellular reactive oxygen species (ROS) in signal transduction after ligation of the TNFR1. With the increasing understanding of the of death receptor signaling pathways, the exact role of ROS in TNFalpha-induced execution is now believed to be far more complicated than originally thought. Recently, some important discoveries have underscored the critical role of ROS in TNFalpha signaling, notably in TNFalpha-mediated activation of nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (c-Jun NH2-terminal kinase, JNK), as well as in cell death (apoptotic and necrotic) pathways. Here we attempt to review the existing knowledge on the involvement of ROS in death receptor signaling using TNFalpha-TNFR1 as the model system, specifically addressing the involvement of intracellular ROS in TNFalpha-induced cell death and in TNFalpha-induced activation of NF-kappaB and JNK and their crosstalk.
Improved CUT&RUN chromatin profiling tools (2019)

Previously, we described a novel alternative to chromatin immunoprecipitation, CUT&RUN, in which unfixed permeabilized cells are incubated with antibody, followed by binding of a protein A-Micrococcal Nuclease (pA/MNase) fusion protein (Skene and Henikoff, 2017). Here we introduce three enhancements to CUT&RUN: A hybrid protein A-Protein G-MNase construct that expands antibody compatibility and simplifies purification, a modified digestion protocol that inhibits premature release of the nuclease-bound complex, and a calibration strategy based on carry-over of <i>E. coli</i> DNA introduced with the fusion protein. These new features, coupled with the previously described low-cost, high efficiency, high reproducibility and high-throughput capability of CUT&RUN make it the method of choice for routine epigenomic profiling.
The RCSB Protein Data Bank: a redesigned query system and relational database based on the mmCIF schema (2004)

The Protein Data Bank (PDB) is the central worldwide repository for three-dimensional (3D) structure data of biological macromolecules. The Research Collaboratory for Structural Bioinformatics (RCSB) has completely redesigned its resource for the distribution and query of 3D structure data. The re-engineered site is currently in public beta test at http://pdbbeta.rcsb.org. The new site expands the functionality of the existing site by providing structure data in greater detail and uniformity, improved query and enhanced analysis tools. A new key feature is the integration and searchability of data from over 20 other sources covering genomic, proteomic and disease relationships. The current capabilities of the re-engineered site, which will become the RCSB production site at http://www.pdb.org in late 2005, are described.
A novel combined chemical-enzymic synthesis of crosslinked DNA using a nucleoside triphosphate analog (1991)

A novel method using combined chemical and enzymatic reactions to allow the preparation of covalently cross-linked DNA duplexes has been described. The method can be used to specifically link two complementary bases of a DNA duplex containing all four natural bases. The modified nucleotide 9-(2-deoxy-5-O-triphospho-beta-D-ribofuranosyl)-N6,N6-ethano -2,6-diaminopurine (6edDTP) was prepared by total chemical synthesis and was found to be incorporated into DNA duplexes in the place of 2'-deoxyguanosine 5'-O-triphosphate by the Klenow fragment of Escherichia coli DNA polymerase I, T4 and T7 DNA polymerases, avian myeloma virus reverse transcriptase, and rat DNA polymerase beta. Once incorporated, the aziridine of the nucleotide is rapidly opened by the N4 of the cytosine on the complementary strand to give cross-linked DNA, where the modified nucleotide is covalently joined to the complementary base by an ethano linkage. The duplexes produced were found to be recognized as substrates by various DNA polymerases. The Km for the incorporation of the 6edDTP into DNA catalyzed by the Klenow fragment of E. coli DNA polymerase I was found to be 29 microM, and the kcat was found to be 0.014 s-1. The modified nucleoside also served as a substrate for terminal deoxynucleotidyltransferase, where it was added to single-stranded DNA and then hybridized to a complementary strand, after which cross-linking of the two strands occurred within 1 min.
Coupling profile and historical methods to predictexecution time of parallel applications (2013)

International audience
Design and development of passive MEMS-IDT sensors for continuous monitoring of tire pressure (2001)

In this paper, design and development of polymeric based MEMS-IDT based passive microsensors for continuous monitoring of tire pressure is presented. The sensing system uses SAW sensor mounted on the tire valve stem which is interrogated with an antenna controlled from the dash-board of the car. This unique combination of technologies results in a novel tire pressure sensor that can be remotely sensed by a RF system with the advantage of no power requirements at the sensor site. The sensor presented is simple in construction and easy to manufacture with Microstereo Lithography. The sensors are programmable and can be identified with a bar-code. Thus the technology will not only alert drivers to potential problems, but also will identify which tire is involved.
Structure of the human gene encoding the invariant γ-chain of class II histocompatibility antigens (1985)

The primary structures of a cDNA and the genomic DNA of a gene selectively expressed in chronic lymphocytic leukemia were determined. A computer search of the nucleotide sequence data bank identified this gene as the invariant gamma-chain associated with class II histocompatibility antigens. The invariant gamma-chain genomic sequence spans about 11 kilobases, with eight exons and seven introns. Three of the introns contain members of the Alu repeat family. A putative cap site and promoter sequence were identified at the 5' end of the gene. One or two copies of the gene is present in each haploid genome, and no evidence for amplification or polymorphism was obtained.
Photophysical Properties of Coumarin-152 and Coumarin-481 Dyes:  Unusual Behavior in Nonpolar and in Higher Polarity Solvents (2003)

Solvent polarity and temperature effect on the photophysical properties of two 1,2-benzopyrone dyes, namely, coumarin-152 (C152) and coumarin-481 (C481), have been investigated using steady-state and time-resolved fluorescence measurements. In nonpolar (NP) solvents (e.g., hexane, cyclohexane, methylcyclohexane, 2-methylpentane, and 3-methylpentane), the Stokes' shifts (Δν̄) and fluorescence lifetimes (τf) for both the dyes are unexpectedly lower. Excluding NP solvents, for all other solvents the Δν̄ correlates linearly with the solvent polarity function, Δf = {(ε − 1)/(2ε + 1) − (n2 − 1)/(2n2 + 1)}, and the slopes of these plots indicate that the fluorescent states for both the dyes in these solvents are of intramolecular charge transfer (ICT) character. The unusually lower Δν̄ and τf values in NP solvents have been rationalized considering nonpolar structures for the fluorescent states of the dyes in these solvents. The fluorescence quantum yields (Φf) and τf values of the two dyes also show an unusual reduction in higher polarity solvents (Δf > ∼0.2). Furthermore, unlike in all other solvents, in solvents with Δf > ∼0.2, the Φf and τf values are strongly temperature-dependent. These results indicated the involvement of a new activation-controlled nonradiative deexcitation channel in higher polarity solvents, assigned to the involvement of the nonfluorescent twisted intramolecular charge transfer (TICT) state. Though the activation barrier (ΔEa) for such processes usually decreases with solvent polarity, for the present systems the ΔEa is seen to increase with Δf. This unusual behavior has been rationalized assuming that the ΔEa arises because of the potential energy (PE) crossing of the TICT and ground states rather than that of the ICT and TICT states as is usually the case for most TICT molecules. On increasing Δf, since the highly polar TICT state not only gets better stabilization but also its PE surface becomes more steeper than the ICT state, the ΔEa effectively increases with solvent polarity.
Polyhedral Shapes of CeO2 Nanoparticles (2003)

Ceria nanoparticles are a widely used nanomaterial for applications in catalysts, fuel cell, and microelectronics. An important factor that influences the performance of CeO2 is the particle shape. In this paper, a systematic study has been carried out to determine the shapes of CeO2 nanoparticles. For particles in the size range of 3−10 nm, the particle shape is dominated by truncated octahedral that is defined by the {100} and {111} facets. The fastest growth of the nanoparticles along 〈100〉 results in the disappearance of the {100} facets; thus, the large size CeO2 particles are dominated by the octahedral shape with flat surfaces. The nanoparticles agglomerate by minimizing the interface energy with the formation of a lattice matched “coherent interface”. The faceted shape also results in the textured distribution of nanoparticles deposited onto a substrate surface, with a preferred orientation of [110]. These structural characteristics are likely to affect their performance in technological applications.
Role of Pore-Forming Toxins in Bacterial Infectious Diseases (2013)

Pore-forming toxins (PFTs) are the most common bacterial cytotoxic proteins and are required for virulence in a large number of important pathogens, including Streptococcus pneumoniae, group A and B streptococci, Staphylococcus aureus, Escherichia coli, and Mycobacterium tuberculosis. PFTs generally disrupt host cell membranes, but they can have additional effects independent of pore formation. Substantial effort has been devoted to understanding the molecular mechanisms underlying the functions of certain model PFTs. Likewise, specific host pathways mediating survival and immune responses in the face of toxin-mediated cellular damage have been delineated. However, less is known about the overall functions of PFTs during infection in vivo. This review focuses on common themes in the area of PFT biology, with an emphasis on studies addressing the roles of PFTs in in vivo and ex vivo models of colonization or infection. Common functions of PFTs include disruption of epithelial barrier function and evasion of host immune responses, which contribute to bacterial growth and spreading. The widespread nature of PFTs make this group of toxins an attractive target for the development of new virulence-targeted therapies that may have broad activity against human pathogens.