gebhart/patrepeval huggingface dataset:
Forced expression of dystrophin deletion constructs reveals structure-function correlations. (1996)

Dystrophin plays an important role in skeletal muscle by linking the cytoskeleton and the extracellular matrix. The amino terminus of dystrophin binds to actin and possibly other components of the subsarcolemmal cytoskeleton, while the carboxy terminus associates with a group of integral and peripheral membrane proteins and glycoproteins that are collectively known as the dystrophin-associated protein (DAP) complex. We have generated transgenic/mdx mice expressing "full-length" dystrophin constructs, but with consecutive deletions within the COOH-terminal domains. These mice have enabled analysis of the interaction between dystrophin and members of the DAP complex and the effects that perturbing these associations have on the dystrophic process. Deletions within the cysteine-rich region disrupt the interaction between dystrophin and the DAP complex, leading to a severe dystrophic pathology. These deletions remove the beta-dystroglycan-binding site, which leads to a parallel loss of both beta-dystroglycan and the sarcoglycan complex from the sarcolemma. In contrast, deletion of the alternatively spliced domain and the extreme COOH terminus has no apparent effect on the function of dystrophin when expressed at normal levels. The proteins resulting from these latter two deletions supported formation of a completely normal DAP complex, and their expression was associated with normal muscle morphology in mdx mice. These data indicate that the cysteine-rich domain is critical for functional activity, presumably by mediating a direct interaction with beta-dystroglycan. However, the remainder of the COOH terminus is not required for assembly of the DAP complex.
Lysine-Specific Demethylase 1A (KDM1A/LSD1): Product Recognition and Kinetic Analysis of Full-Length Histones (2015)

Lysine-specific demethylase 1A (KDM1A/LSD1) is a FAD-dependent enzyme that catalyzes the oxidative demethylation of histone H3K4me1/2 and H3K9me1/2 repressing and activating transcription, respectively. Although the active site is expanded compared to that of members of the greater amine oxidase superfamily, it is too sterically restricted to encompass the minimal 21-mer peptide substrate footprint. The remainder of the substrate/product is therefore expected to extend along the surface of KDM1A. We show that full-length histone H3, which lacks any posttranslational modifications, is a tight-binding, competitive inhibitor of KDM1A demethylation activity with a Ki of 18.9 ± 1.2 nM, a value that is approximately 100-fold higher than that of the 21-mer peptide product. The relative H3 affinity is independent of preincubation time, suggesting that H3 rapidly reaches equilibrium with KDM1A. Jump dilution experiments confirmed the increased binding affinity of full-length H3 was at least partially due to a slow off rate (koff) of 1.2 × 10(-3) s(-1), corresponding to a half-life (t1/2) of 9.63 min, and a residence time (τ) of 13.9 min. Independent affinity capture surface plasmon resonance experiments confirmed the tight-binding nature of the H3/KDM1A interaction, revealing a Kd of 9.02 ± 2.3 nM, a kon of (9.3 ± 1.5) × 10(4) M(-1) s(-1), and a koff of (8.4 ± 0.3) × 10(-4) s(-1). Additionally, no other core histones exhibited inhibition of KDM1A demethylation activity, which is consistent with H3 being the preferred histone substrate of KDM1A versus H2A, H2B, and H4. Together, these data suggest that KDM1A likely contains a histone H3 secondary specificity element on the enzyme surface that contributes significantly to its recognition of substrates and products.
A single-phase photovoltaic inverter topology with a series-connected power buffer (2010)

Module integrated converters (MICs) have been under rapid developement for single-phase grid-tied photovoltaic applications. The capacitive energy storage implementation for the double-line-frequency power variation represents a differentiating factor among existing designs. This paper introduces a new topology that places the energy storage block in a series-connected path with the line interface block. This design provides independent control over the capacitor voltage, soft-switching for all semiconductor devices, and full four-quadrant operation with the grid. The proposed approach is analyzed and experimentally demonstrated.
Polarization and angular effects of femtosecond laser-induced conical microstructures on Ni (2012)

In this paper, through femtosecond laser pulse irradiation with various polarizations and incident angles, we create arrays of nanostructure-covered conical microstructures (NC-CMs) on Ni. We show that the shape of CMs depends significantly on the polarization and incident angle of the laser beam, and find that the size of nanostructures is distributed asymmetrically on the CMs at off normal incidence. We suggest that nonuniform energy deposition owing to the polarization and the incident angle of laser beam plays an important role in the asymmetric nanostructure distribution and shape of CMs on Ni.
STAT-3 regulates surfactant phospholipid homeostasis in normal lung and during endotoxin-mediated lung injury (2008)

Acute lung injury associated with surfactant deficiency remains a major cause of pulmonary morbidity and mortality. Since signal transducer and activator of transcription-3 (STAT-3) plays an important role in protecting respiratory epithelial cells during injury, we hypothesized that STAT-3 may regulate gene expression in type II cells that mediate surfactant phospholipid synthesis. Conditional deletion of Stat-3 in respiratory epithelial cells in the lung of transgenic mice (Stat-3(Delta/Delta) mice) decreased surfactant phospholipid synthesis and secretion. Deletion of Stat-3 was associated with decreased expression of Akt2, Srebf-1, and other genes expressed in type II cells that may influence surfactant phospholipid synthesis (Glut-1, Slc34a2, Gpam, Acox2, and Cds2). Stat-3(Delta/Delta) mice were more susceptible to intratracheal lipopolysaccharide (LPS). Saturated phosphatidylcholine and surfactant protein B levels were significantly decreased in bronchoalveolar lavage fluid from LPS-treated Stat-3(Delta/Delta) mice. Alveolar capillary leak, proinflammatory cytokine expression, and perturbations of lung mechanics caused by LPS were exacerbated after deletion of STAT-3. STAT-3 plays a critical role in the regulation of surfactant lipid synthesis in the normal lung and during lung injury caused by LPS.
Relative Bioavailability of a Paediatric Granule Formulation of the HIV Integrase Inhibitor Dolutegravir in Healthy Adult Subjects (2013)

The exposure of dolutegravir after administration of granule formulation alone, with different types of water and with milk formula, exceeded that of the tablet. The similarity of dolutegravir exposure seen with the granule formulation demonstrates that dolutegravir granule can be given without restriction on the type of liquid or can be administered directly to the mouth (for example, when potable water is not available).
MO CVD of Noble Metals (1995)

The state of the art in research and application of processes of chemical vapour deposition of noble metal (Pt, Pd, Rh, Ir, Ru, Au) coatings is considered. Systematization of known experimental data on synthesis, thermal properties and saturated vapour pressure of volatile compounds of noble metals with organic ligands is provided. The processes of CVD of noble metals were analized from general requirements to precursors. It is shown that chelate or mixed-ligand noble metal complexes and, in particular [MATH]-diketonate derivatives due to their thermal properties are the most suitable for deposition of noble metal thick films.
Absence of the P2X7 Receptor Alters Leukocyte Function and Attenuates an Inflammatory Response (2002)

When challenged with extracellular ATP, leukocytes respond and activate processes attributed to the P2X(7) receptor (P2X(7)R), an unusual ligand-gated ion channel. To prove P2X(7)R involvement, blood samples from P2X(7)R-deficient mice were characterized. Monocytes and lymphocytes associated with wild-type blood responded to ATP and underwent volume/shape changes and shed L-selectin. In contrast, leukocytes from P2X(7)R-deficient animals demonstrated no change in physical properties or L-selectin expression following ATP challenge. Blood stimulated with LPS or ATP individually generated minimal quantities of the leaderless polypeptide IL-1 beta, but sequential treatment of wild-type, but not P2X(7)R-deficient, blood with LPS and ATP yielded large amounts of cell-free cytokine. Based on these differences, wild-type and P2X(7)R-deficient animals were compared following induction of monoclonal anti-collagen-induced arthritis. Ab-treated wild-type animals subsequently challenged with LPS developed inflamed, swollen paws; their joint cartilage demonstrated lesions, loss of proteoglycan content, and the presence of collagen degradation products. P2X(7)R-deficient animals subjected to the same challenge were markedly less affected; both the incidence and severity of disease were reduced. These data indicate that ATP does act via the P2X(7)R to affect leukocyte function and that the P2X(7)R can serve as an important component of an in vivo inflammatory response.
Synthesis, X-ray Structure, and Electrochemical and Excited-State Properties of Multicomponent Complexes Made of a [Ru(Tpy)2]2+ Unit Covalently Linked to a [2]-Catenate Moiety. Controlling the Energy-Transfer Direction by Changing the Catenate Metal Ion (1999)

New multicomponent species consisting of [2]-catenates incorporating the [Ru(tpy)2]2+ moiety (tpy = 2,2‘:6‘,2‘ ‘-terpyridine) within their framework have been prepared, and their electrochemical and photophysical properties have been studied. The parent compound of the investigated species is a previously described Cu(I) catenate (RuCu) containing a [Cu(dap)2]+ fragment (dap = 2,9-dianisyl-1,10-phenanthroline) used as a template and a [Ru(tpy)2]2+ unit integrating one of the interlocked rings. Selective demetalation of the Cu(I) catenate moiety of RuCu afforded a catenand (Ru) containing the [Ru(tpy)2]2+-type component and a free tetrahedral coordination site. Reaction of this catenand with Ag+ and Zn2+ ions yielded two new bimetallic catenates (RuAg and RuZn, respectively). The solid-state structure of complexes RuCu and RuAg has been determined by X-ray diffraction. Electrochemical experiments have shown that the two moieties of the RuCu and RuAg catenates undergo independent redox processes. The photophysical properties of Ru, RuCu, RuZn, and RuAg have been investigated by steady-state and time-resolved techniques, and compared with those of appropriate model compounds. The absorption spectra do not show any appreciable ground-state electronic interactions between the [2]-catM (cat = catenand, catM = catenate) and [Ru(tpy)2]2+-type moieties, whereas luminescence properties reveal the occurrence of efficient photoinduced intercomponent energy- and/or electron-transfer processes, whose direction depends on the presence or on the nature of the metal ion in the [2]-cat-type moiety. In Ru, RuZn, and RuAg such a moiety is quenched by the [Ru(tpy)2]2+ unit, whereas for RuCu the opposite behavior is observed. The rate constant of intercomponent processes are determined via time-resolved nano- and picosecond luminescence spectroscopy.
Chemoenzymatic Synthesis of 11-cis-Retinal Photoaffinity Analog by Use of Squid Retinochrome (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTChemoenzymatic Synthesis of 11-cis-Retinal Photoaffinity Analog by Use of Squid RetinochromeBabak Borhan, Roxanne Kunz, Andrew Y. Wang, Koji Nakanishi, Nina Bojkova, and Kazuo YoshiharaView Author Information Department of Chemistry, Columbia University New York, New York 10027 Suntory Institute for Bioorganic Research Osaka, Japan Cite this: J. Am. Chem. Soc. 1997, 119, 24, 5758–5759Publication Date (Web):June 18, 1997Publication History Received26 March 1997Published online18 June 1997Published inissue 1 June 1997https://pubs.acs.org/doi/10.1021/ja970956ihttps://doi.org/10.1021/ja970956irapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views256Altmetric-Citations12LEARN 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 Other access optionsGet e-Alertsclose SUBJECTS:Chromophores,Isomerization,Molecular structure,Peptides and proteins,Photoisomerization Get e-Alerts
Development of a specific system for targeting protein to metallophilic macrophages (2004)

The cysteine-rich domain (CR) of the mannose receptor binds sulfated glycoprotein CR ligand (CRL) expressed by subpopulations of myeloid cells in secondary lymphoid organs (CRL(+) cells). In naïve mice, these CRL(+) cells, metallophilic macrophages (M) in spleen and subcapsular sinus M in lymph nodes, are located strategically for antigen capture and are adjacent to B cell follicles, but their role in the immune response is unknown. We have exploited the lectin activity of CR to develop a highly specific system for targeting protein to CRL(+) M. We demonstrate that the sulfated carbohydrates recognized by CR are exposed to the extracellular milieu and mediate highly specific targeting of CR-containing proteins. This model will allow the dissection of the role of metallophilic M in an immune response in vivo.
Bin3 Deletion Causes Cataracts and Increased Susceptibility to Lymphoma during Aging (2008)

Bin3 encodes an evolutionarily conserved and ubiquitously expressed member of the BAR superfamily of curved membrane and GTPase-binding proteins, which includes the BAR, PCH/F-BAR, and I-BAR adapter proteins implicated in signal transduction and vesicular trafficking. In humans, Bin3 maps to chromosome 8p21.3, a region widely implicated in cancer suppression that is often deleted in non-Hodgkin's lymphomas and various epithelial tumors. Yeast studies have suggested roles for this gene in filamentous actin (F-actin) organization and cell division but its physiologic functions in mammals have not been investigated. Here we report that homozygous inactivation of Bin3 in the mouse causes cataracts and an increased susceptibility to lymphomas during aging. The cataract phenotype was marked by multiple morphologic defects in lens fibers, including the development of vacuoles in cortical fibers and a near total loss of F-actin in lens fiber cells but not epithelial cells. Through 1 year of age, no other phenotypes were apparent; however, by 18 months of age, Bin3(-/-) mice exhibited a significantly increased incidence of lymphoma. Bin3 loss did not affect normal cell proliferation, F-actin organization, or susceptibility to oncogenic transformation. In contrast, it increased the proliferation and invasive motility of cells transformed by SV40 large T antigen plus activated ras. Our findings establish functions for Bin3 in lens development and cancer suppression during aging. Further, they define Bin3 as a candidate for an unidentified tumor suppressor that exists at the human chromosome 8p21.3 locus.
Formaldehyde Crosslinking: A Tool for the Study of Chromatin Complexes (2015)

Formaldehyde has been used for decades to probe macromolecular structure and function and to trap complexes, cells, and tissues for further analysis. Formaldehyde crosslinking is routinely employed for detection and quantification of protein-DNA interactions, interactions between chromatin proteins, and interactions between distal segments of the chromatin fiber. Despite widespread use and a rich biochemical literature, important aspects of formaldehyde behavior in cells have not been well described. Here, we highlight features of formaldehyde chemistry relevant to its use in analyses of chromatin complexes, focusing on how its properties may influence studies of chromatin structure and function.
Biology, Clinical Course and Management of Nodular Lymphocyte-Predominant Hodgkin Lymphoma (2006)

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) differs in histological and clinical presentation from classical Hodgkin lymphoma (cHL). The typical morphologic signs of NLPHL are atypical "lymphocytic and histiocytic" (L&H) cells, which are surrounded by a non-neoplastic nodular background of small lymphocytes of B-cell origin. The NLPHL cells are positive for CD45, CD19, CD20, CD22 and CD79a, but lack expression of CD15 and CD30, the typical markers for cHL. NLPHL patients are predominantly of male gender with a median age of 37 years. Patients often present in early stages (63%) and rarely have B-symptoms (9%). Treatment of NLPHL patients using standard Hodgkin lymphoma (HL) protocols leads to complete remission (CR) in more than 95% of patients. Survival and freedom from treatment failure (FFTF) are worse in advanced-stage patients than in early-stage patients. Thus, patients in advanced and in early stages with unfavorable risk factors are treated similarly to cHL patients. In contrast, patients with early-stage NLPHL without risk factors can be sufficiently treated with reduced intensity programs having less severe adverse effects. As a result, treatment of early NLPHL is less clearly defined, including radiotherapy in extended field (EF) or involved field (IF) technique, combined modality treatment, and, more recently, monoclonal antibody rituximab. Watch and wait strategy plays an important role in pediatric oncology to avoid adverse effects associated with therapy.
Cyclic stretch activates ERK1/2 via G proteins and EGFR in alveolar epithelial cells (2002)

Mechanical stimuli are transduced into intracellular signals in lung alveolar epithelial cells (AEC). We studied whether mitogen-activated protein kinase (MAPK) pathways are activated during cyclic stretch of AEC. Cyclic stretch induced a rapid (within 5 min) increase in extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation in AEC. The inhibition of Na(+), L-type Ca(2+) and stretch-activated ion channels with amiloride, nifedipine, and gadolinium did not prevent the stretch-induced ERK1/2 activation. The inhibition of Grb2-SOS interaction with an SH3 binding sequence peptide, Ras with a farnesyl transferase inhibitor, and Raf-1 with forskolin did not affect the stretch-induced ERK1/2 phosphorylation. Moreover, cyclic stretch did not increase Ras activity, suggesting that stretch-induced ERK1/2 activation is independent of the classical receptor tyrosine kinase-MAPK pathway. Pertussis toxin and two specific epidermal growth factor receptor (EGFR) inhibitors (AG-1478 and PD-153035) prevented the stretch-induced ERK1/2 activation. Accordingly, in primary AEC, cyclic stretch activates ERK1/2 via G proteins and EGFR, in Na(+) and Ca(2+) influxes and Grb2-SOS-, Ras-, and Raf-1-independent pathways.
Physicochemical basis for the rapid time‐action of LysB28ProB29‐insulin: Dissociation of a protein‐ligand complex (1996)

The rate-limiting step for the absorption of insulin solutions after subcutaneous injection is considered to be the dissociation of self-associated hexamers to monomers. To accelerate this absorption process, insulin analogues have been designed that possess full biological activity and yet have greatly diminished tendencies to self-associate. Sedimentation velocity and static light scattering results show that the presence of zinc and phenolic ligands (m-cresol and/or phenol) cause one such insulin analogue, LysB28ProB29-human insulin (LysPro), to associate into a hexameric complex. Most importantly, this ligand-bound hexamer retains its rapid-acting pharmacokinetics and pharmacodynamics. The dissociation of the stabilized hexameric analogue has been studied in vitro using static light scattering as well as in vivo using a female pig pharmacodynamic model. Retention of rapid time-action is hypothesized to be due to altered subunit packing within the hexamer. Evidence for modified monomer-monomer interactions has been observed in the X-ray crystal structure of a zinc LysPro hexamer (Ciszak E et al., 1995, Structure 3:615-622). The solution state behavior of LysPro, reported here, has been interpreted with respect to the crystal structure results. In addition, the phenolic ligand binding differences between LysPro and insulin have been compared using isothermal titrating calorimetry and visible absorption spectroscopy of cobalt-containing hexamers. These studies establish that rapid-acting insulin analogues of this type can be stabilized in solution via the formation of hexamer complexes with altered dissociation properties.
High temperature operation with low-loss couplingto fibrefor narrow-beam 1.3 µm laserswith butt-jointed selective grown spot-size converter (1995)

High temperature operation is demonstrated for narrow-beam 1.3 µm lasers with butt-jointed selectively grown spot-size converters. Low thresholds of 5.6 mA and 15.8 mA at 25°C and 85°C and a maximum operating temperature of 134°C were obtained. Low loss coupling to fibre of &lt;1.8 dB was achieved in the temperature range from 25°C to 85°C with an output power up to 30 mW.
O -GlcNAc modification in diabetes and Alzheimer's disease (2007)

Abstract Similar to phosphorylation, O-GlcNAcylation (or simply GlcNAcylation) is an abundant, dynamic, and inducible post-translational modification. In some cases, GlcNAcylation and phosphorylation occur at the same or adjacent sites, modulating each other. GlcNAcylated proteins are crucial in regulating virtually all cellular processes, including signaling, cell cycle, and transcription, among others. GlcNAcylation affects protein–protein interactions, activity, stability, and expression. Several GlcNAcylated proteins are involved in diabetes and Alzheimer's disease. Hyperglycemia increases GlcNAcylation of proteins within the insulin signaling pathway and contributes to insulin resistance. In addition, hyperinsulinemia and hyperlipidemia are also associated with increased GlcNAcylation, which affect and regulate several insulin signaling proteins, as well as proteins involved on the pathology of diabetes. With respect to Alzheimer's disease, several proteins involved in the etiology of the disease, including tau, neurofilaments, beta-amyloid precursor protein, and synaptosomal proteins are GlcNAcylated in normal brain. The impairment of brain glucose uptake/metabolism is a known metabolic defect in Alzheimer's neurons. Data support the hypothesis that hypoglycemia within the brain may reduce the normal GlcNAcylation of tau, exposing kinase acceptor sites, thus leading to hyperphosphorylation, which induces tangle formation and neuronal death. Alzheimer's disease and type II diabetes represent two metabolic disorders where dysfunctional protein GlcNAcylation/phosphorylation may be important for disease pathology.
Co-utilization of L-arabinose and D-xylose by laboratory and industrial Saccharomyces cerevisiae strains (2006)

Our work demonstrates simultaneous co-utilization of xylose and arabinose in recombinant strains of S. cerevisiae. In addition, the co-utilization of arabinose together with xylose significantly reduced formation of the by-product xylitol, which contributed to improved ethanol production.