gebhart/patrepeval huggingface dataset:
Notch Inhibition of E47 Supports the Existence of a Novel Signaling Pathway (1998)

E47 is a widely expressed transcription factor that activates B-cell-specific immunoglobulin gene transcription and is required for early B-cell development. In an effort to identify processes that regulate E47, and potentially B-cell development, we found that activated Notch1 and Notch2 effectively inhibit E47 activity. Only the intact E47 protein was inhibited by Notch-fusion proteins containing isolated DNA binding and activation domains were unaffected-suggesting that Notch targets an atypical E47 cofactor. Although overexpression of the coactivator p300 partially reversed E47 inhibition, results of several assays indicated that p300/CBP is not a general target of Notch. Notch inhibition of E47 did not correlate with its ability to activate CBF1/RBP-Jkappa, the mammalian homolog of Suppressor of Hairless, a protein that associates physically with Notch and defines the only known Notch signaling pathway in drosophila. Importantly, E47 was inhibited independently of CBF1/RPB-Jkappa by Deltex, a second Notch-interacting protein. We provide evidence that Notch and Deltex may act on E47 by inhibiting signaling through Ras because (i) full E47 activity was found to be dependent on Ras and (ii) both Notch and Deltex inhibited GAL4-Jun, a hybrid transcription factor whose activity is dependent on signaling from Ras to SAPK/JNK.
Prostaglandin Receptor Signaling in Disease (2007)

Prostanoids, consisting of the prostaglandins (PGs) and the thromboxanes (TXs), are a group of lipid mediators formed in response to various stimuli. They include PGD2, PGE2, PGF2alpha, PGI2, and TXA2. They are released outside of the cells immediately after synthesis, and exert their actions by binding to a G-protein coupled rhodopsin-type receptor on the surface of target cells. There are eight types of the prostanoid receptors conserved in mammals from mouse to human. They are the PGD receptor (DP), four subtypes of the PGE receptor (EP1, EP2, EP3, and EP4), the PGF receptor (FP), PGI receptor (IP), and TXA receptor (TP). Recently, mice deficient in each of these prostanoid receptors were generated and subjected to various experimental models of disease. These studies have revealed the roles of PG receptor signaling in various pathological conditions, and suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of the pathological conditions. Here we review these recent findings of roles of prostanoid receptor signaling and their therapeutic implications.
Human immunodeficiency virus type 1 nucleocapsid protein specifically stimulates Mg2+-dependent DNA integration in vitro (1997)

The integrase (IN) protein of the human immunodeficiency virus mediates integration of the viral DNA into the cellular genome. In vitro, this reaction can be mimicked by using purified recombinant IN and model DNA substrates. IN mediates two reactions: an endonucleolytic cleavage at each 3' end of the proviral DNA (terminal cleavage) and the joining of the linear viral DNA to 5' phosphates in the target DNA (strand transfer). Previous investigators have shown that purified IN requires Mn2+ or Mg2+ to promote strand transfer in vitro, although Mg2+ is the likely metal cofactor in vivo. IN activity in the presence of Mg2+ in vitro requires high IN concentrations and low concentrations of salt. Here, we show that the viral nucleocapsid protein NCp7 allows efficient IN-mediated strand transfer in the presence of Mg2+ at low enzyme concentrations. This potentiating effect appears to be unique to NCp7, as other small DNA-binding proteins, while capable of stimulating integration in the presence of Mn2+, all failed to stimulate strand transfer in the presence of Mg2+.
Structure of peptostreptococcal protein L and identification of a repeated immunoglobulin light chain-binding domain. (1992)

The gene for protein L, an immunoglobulin (Ig) light chain-binding protein expressed by some strains of the anaerobic bacterial species Peptostreptococcus magnus, was cloned and sequenced. The gene translates into a protein of 719 amino acid residues. Following a signal sequence of 18 amino acids and a NH2-terminal region ("A") of 79 residues, the molecule contains five homologous "B" repeats of 72-76 amino acids each. Further, toward the COOH terminus, two additional repeats ("C") were found. These are not related to the "B" repeats, but are highly homologous to each other. After the C repeats (52 amino acids each), a hydrophilic, proline-rich putative cell wall-spanning region ("W") was found, followed at the COOH-terminal end by a hydrophobic membrane anchor ("M"). Fragments of the gene were expressed, and the corresponding peptides were analyzed for Ig-binding activity. The B repeats were found to be responsible for the interaction with Ig light chains. An Escherichia coli high level expression system was adapted for the production of large amounts of two Ig-binding protein L fragments comprising one and four B repeats, respectively.
Unternehmerischer Handlungsspielraum des Vorstandes zwischen zivilrechtlicher Verantwortung und strafrechtlicher Sanktion (2009)

Unternehmerischer Handlungsspielraum des Vorstandes zwischen zivilrechtlicher Verantwortung und strafrechtlicher Sanktion
Transparent Slippery Surfaces Made with Sustainable Porous Cellulose Lauroyl Ester Films (2014)

In recent years, liquid repellent surfaces have attracted considerable attention because of their wide array of potential applications. In the present study, slippery surfaces were fabricated using novel sustainable, nanoporous cellulose lauroyl ester (CLE) films and slippery lubrication fluid. The nanoporous CLE films were obtained after spray-coating target surfaces using a nanoparticle suspension of CLE that was prepared via nanoprecipitation. After the deposition of the slippery liquid within the porous network, the obtained slippery surfaces exhibit both excellent liquid repellency upon liquid impact and anti-icing properties (by significantly retarding the icing time). Three-dimensional droplet manipulation was also achieved on these surfaces by taking advantage of the materials' low contact angle hysteresis and low adhesion property.
Modulation of Respiratory System by Limb Muscle Afferents in Intact and Injured Spinal Cord (2019)

Breathing constantly adapts to environmental, metabolic or behavioral changes by responding to different sensory information, including afferent feedback from muscles. Importantly, not just respiratory muscle feedback influences respiratory activity. Afferent sensory information from rhythmically moving limbs has also been shown to play an essential role in the breathing. The present review will discuss the neuronal mechanisms of respiratory modulation by activation of peripheral muscles that usually occurs during locomotion or exercise. An understanding of these mechanisms and finding the most effective approaches to regulate respiratory motor output by stimulation of limb muscles could be extremely beneficial for people with respiratory dysfunctions. Specific attention in the present review is given to the muscle stimulation to treat respiratory deficits following cervical spinal cord injury.
Effects of immunoglobulin structure on Fc receptor binding: a mouse myeloma variant immunoglobulin with a gamma 2b-gamma 2a hybrid heavy chain having a complete gamma 2a Fc region fails to bind to gamma 2a Fc receptors on mouse macrophages. (1982)

We report here the primary structure of an immunoglobulin heavy chain synthesized by ICR 16, a variant of the MPC 11 mouse myeloma cell line. The ICR 16 heavy chain is a gamma 2b-gamma 2a hybrid, consisting of the CH1 domain of gamma 2b and the hinge, CH2 and CH3 domains of gamma 2a subclasses. The genetic mechanism by which ICR 16 occurred may be recombination, based on homologies in both coding and intervening sequences in gamma 2b and gamma 2a constant region genes. Although the Fc fragment of ICR 16 is completely gamma 2a-like and has been shown to bind to gamma 2a Fc receptors on mouse macrophages, the intact H2L2 molecules is unable to do so. Such an observation underscores the crucial role that conformation may play in the ability of immunoglobulins to carry out biologic functions.
Enhancement of wound repair with a topically applied nitric oxide‐releasing polymer (1996)

Nitric oxide is an important cytotoxic agent for host defense which also regulates gene expression, signal transduction, and vasodilation. In normal wounds, nitric oxide synthesis and metabolism are significantly increased during inflammation and tissue remodeling. However, nitric oxide production is suppressed in wounds where healing is impaired by diabetes or steroid-treatment. Topical delivery of nitric oxide in therapeutic amounts may alleviate this deficiency and thereby enhance wound repair. Consequently, we developed polyethyleneimine cellulose NONOate polymer, a nonsoluble, nontoxic, polymer-based NONOate--one of a new class of compounds that spontaneously release nitric oxide in a controlled fashion in aqueous media. Polyethyleneimine cellulose NONOate polymer was synthesized from polyethyleneimine cellulose to provide extended nitric oxide release with a half-life of 16 hours. Polyethyleneimine cellulose NONOate polymer or a control polymer was applied topically on full-thickness dermal wounds of rats at the time of wounding and days 3, 7, 10, 14, 17, and 21. Nitric oxide delivery was determined indirectly by measuring urinary nitrate. The first two polyethyleneimine cellulose NONOate polymer applications increased urinary nitrate output twofold to fourfold, whereas urinary nitrate output of control rats did not significantly increase. Nitrate output in polyethyleneimine cellulose NONOate polymer-treated rats was elevated compared with controls after each application, although this was attenuated in later applications. Rate of wound closure was measured with computer-based video imaging. Polyethyleneimine cellulose NONOate polymer-treated wounds were significantly smaller (p < 0.05) on days 7, 10, and 17 relative to controls, based on percentage of wound open relative to initial wound area. In a second experiment, telemetry-implanted rats were wounded to detect potential hypotensive effects as a result of polyethyleneimine cellulose NONOate polymer application. Topical polyethyleneimine cellulose NONOate polymer application to wounds showed no prolonged hypotensive effects, in contrast to a soluble NONOate which suppressed systolic blood pressure for over 6 hours. These results show that a nonsoluble, polymeric NONOate can provide topical nitric oxide delivery to wounds in a controlled manner, which may enhance wound healing. Further studies are in progress with other promising NONOate candidates to establish dose-response effects and therapeutic limits of exogenous nitric oxide release in impaired wound models.
Subjective health status in men and women with congenital adrenal hyperplasia: a population-based survey in Norway (2010)

In this population-based survey of patients with classical CAH, we found that subjective health status and working ability were impaired, and that fertility was reduced in females. There is a need for improvement of the medical treatment and the general care of this patient group.
Dyrk kinases regulate phosphorylation of doublecortin, cytoskeletal organization, and neuronal morphology (2012)

In a neuronal overexpression screen focused on kinases and phosphatases, one "hit" was the dual specificity tyrosine phosphorylation-regulated kinase (Dyrk4), which increased the number of dendritic branches in hippocampal neurons. Overexpression of various Dyrk family members in primary neurons significantly changed neuronal morphology. Dyrk1A decreased axon growth, Dyrk3 and Dyrk4 increased dendritic branching, and Dyrk2 decreased both axon and dendrite growth and branching. Kinase-deficient mutants revealed that most of these effects depend on kinase activity. Because doublecortin (DCX), a microtubule-binding protein, regulates cytoskeletal dynamics and neuronal morphogenesis, we investigated the possibility that DCX is a target of Dyrks. We found that overexpression of Dyrk2 and Dyrk3, but not Dyrk1A or Dyrk4, can change DCX phosphorylation status. Mutation of a consensus phosphorylation site for Dyrk kinases at Serine 306 (Ser306) in DCX indicated that this is one target site for Dyrk2 and Dyrk3. Overexpression of Dyrk2 restored altered DCX distribution in the growth cones of dendrites and axons, and partially reversed the morphological effects of DCX overexpression; some of these effects were abrogated by mutation of Ser306 to alanine. These studies implicate Dyrks in the regulation of cytoskeletal organization and process outgrowth in neurons, and suggest that DCX is one relevant Dyrk target.
Death Don't Have No Mercy: Cell Death Programs in Plant-Microbe Interactions. (1996)

A nearly ubiquitous feature of plant-pathogen is host cell death. In its most recognizable form, host cell death is manifested as the rapid collapse of tissue, termed the hypersensitive response (HR). This response accompanies interactions and leads to disease resistance. As detailed below, the HR is programmed genetically in the plant and is a consequence of new host transcription and trans? lation (Dixon et al., 1994; Godiard et al., 1994). The HR is a correlative feature of many but not all incompatible interac? tions controlled by classic disease resistance (R) genes (Dangl, 1995; Staskawicz et al., 1995; see also Bent, 1996, in this is? sue). A local HR is often associated with the onset of systemic acquired resistance (SAR; Chester, 1933; Enyedi et al., 1992; Ryals et al., 1994, 1996, in this issue) in distal plant tissues. In addition, sites of the HR are invariably focal points for tran? scriptional induction of plant defense genes in neighboring cells (Somssich et al., 1988; Schmelzer et al., 1989). Subse? quent biosynthesis of protective secondary metabolites and cell wall buttressing around the HR site are also thought to contribute to overall pathogen containment. Signals derived from cells undergoing the HR apparently contribute signifi? cantly to the induction of defense gene transcription in adjacent cells. However, certain bacterial mutants unable to elicit an HR are still competent to trigger the transcription of defense genes that are normally induced during both incompatible and compatible (Jakobek and Lindgren, 1993). Whether the cell death that constitutes the HR actually causes disease resistance by depriving the incoming patho? gen of nutrients or by releasing microbiocidal compounds from dying cells is unclear. Alternatively, the HR could be the con? sequence of a mechanism that is actually killing both host and microbe cells. In fact, recent evidence discussed below sug? gests that HR cell death is not required to stop pathogen growth in at least some cases (Century et al., 1995; Hammond-Kosack et al., 1996). If this separation of resistance per se and cell death is generalizable, can we glean insight from the mecha? nism by which host cells die that is relevant to the mechanism that kills or stops an invading pathogen?
Expansion of circulating T cells resembling follicular helper T cells is a fixed phenotype that identifies a subset of severe systemic lupus erythematosus (2009)

These findings in SLE patients are consistent with the autoimmune mechanism in sanroque mice and identify Tfh effector molecules as possible therapeutic targets in a recognizable subset of patients with SLE.
Multiplexed Nanoflares: mRNA Detection in Live Cells (2012)

We report the development of the multiplexed nanoflare, a nanoparticle agent that is capable of simultaneously detecting two distinct mRNA targets inside a living cell. These probes are spherical nucleic acid (SNA) gold nanoparticle (Au NP) conjugates consisting of densely packed and highly oriented oligonucleotide sequences, many of which are hybridized to a reporter with a distinct fluorophore label and each complementary to its corresponding mRNA target. When multiplexed nanoflares are exposed to their targets, they provide a sequence specific signal in both extra- and intracellular environments. Importantly, one of the targets can be used as an internal control, improving detection by accounting for cell-to-cell variations in nanoparticle uptake and background. Compared to single-component nanoflares, these structures allow one to determine more precisely relative mRNA levels in individual cells, improving cell sorting and quantification.
An Engineered GM-CSF-CCL2 Fusokine Is a Potent Inhibitor of CCR2-Driven Inflammation As Demonstrated in a Murine Model of Inflammatory Arthritis (2009)

CCR2 is a chemokine receptor widely expressed by lymphomyeloid cells involved in maladaptive autoimmune ailments. Therefore CCR2 is of great interest as a biological target for immune suppression due to its direct implication in autoimmune diseases such as rheumatoid arthritis. We have generated a novel fusion protein using GM-CSF and an N-terminal truncated version of MCP-1/CCL2 (6-76, GMME1) and investigated its utility as a CCR2-specific immune suppressor. Using BRET studies, we found that distinct to CCL2, GMME1 binding to CCR2 led to altered conformational changes in the CCR2 homodimer and did not induce the recruitment of beta-arrestin 2 to the receptor. However, CCR2-dependent calcium mobilization, BAX induction and caspase-3 activation followed by cell death was observed. Using Th17 cells harvested from DBA/1 mice ill with bovine collagen-induced arthritis, we demonstrate that GMME1 is capable of blocking their production of IL-17 in vitro. Upon its delivery to mice symptomatic with inflammatory arthritis, a robust clinical recovery occurred with decreased paw thickness to normal levels and a significant reduction in anti-collagen Ab titer and rheumatoid factor titer, as well as reduction of proinflammatory cytokines levels both intraarticular and systemic. Our data demonstrate that GMME1 is a powerful synthetic suppressor cytokine that coopts CCR2-dependent cellular signaling and blunts the effects of CCR2-expressing lymphomyeloid cells causative of autoimmune arthritis.
Dietary Fiber, Weight Gain, and Cardiovascular Disease Risk Factors in Young Adults (1999)

Fiber consumption predicted insulin levels, weight gain, and other CVD risk factors more strongly than did total or saturated fat consumption. High-fiber diets may protect against obesity and CVD by lowering insulin levels.
Bassweight (2012)

Despite the advent of digital recording devices of every size and shape (read: camera phones), there have been not nearly enough attempts to adequately document in brilliant photography and text the electronic festival underground along the West Coast of North America. Though Burning Man is quite possibly one of the world's largest if not most significant gatherings of freak culture and various media abound that render spectacular its participants, there are few attempts to portray such electronicultures in a thoughtful and insightful form. The same can be said for documentation of similar festivals up and down the left coast, from Shambhala in BC to Faerie Worlds in Oregon and Harmony Festival in Northern California. With Tribal Revival, something of this archival mission has succeeded, with 200 pages of colour photography documenting several years of festival culture and expression from the West Coast, circa 2002 through 2009.
The l-Arginine (1991)

Summary: Nitric oxide (NO) is synthesized from l-arginine by an enzyme called the NO synthase. NO production by vascular endothelial cells accounts for the biological properties of endothelium-derived relaxing factor and maintains a vasodilator tone. Platelets also produce NO, which modulates their aggregability. In the central nervous system NO mediates the effects of excitatory amino acids. In all these tissues the l-arginine:NO pathway acts as a transduction mechanism for the soluble guanylate cyclase, for which NO is the endogenous stimulator. NO is also released after immunological stimulation in macrophages, neutrophils, and other cells. NO thus released acts as part of the host defense mechanism, for it is cytotoxic or cytostatic for tumor cells and invasive organisms and may mediate other aspects of the immunological response. Discovery of the l-arginine:NO pathway has far reaching implications for the understanding of several areas in biology and indicates potential novel therapies for a number of diseases.
A Universal, Photocleavable DNA Base:  Nitropiperonyl 2‘-Deoxyriboside (2001)

A universal, photochemically cleavable DNA base analogue would add desirable versatility to a number of methods in molecular biology. A novel C-nucleoside, nitropiperonyl deoxyriboside (NPdR, P), has been investigated for this purpose. NPdR can be converted to its 5'-DMTr-3'-CE-phosphoramidite and was incorporated into pentacosanucleotides by conventional synthesis techniques. The destabilizing effect on hybrid formation with a complementary strand when this P base opposes A, T, and G was found to be 3-5 kcal/mol, but 9 kcal/mol when it opposes C. Brief irradiation (lambda > 360 nm, 20 min) of DNA containing the P base and piperidine treatment causes strand cleavage giving the 3'- and 5'-phosphates. Two significant recent interests, universal/non-hydrogen-bonding base analogues and photochemical backbone cleavage, have thus been combined in a single molecule that serves as a light-based DNA scissors.
Hepatic maturation in differentiating embryonic stem cells in vitro (2001)

We investigated the potential of mouse embryonic stem (ES) cells to differentiate into hepatocytes in vitro. Differentiating ES cells expressed endodermal‐specific genes, such as α‐fetoprotein, transthyretin, α 1‐anti‐trypsin and albumin, when cultured without additional growth factors and late differential markers of hepatic development, such as tyrosine aminotransferase (TAT) and glucose‐6‐phosphatase (G6P), when cultured in the presence of growth factors critical for late embryonic liver development. Further, induction of TAT and G6P expression was induced regardless of expression of the functional SEK1 gene, which is thought to provide a survival signal for hepatocytes during an early stage of liver morphogenesis. The data indicate that the in vitro ES differentiation system has a potential to generate mature hepatocytes. The system has also been found useful in analyzing the role of growth factors and intracellular signaling molecules in hepatic development.