gebhart/patrepeval huggingface dataset:
A new pathway for the secretion of virulence factors by bacteria: The flagellar export apparatus functions as a protein-secretion system (1999)

Biogenesis of the flagellum, a motive organelle of many bacterial species, is best understood for members of the Enterobacteriaceae. The flagellum is a heterooligomeric structure that protrudes from the surface of the cell. Its assembly initially involves the synthesis of a dedicated protein export apparatus that subsequently transports other flagellar proteins by a type III mechanism from the cytoplasm to the outer surface of the cell, where oligomerization occurs. In this study, the flagellum export apparatus was shown to function also as a secretion system for the transport of several extracellular proteins in the pathogenic bacterium Yersinia enterocolitica. One of the proteins exported by the flagellar secretion system was the virulence-associated phospholipase, YplA. These results suggest type III protein secretion by the flagellar system may be a general mechanism for the transport of proteins that influence bacterial-host interactions.
Communications in NBC Television Central (1976)

Improved communications for NBC's entire New York plant was a major goal of the recent NBC Television Central project. Throughout the planning, design, and installation phases, the operating modes of the existing communications subsystems provided a baseline for technical and operational improvements. Among subsystems discussed in this paper are production interphone, interrupted-return-feed, engineering interphone, and intercom. Also discussed are specific problems of telephone interfacing, telecine and videotape machine communications, and communication with remote areas.
The Structure-Specific Endonuclease Ercc1-Xpf Is Required To Resolve DNA Interstrand Cross-Link-Induced Double-Strand Breaks (2004)

Interstrand cross-links (ICLs) are an extremely toxic class of DNA damage incurred during normal metabolism or cancer chemotherapy. ICLs covalently tether both strands of duplex DNA, preventing the strand unwinding that is essential for polymerase access. The mechanism of ICL repair in mammalian cells is poorly understood. However, genetic data implicate the Ercc1-Xpf endonuclease and proteins required for homologous recombination-mediated double-strand break (DSB) repair. To examine the role of Ercc1-Xpf in ICL repair, we monitored the phosphorylation of histone variant H2AX (gamma-H2AX). The phosphoprotein accumulates at DSBs, forming foci that can be detected by immunostaining. Treatment of wild-type cells with mitomycin C (MMC) induced gamma-H2AX foci and increased the amount of DSBs detected by pulsed-field gel electrophoresis. Surprisingly, gamma-H2AX foci were also induced in Ercc1(-/-) cells by MMC treatment. Thus, DSBs occur after cross-link damage via an Ercc1-independent mechanism. Instead, ICL-induced DSB formation required cell cycle progression into S phase, suggesting that DSBs are an intermediate of ICL repair that form during DNA replication. In Ercc1(-/-) cells, MMC-induced gamma-H2AX foci persisted at least 48 h longer than in wild-type cells, demonstrating that Ercc1 is required for the resolution of cross-link-induced DSBs. MMC triggered sister chromatid exchanges in wild-type cells but chromatid fusions in Ercc1(-/-) and Xpf mutant cells, indicating that in their absence, repair of DSBs is prevented. Collectively, these data support a role for Ercc1-Xpf in processing ICL-induced DSBs so that these cytotoxic intermediates can be repaired by homologous recombination.
Mechanisms of Feeding Efficiency in Preterm Infants (1986)

Nutritive sucking was studied in 18 preterm infants. Differences in feeding efficiency could not be explained by differences in sucking rate. Quick efficient drinking, however, was characterized by long sucking bursts and by a large amount of milk intake during each sucking movement. Slow inefficient drinking was characterized by short sucking bursts and by a small amount of milk intake during each sucking movement.
Correspondence of the Functional Epitopes of Poxvirus and Human Interleukin-18-Binding Proteins (2001)

Molluscum contagiosum virus, a human poxvirus that causes persistent small benign skin tumors, encodes a variety of putative immune defense proteins. Three such proteins, MC51L, MC53L, and MC54L, have 20 to 35% amino acid sequence identities with human interleukin-18 (hIL-18)-binding protein (hIL-18BP), a naturally occurring antagonist of the proinflammatory cytokine IL-18. We previously demonstrated that seven amino acids within the immunoglobulin-like domain of hIL-18BP were important for high-affinity binding to hIL-18. Model building indicated that MC54L, which has been shown to bind hIL-18, contains five of the seven amino acids at corresponding positions in its immunoglobulin-like domain, the exceptions being the conservative substitution of isoleucine for a leucine and the nonconservative substitution of valine for a phenylalanine. We found that individual alanine substitutions for these six identical or highly conserved amino acids of MC54L caused changes in affinity and binding free energy for hIL-18 that were quantitatively similar to those produced by mutagenesis of hIL-18BP. Furthermore, when the nonconserved valine of MC54L was mutated to phenylalanine, making it more like hIL-18BP, its affinity for hIL-18 increased more than 10-fold. In addition, the carboxyl-terminal half of MC54L, which has no similarity with hIL-18BP, was dispensable for hIL-18 binding. Thus, despite their relatively low overall sequence identity, MC54L and hIL-18BP have similar hIL-18 binding sites and functional epitopes. On the other hand, MC51L and MC53L have nonconservative substitutions of three to six of the seven critical amino acids of hIL-18BP and neither protein bound hIL-18, suggesting that they may interact with unidentified ligands.
Water-soluble polysaccharide-anthracycline conjugates: biological activity. (1992)

The anticancer agents doxorubicin and daunorubicin were covalently linked to the water-soluble anionic polysaccharides hyaluronic acid and carboxy-methylcellulose. The drug-polymer conjugates are in principle prevented from entering cells, can efficiently bind to cell surfaces and allow precise dose-response determinations. In addition, they are not able to bind DNA because of their negative charge. Cell growth and DNA synthesis inhibition studies indicated decreased cell toxicity for the polymer conjugates. The mol. wt of the carrier was shown to affect the biological activity of the anthracycline to a moderate extent. Partial drug incorporation into cells was observed as a function of time, probably due to endocytosis phenomena followed by biochemical cleavage of the conjugate. The conclusion was drawn that membrane binding appears to contribute to total toxicity only to a minor extent.
Control and host‐dependent activation of insect toxin expression in a root‐associated biocontrol pseudomonad (2012)

Pseudomonas fluorescens CHA0 is a root-associated biocontrol agent that suppresses soil-borne fungal diseases of crops. Remarkably, the pseudomonad is also endowed with systemic and oral activity against pest insects which depends on the production of the insecticidal Fit toxin. The toxin gene (fitD) is part of a virulence cassette encoding three regulators (FitF, FitG, FitH) and a type I secretion system (FitABC-E). Immunoassays with a toxin-specific antibody and transcriptional analyses involving fitG and fitH deletion and overexpression mutants identified LysR family regulator FitG and response regulator FitH as activator and repressor, respectively, of Fit toxin and transporter expression. To visualize and quantify toxin expression in single live cells by fluorescence microscopy, we developed reporters which in lieu of the native toxin protein express a fusion of the Fit toxin with red fluorescent mCherry. In a wild-type background, expression of the mCherry-tagged Fit toxin was activated at high levels in insect hosts, i.e. when needed, yet not on plant roots or in batch culture. By contrast, a derepressed fitH mutant expressed the toxin in all conditions. P. fluorescens hence can actively induce insect toxin production in response to the host environment, and FitH and FitG are key regulators in this mechanism.
Current Concepts Review - Cellular Biology of Bone-Resorbing Cells* (1996)

Resorption of bone occurs continuously throughout life, first as part of skeletal growth and modeling and, later, in the process of bone-remodeling in the adult skeleton. Since the 1970's, considerable progress has been made in unraveling the basic cellular mechanisms that regulate the formation and activity of the osteoclast, the main cellular agent of bone resorption. These recent advances have resulted mainly from the introduction of new methods of isolation and culture of osteoclasts and evaluation of resorptive activity; techniques have also been developed for the generation of osteoclasts in long-term culture of precursor cells found in hematopoietic tissues and peripheral blood. Although reports have suggested that other cells (such as tumor cells or macrophages) are capable of degrading bone matrix48,104,152 and releasing local factors that contribute to resorption of bone45,102,105,113, the osteoclast is the only cell specialized for this function.

The purpose of this review is to integrate new knowledge regarding the formation of osteoclasts and the regulation of their activity within a general view of the cellular biology of normal and pathological bone resorption. After a review of the criteria by which osteoclastic cells are defined, the origin and formation of osteoclasts will be considered, along with mechanisms governing their recruitment, activation, and function. The manner in which these mechanisms contribute to osteoclastic bone resorption under various pathological conditions as well as the possible roles of other cells (both skeletal and extraskeletal in origin) in this process will be discussed.

Studies on the biology of bone-resorbing cells can be properly evaluated only if the criteria for the recognition of osteoclasts are clearly defined. On histological sections, osteoclasts are readily identified as large multinucleated cells that lie in apposition to a bone surface undergoing lacunar resorption …
Receptor tyrosine kinases (1992)

A major process through which environmental information is transmitted into cells is via activation of protein tyrosine kinases. Receptor tyrosine kinases contain extracellular ligand recognition, single membrane spanning, and cytoplasmic protein tyrosine kinase domains. The cytoplasmic kinase core is flanked by regulatory segments, which in some family members are also inserted into the core kinase domain. Ligand binding initiates receptor signaling from the cell surface. Activated receptors autophosphorylate to remove alternate substrate/inhibitory constraints and to provide loci for assembly of proteins that contain SRC homology regions. Information is transmitted and diffused by tyrosine phosphorylation of the assembled proteins and of cellular substrates that include protein kinases with specificity for serine/threonine residues. Signaling, which is strictly ligand-dependent, is attenuated by down-regulation of receptors and by feed-back inhibitory loops that involve receptor phosphorylation by cellular kinases. The tyrosine kinase receptors are essential for normal growth, development, and reparative processes. Mutations that remove normal regulatory constraints on the approximately 290 amino acid kinase core of these large proteins result in constitutive function and cell transformation.
Antibody against leukocyte integrin (CD18) prevents reperfusion-induced lung vascular injury (1990)

We studied the effects of pretreatment of rabbits with a monoclonal antibody (MoAb) IB4 directed against an epitope on the common beta-chain of leukocyte adhesion glycoprotein CD18 on the development of pulmonary edema following pulmonary artery occlusion and reperfusion. A balloon catheter occluded the right pulmonary artery in rabbits for 24 h, and the balloon was then deflated to allow reperfusion for 2 h. The lungs were removed, attached to a weighing balance, and perfused with Ringer-albumin solution (0.5 g/100 ml). IB4 (0.5 mg/kg) was infused 45 min before the start of reperfusion. In another experiment, we infused OKM-1 (0.5 mg/kg), a control MoAb directed against an irrelevant epitope on the alpha-chain of CD11b/CD18. IB4 prevented rabbit neutrophil adherence to pulmonary artery endothelial cells in vitro in response to a variety of stimuli, whereas OKM-1 was ineffective. Pulmonary artery occlusion and reperfusion increased the lung myeloperoxidase (MPO) content, whereas IB4 prevented the increase in MPO content. The increase in lung weight in the IB4-treated group (400 +/- 40 mg from baseline) was less (P less than 0.001) than in the untreated control group (1,400 +/- 90 mg) and the OKM-1-treated control group (1,320 +/- 125 mg). IB4 pretreatment also prevented the increase in pulmonary capillary filtration coefficient (a measure of capillary permeability to water) occurring in control and OKM-1-treated groups. The results indicate that neutrophil sequestration in the pulmonary microcirculation mediated by CD18 glycoprotein is a major determinant of reperfusion-induced lung vascular injury.
Human myeloid cells express an activating ILT receptor (ILT1) that associates with Fc receptor gamma-chain. (1999)

Ig-like transcripts (ILTs) encode cell surface receptors expressed on myeloid and lymphoid cells that are structurally and functionally related to killer cell inhibitory receptors. One ILT, designated ILT1, contains a short cytoplasmic domain that lacks sequence motifs implicated in signal transduction. Its function is unknown. Similar short cytoplasmic domains have been observed in activating NK cell receptors and FcalphaR, which transduce stimulatory signals via associated DAP12 and FcepsilonRIgamma proteins, respectively. Here we show that ILT1 receptor is selectively expressed on myeloid cells, functions as an activating receptor, and associates with FcepsilonRIgamma rather than DAP12.
Aluminum Exposure From Pediatric Parenteral Nutrition: Meeting the New FDA Regulation (2008)

Background: Aluminum toxicity can cause serious central nervous system and bone toxicities. Aluminum is a contaminant of parenteral nutrition (PN) solution components. Premature neonates requiring high doses of calcium and phosphate to mineralize their bones, children with impaired renal function, and children on PN therapy for prolonged duration are at the highest risk. Effective in July 2004, the U.S. Food and Drug Administration (FDA) mandated labeling requirements for aluminum content in all PN solution components. To assess the aluminum exposure in neonatal and pediatric populations, this study aims to determine patients' daily aluminum load (μg/kg/d) delivered from PN solutions. Methods: The study included all inpatients who received PN during calendar year 2006 (13,384 PN patient days). The calculated parameters of μg/kg/d and μg/L of parentally administered aluminum were stratified according to patient age and weight. Aluminum content by product and manufacturer were tabulated. Results: Forty‐nine percent of the PN patient days were in patients weighing &lt; 3 kg. These patients also received the largest amounts of aluminum (range, 30‐60μ g/kg/d). Meeting the FDA regulation was possible only in patients weighing&gt; 50 kg. Conclusions: Currently available parenteral products used to make PN solutions contain amounts of aluminum that make it impossible to meet the new FDA rule of &lt;5 μg/kg/d of aluminum exposure. Manufacturers must identify, develop, and adopt new methods to reduce the aluminum contamination in their products. Health care professionals should calculate aluminum loads in patients and make informed decisions when choosing PN products.
MECHANISMS OF HELICASE-CATALYZED DNA UNWINDING (1996)

DNA helicases are essential motor proteins that function to unwind duplex DNA to yield the transient single-stranded DNA intermediates required for replication, recombination, and repair. These enzymes unwind duplex DNA and translocate along DNA in reactions that are coupled to the binding and hydrolysis of 5'-nucleoside triphosphates (NTP). Although these enzymes are essential for DNA metabolism, the molecular details of their mechanisms are only beginning to emerge. This review discusses mechanistic aspects of helicase-catalyzed DNA unwinding and translocation with a focus on energetic (thermodynamic), kinetic, and structural studies of the few DNA helicases for which such information is available. Recent studies of DNA and NTP binding and DNA unwinding by the Escherichia coli (E. coli) Rep helicase suggest that the Rep helicase dimer unwinds DNA by an active, rolling mechanism. In fact, DNA helicases appear to be generally oligomeric (usually dimers or hexamers), which provides the helicase with multiple DNA binding sites. The apparent mechanistic similarities and differences among these DNA helicases are discussed.
Chemical Microstructure of Cortical Bone Probed by Raman Transects (1999)

Raman transects, microspectra taken at equal intervals along a line, are used to explore the microstructure of human cortical bone. Transects of 50 spectra taken at 2.5 μm intervals across an osteon show spatial differences in local mineral and protein composition as different physiological structures are traversed. Differences in mineral composition are seen near the rim of an osteon and further out in the lamellae. The blood vessel wall, primarily composed of collagen and elastin, is detected inside the Haversian canal. Factor analysis is used to explore the data set and reveals differences in mineral composition. Factor analysis also yields one bone matrix component, an osteoidal tissue component, and one blood vessel protein component. The 4 cm −1 spectral resolution and 2.5 μm spatial sampling facilitate the development of univariate metrics for bone development and health. Band integration is performed for important marker bands including phosphate v 1 at 960 cm −1 , monohydrogen phosphate v 1 at 1003 cm −1 , B-type carbonate v 1 at ∼ 1070 cm −1 , collagen CH 2 wag at ∼ 1450 cm −1 , and collagen amide I at ∼ 1650 cm −1 . Mineral-to-matrix ratio, phosphate-to-monohydrogen phosphate ratio, and carbonate-to-phosphate ratio are calculated from these measured areas.
Peptide-Mediated Inhibition of Neutrophil Transmigration by Blocking CD47 Interactions with Signal Regulatory Protein α (2004)

CD47, a cell surface transmembrane Ig superfamily member, is an extracellular ligand for signal regulatory protein (SIRPalpha). Interactions between CD47 and SIRPalpha regulate many important immune cell functions including neutrophil (PMN) transmigration. Here we report identification of a novel function-blocking peptide, CERVIGTGWVRC, that structurally mimics an epitope on CD47 and binds to SIRPalpha. The CERVIGTGWVRC sequence was identified by panning phage display libraries on the inhibitory CD47 mAb, C5D5. In vitro PMN migration assays demonstrated that peptide CERVIGTGWVRC specifically inhibited PMN migration across intestinal epithelial monolayers and matrix in a dose-dependent fashion. Further studies using recombinant proteins indicated that the peptide specifically blocks CD47 and SIRPalpha binding in a dose-dependent fashion. Protein binding assays using SIRPalpha domain-specific recombinant proteins demonstrated that this peptide directly bound to the distal-most Ig loop of SIRPalpha, the same loop where CD47 binds. In summary, these findings support the relevance of CD47-SIRPalpha interactions in regulation of PMN transmigration and provide structural data predicting the key residues involved on the surface of CD47. Such peptide reagents may be useful for studies on experimental models of inflammation and provide a template for the design of anti-inflammatory agents.
Optic neuritis in multiple sclerosis (2002)

AbstractPurpose: To review the clinical features, natural history, potential pathogenic mechanisms, differential diagnosis, and management of optic neuritis in multiple sclerosis. Methods: Relevant literature regarding optic neuritis in multiple sclerosis from 1970 to the present was reviewed. Results: Optic neuritis is an acute inflammatory optic neuropathy. It is the most common type of optic neuropathy causing acute visual loss in young adults (peak age at 30-40 years), especially among women. Patients usually present with an acute reduction of visual acuity, orbital pain exacerbated by eye movements, dyschromatopsia, and an afferent papillary defect, with or without swelling of the optic nerve head. Visual field testing most often reveals central defects, but others, such as centrocecal, can also occur. Magnetic resonance image (MRI) scanning of the brain should be undertaken in all cases of acute optic neuritis for diagnostic and prognostic purposes. The brain lesions of multiple sclerosis are commonly seen as T2 ovoid high-signal white matter lesions on MRI scans of the brain located in perivenular regions perpendicular to ventricles with variable enhancement. For atypical presentations of optic neuritis, additional laboratory tests, such as cerebrospinal fluid analysis, serologic tests, and visual evoked potentials, prove to be useful in the diagnosis and subsequent management of the patient. The recommended treatment for optic neuritis is intravenous steroids, as shown in the Optic Neuritis Treatment Trial (ONTT). Conclusion: Optic neuritis is often the initial presentation of multiple sclerosis. Recent advances in the understanding of the immune basis for multiple sclerosis has led to earlier and more effective treatment of this disease.
Mechanism Of Action Of Vitamin K: Synthesis Of Y-Carboxyglutamic Aci (1980)

Vitamin K (2-methyl-3-phytyl-1,4-naphthoquinone) is required for the synthesis of prothrombin, Factor VII, Factor IX, Factor X, and a number of newly discovered proteins. These plasma proteins participate in calcium-dependent phospholipid membrane interactions which are mediated through the presence of gamma-carboxyglutamyl residues in their amino-terminal region. Vitamin K is required for the postribosomal conversion of glutamyl residues in liver precursors of these proteins to gamma-carboxyglutamyl residues in the completed plasma proteins. In the absence of vitamin K, or in the presence of vitamin K antagonists, animals produce plasma forms which lack the carboxylated residue. These proteins are nonfunctional because of their lack of phospholipid interaction. The vitamin K-dependent carboxylase which carries out this reaction has been studied in rat liver microsomal preparations where it will carboxylate the endogenous precursor proteins. Low-molecular-weight glutamyl-containing peptide substrates, such as Phe-Leu-Glu-Glu-Leu, which are homologous to regions of the prothrombin precursor, will also serve as substrates for the detergent-solubilized enzyme. This enzyme has been shown to require the reduced form of the vitamin and O2 but no ATP or a biotin-containing protein for its activity. The same microsomal preparations will also convert vitamin K to its 2,3-epoxide, and it is possible that activity may be related to the role of the vitamin in driving the carboxylase reaction.