gebhart/patrepeval huggingface dataset:
Host Response to Infection: the Role of CpG DNA in Induction of Cyclooxygenase 2 and Nitric Oxide Synthase 2 in Murine Macrophages (2001)

Depending on sequence, bacterial and synthetic DNAs can activate the host immune system and influence the host response to infection. The purpose of this study was to determine the abilities of various phosphorothioate oligonucleotides with cytosine-guanosine-containing motifs (CpG DNA) to activate macrophages to produce nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and to induce expression of NO synthase 2 (NOS2) and cyclooxygenase 2 (COX2). As little as 0.3 microg of CpG DNA/ml increased NO and PGE(2) production in a dose- and time-dependent fashion in cells of the mouse macrophage cell line J774. NO and PGE(2) production was noted by 4 to 8 h after initiation of cultures with the CpG DNA, with the kinetics of NO production induced by CpG DNA being comparable to that induced by a combination of lipopolysaccharide and gamma interferon. CpG DNA-treated J774 cells showed enhanced expression of NOS2 and COX2 proteins as determined by immunoblotting, with the relative potencies of the CpG DNAs generally corresponding to those noted for the induction of NO and PGE(2) production as well as to those noted for the induction of interleukin-6 (IL-6), IL-12, and tumor necrosis factor. Extracts from CpG DNA-treated cells converted L-arginine to L-citrulline, but the NOS inhibitor N(G)-monomethyl-L-arginine (NMMA) inhibited this reaction. The COX2-specific inhibitor NS398 inhibited CpG DNA-induced PGE(2) production and inhibited NO production to various degrees. The NOS inhibitors NMMA, 1400W, and N-iminoethyl-L-lysine effectively blocked NO production and increased the production of PGE(2) in a dose-dependent fashion. Thus, analogues of microbial DNA (i.e., CpG DNA) activate mouse macrophage lineage cells for the expression of NOS2 and COX2, with the production of NO and that of PGE(2) occurring in an interdependent manner.
Apolipoprotein A-I-stimulated Apolipoprotein E Secretion from Human Macrophages Is Independent of Cholesterol Efflux (2004)

Apolipoprotein A-I (apoA-I)-mediated cholesterol efflux involves the binding of apoA-I to the plasma membrane via its C terminus and requires cellular ATP-binding cassette transporter (ABCA1) activity. ApoA-I also stimulates secretion of apolipoprotein E ( apoE) from macrophage foam cells, although the mechanism of this process is not understood. In this study, we demonstrate that apoA-I stimulates secretion of apoE independently of both ABCA1-mediated cholesterol efflux and of lipid binding by its C terminus. Pulse-chase experiments using S-35-labeled cellular apoE demonstrate that macrophage apoE exists in both relatively mobile ( Em) and stable (E-s) pools, that apoA-I diverts apoE from degradation to secretion, and that only a small proportion of apoA-I-mobilized apoE is derived from the cell surface. The structural requirements for induction of apoE secretion and cholesterol efflux are clearly dissociated, as C-terminal deletions in recombinant apoA-I reduce cholesterol efflux but increase apoE secretion, and deletion of central helices 5 and 6 decreases apoE secretion without perturbing cholesterol efflux. Moreover, a range of 11- and 22-mer alpha-helical peptides representing amphipathic alpha-helical segments of apoA-I stimulate apoE secretion whereas only the C-terminal alpha-helix ( domains 220 - 241) stimulates cholesterol efflux. Other alpha-helix-containing apolipoproteins (apoA-II, apoA-IV, apoE2, apoE3, apoE4) also stimulate apoE secretion, implying a positive feedback autocrine loop for apoE secretion, although apoE4 is less effective. Finally, apoA-I stimulates apoE secretion normally from macrophages of two unrelated subjects with genetically confirmed Tangier Disease ( mutations C733R and c. 5220 - 5222delTCT; and mutations A1046D and c. 4629 - 4630insA), despite severely inhibited cholesterol efflux. We conclude that apoA-I stimulates secretion of apoE independently of cholesterol efflux, and that this represents a novel, ABCA-1-independent, positive feedback pathway for stimulation of potentially anti-atherogenic apoE secretion by alpha-helix-containing molecules including apoA-I and apoE.
Prospects of photoacoustic tomography (2008)

Commercially available high-resolution three-dimensional optical imaging modalities-including confocal microscopy, two-photon microscopy, and optical coherence tomography-have fundamentally impacted biomedicine. Unfortunately, such tools cannot penetrate biological tissue deeper than the optical transport mean free path (approximately 1 mm in the skin). Photoacoustic tomography, which combines strong optical contrast and high ultrasonic resolution in a single modality, has broken through this fundamental depth limitation and achieved superdepth high-resolution optical imaging. In parallel, radio frequency-or microwave-induced thermoacoustic tomography is being actively developed to combine radio frequency or microwave contrast with ultrasonic resolution. In this Vision 20/20 article, the prospects of photoacoustic tomography are envisaged in the following aspects: (1) photoacoustic microscopy of optical absorption emerging as a mainstream technology, (2) melanoma detection using photoacoustic microscopy, (3) photoacoustic endoscopy, (4) simultaneous functional and molecular photoacoustic tomography, (5) photoacoustic tomography of gene expression, (6) Doppler photoacoustic tomography for flow measurement, (7) photoacoustic tomography of metabolic rate of oxygen, (8) photoacoustic mapping of sentinel lymph nodes, (9) multiscale photoacoustic imaging in vivo with common signal origins, (10) simultaneous photoacoustic and thermoacoustic tomography of the breast, (11) photoacoustic and thermoacoustic tomography of the brain, and (12) low-background thermoacoustic molecular imaging.
Opioid peptides derived from wheat gluten: Their isolation and characterization (1992)

Four opioid peptides were isolated from the enzymatic digest of wheat gluten. Their structures were Gly-Tyr-Tyr-Pro-Thr, Gly-Tyr-Tyr-Pro,Tyr-Gly-Gly-Trp-Leu and Tyr-Gly-Gly-Trp, which were named gluten exorphins A5, A4, B5 and B4, respectively. The gluten exorphin A5 sequence was found at 15 sites in the primary structure of the high molecular weight glutenin and was highly specific for delta-receptors. The structure-activity relationships of gluten exorphins A were unique in that the presence of Gly at their N-termini increased their activities. Gluten exorphin B5, which corresponds to [Trp4,Leu5]enkephalin, showed the most potent activity among these peptides. Its IC50 values were 0.05 microM and 0.017 microM, respectively, on the GPI and the MVD assays.
Brain mechanisms for offense, defense, and submission (1979)

Abstract A preliminary attempt is made to analyze the intraspecific aggressive behavior of mammals in terms of specific neural circuitry. The results of stimulation, lesion, and recording studies of aggressive behavior in cats and rats are reviewed and analyzed in terms of three hypothetical motivational systems: offense, defense, and submission. A critical distinction, derived from ethological theory, is made between motivating stimuli that simultaneously activate functional groupings of motor patterning mechanisms, and releasing and directing stimuli that are necessary for the activation of discrete motor patterning mechanisms. It is suggested that motivating stimuli activate pathways that converge upon sets of homogeneous neurons, called motivational mechanisms, whose activity determines the motivational state of the animal. A defense motivational mechanism is hypothesized to be located in the midbrain central gray. In addition to tactile, auditory, and visual inputs from the paleospinothalamic tract, lateral lemniscus, and (perhaps) from the pretectum, it may receive inputs from a major forebrain pathway whose functional significance is not yet understood. A submission motivational mechanism is also thought to be located in the central gray. In addition to inputs for defense, it is thought to receive a necessary input from a “consociate (social familiarity cue) modulator” located in the ventromedial hypothalamus, which can switch behavior from defense to submission. The location of the hypothetical offense motivational mechanism is not known, although the pathways by which it is activated are traced in some detail. Brain mechanisms of aggression in primitive mammals and in primates are apparently similar to those in rats and cats.
Sperm Plasma Membrane Remodeling during Spermiogenetic Maturation in Men: Relationship among Plasma Membrane β 1,4-Galactosyltransferase, Cytoplasmic Creatine Phosphokinase, and Creatine Phosphokinase Isoform Ratios1 (1997)

Sperm creatine phosphokinase (CK) concentrations and the synthesis of the CK-M isoform reflect normal spermiogenesis and predict maturity and fertilizing potential of ejaculated human spermatozoa. Immature spermatozoa, characterized by cytoplasmic retention and low CK-M to CK-B isoform ratios, are deficient in zona binding and fail to cause pregnancies. Because these sperm lack zona-binding ability, we examined in this study whether beta 1,4-galactosyltransferase (GalTase), a key element of sperm-zona interactions in mice, is diminished in immature human sperm. Unexpectedly, GalTase was overexpressed in immature sperm relative to mature sperm: the levels of cytoplasmic CK and plasma membrane GalTase were positively correlated (r = 0.78, p < 0.001, n = 88). Sperm populations with various levels of cellular maturity, prepared by Percoll gradients, had different CK and GalTase concentrations, but within each subpopulation the relationship between CK and GalTase was maintained (p < 0.01-0.001). GalTase activities in intact and vortex-disrupted sperm fractions were similar, showing that GalTase is present on the surface membrane of human sperm--similar to the situation in all other species assayed. The changes previously reported by our laboratory in zona-binding ability and lipid peroxidation rates (which occur simultaneously with cytoplasmic extrusion), decline in CK activity, and increased expression of the CK-M isoform are suggestive of a remodeling of the sperm surface concomitant with cytoplasmic maturation. The changes reported here in GalTase expression on the surface of maturing spermatozoa prove this hypothesis.
Trapping and Stabilization of Integral Membrane Proteins by Hydrophobically Grafted Glucose-Based Telomers (2009)

Amphipols (APols) are short amphipathic polymers designed to adsorb onto the transmembrane surface of membrane proteins, keeping them water-soluble in the absence of detergent. Current APols carry charged groups, which is a limitation for certain types of applications. This has prompted the development of totally nonionic amphiphols (NAPols). In a previous work, glucose-based NAPols synthesized by free-radical cotelomerization of hydrophilic and amphiphilic monomers proved to be able to keep membrane proteins soluble (Sharma et al. Langmuir 2008, 24, 13581-13590). This provided a proof of principle, but the cumbersome synthesis prevented large-scale production and any detailed biochemical studies. In the present work, we describe a new synthesis route for NAPols based on grafting alkyl chains onto a glucosylated homotelomer. The NAPols thus prepared are highly water soluble. In aqueous solutions, they assemble into small, homogeneous particles similar to those formed by ionic APols. Two model membrane proteins, bacteriorhodopsin and the transmembrane domain of OmpA, form with NAPols small, well-defined water-soluble complexes whose size is comparable to that observed with ionic APols. Complexation by NAPols strongly stabilizes bacteriorhodopsin against denaturation. Glucosylated NAPols thus appear as a promising alternative to ionic APols for such applications as ion-exchange chromatography, isoelectrofocusing, and, possibly, structural approaches such as NMR and crystallography.
Crystal structure of prethrombin-1 (2010)

Prothrombin is the zymogen precursor of the clotting enzyme thrombin, which is generated by two sequential cleavages at R271 and R320 by the prothrombinase complex. The structure of prothrombin is currently unknown. Prethrombin-1 differs from prothrombin for the absence of 155 residues in the N-terminal domain and is composed of a single polypeptide chain containing fragment 2 (residues 156-271), A chain (residues 272-320), and B chain (residues 321-579). The X-ray crystal structure of prethrombin-1 solved at 2.2-Å resolution shows an overall conformation significantly different (rmsd = 3.6 Å) from that of its active form meizothrombin desF1 carrying a cleavage at R320. Fragment 2 is rotated around the y axis by 29° and makes only few contacts with the B chain. In the B chain, the oxyanion hole is disrupted due to absence of the I16-D194 ion pair and the Na(+) binding site and adjacent primary specificity pocket are highly perturbed. A remarkable feature of the structure is that the autolysis loop assumes a helical conformation enabling W148 and W215, located 17 Å apart in meizothrombin desF1, to come within 3.3 Å of each other and completely occlude access to the active site. These findings suggest that the zymogen form of thrombin possesses conformational plasticity comparable to that of the mature enzyme and have significant implications for the mechanism of prothrombin activation and the zymogen → protease conversion in trypsin-like proteases.
Quantum error correction of continuous-variable states against Gaussian noise (2011)

We describe a continuous-variable error correction protocol that can correct the Gaussian noise induced by linear loss on Gaussian states. The protocol can be implemented using linear optics and photon counting. We explore the theoretical bounds of the protocol as well as the expected performance given current knowledge and technology.
De novo sequencing of plant genomes using second-generation technologies (2009)

The ability to sequence the DNA of an organism has become one of the most important tools in modern biological research. Until recently, the sequencing of even small model genomes required substantial funds and international collaboration. The development of 'second-generation' sequencing technology has increased the throughput and reduced the cost of sequence generation by several orders of magnitude. These new methods produce vast numbers of relatively short reads, usually at the expense of read accuracy. Since the first commercial second-generation sequencing system was produced by 454 Technologies and commercialised by Roche, several other companies including Illumina, Applied Biosystems, Helicos Biosciences and Pacific Biosciences have joined the competition. Because of the relatively high error rate and lack of assembly tools, short-read sequence technology has mainly been applied to the re-sequencing of genomes. However, some recent applications have focused on the de novo assembly of these data. De novo assembly remains the greatest challenge for DNA sequencing and there are specific problems for second generation sequencing which produces short reads with a high error rate. However, a number of different approaches for short-read assembly have been proposed and some have been implemented in working software. In this review, we compare the current approaches for second-generation genome sequencing, explore the future direction of this technology and the implications for plant genome research.
SNAI1 is critical for the aggressiveness of prostate cancer cells with low E-cadherin (2014)

Together, these results suggest that E-cadherin loss promotes SNAI1 expression that controls the aggressiveness of PCA cells.
Effect of Hemorrhagic Hypotension and Hypoventilation on Lower Esophageal Sphincter Pressure (1980)

Dysfunction of the lower esophageal sphincter has been demonstrated in the cat shock model. Analogies have been drawn to reflux and aspiration in the critically ill patient. In a cat shock model, lower esophageal sphincter pressure is reduced and response to bethanechol is impaired. Upon resuscitation to basal state with heparinized shed blood, the lower esophageal basal pressure returns to normal values, and response to bethanechol is restored. This model may explain reflux and aspiration in the critically ill patient.
Appetite, hunger, and satiety in the elderly (1993)

Food intake declines with age and the elderly frequently report a decrease in appetite. Social and physical factors as well as decreased energy expenditure may be part of the explanation for the decreased food intake; however, it is possible that changes in hunger mechanisms are also involved, but more studies similar to those conducted on thirst are needed. The consumption of a varied diet depends in part on sensory-specific satiety, that is, the decrease in the pleasantness of a food as it is consumed. We have shown that sensory-specific satiety changes with age such that it was absent in individuals over the age of 65 and this could be part of the explanation of why the elderly consume more monotonous diets. Additional basic studies on how aging affects the controls of food intake will suggest ways to improve the nutritional status of the elderly.
Acylated and Unacylated Ghrelin Promote Proliferation and Inhibit Apoptosis of Pancreatic β-Cells and Human Islets: Involvement of 3′,5′-Cyclic Adenosine Monophosphate/Protein Kinase A, Extracellular Signal-Regulated Kinase 1/2, and Phosphatidyl Inositol 3-Kinase/Akt Signaling (2006)

Among its pleiotropic actions, ghrelin modulates insulin secretion and glucose metabolism. Herein we investigated the role of ghrelin in pancreatic beta-cell proliferation and apoptosis induced by serum starvation or interferon (IFN)-gamma/TNF-alpha, whose synergism is a major cause for beta-cell destruction in type I diabetes. HIT-T15 beta-cells expressed ghrelin but not ghrelin receptor (GRLN-R), which binds acylated ghrelin (AG) only. However, both unacylated ghrelin (UAG) and AG recognized common high-affinity binding sites on these cells. Either AG or UAG stimulated cell proliferation through Galpha(s) protein and prevented serum starvation- and IFN-gamma/TNF-alpha-induced apoptosis. Antighrelin antibody enhanced apoptosis in either the presence or absence of serum but not cytokines. AG and UAG even up-regulated intracellular cAMP. Blockade of adenylyl cyclase/cAMP/protein kinase A signaling prevented the ghrelin cytoprotective effect. AG and UAG also activated phosphatidyl inositol 3-kinase (PI3K)/Akt and ERK1/2, whereas PI3K and MAPK inhibitors counteracted the ghrelin antiapoptotic effect. Furthermore, AG and UAG stimulated insulin secretion from HIT-T15 cells. In INS-1E beta-cells, which express GRLN-R, AG and UAG caused proliferation and protection against apoptosis through identical signaling pathways. Noteworthy, both peptides inhibited cytokine-induced NO increase in either HIT-T15 or INS-1E cells. Finally, they induced cell survival and protection against apoptosis in human islets of Langerhans. These expressed GRLN-R but showed also UAG and AG binding sites. Our data demonstrate that AG and UAG promote survival of both beta-cells and human islets. These effects are independent of GRLN-R, are likely mediated by AG/UAG binding sites, and involve cAMP/PKA, ERK1/2, and PI3K/Akt.
Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience (2018)

These data support the safety and efficacy of nal-IRI + 5-FU/LV, reinforcing results of NAPOLI-1. Patients without disease progression on prior irinotecan fared significantly better than patients with progression, when treated with nal-IRI + 5-FU/LV. Sequential therapy with nab-P + Gem followed by nal-IRI + 5-FU/LV demonstrates encouraging median OS. These findings provide guidance for patients most likely to benefit from nal-IRI + 5-FU/LV.
Stable Lanthanide Luminescence Agents Highly Emissive in Aqueous Solution:  Multidentate 2-Hydroxyisophthalamide Complexes of Sm3+, Eu3+, Tb3+, Dy3+ (2003)

Efficient lanthanide (Ln) luminescent probes require good ligand-to-metal energy transfer and high aqueous stability. A family of ligands based on 2-hydroxyisophthalamide chelating units is reported. These form highly stable, eight-coordinate Ln complexes. Several of these (Ln = Sm, Eu, Tb, Dy) emit in the visible region with good ligand-to-lanthanide energy transfer. The absolute quantum yields of the two Tb complexes studies (Phi = 0.59, 0.61) and high absorbance make these the brightest luminescent probes for time-resolved detection; the emission spectrum of one complex can be seen down to 10-15 M. The low overlap of the four different Ln complexes enables their simultaneous detection and discrimination.
The homodimer of prostate-specific membrane antigen is a functional target for cancer therapy (2003)

Prostate-specific membrane antigen (PSMA) is a type 2 integral membrane glycoprotein that serves as an attractive target for cancer immunotherapy by virtue of its abundant and restricted expression on the surface of prostate carcinomas and the neovasculature of most other solid tumors. However, relatively little is known about the molecular structure of this target. Here, we report that PSMA is expressed on tumor cells as a noncovalent homodimer. A truncated PSMA protein, lacking transmembrane and cytoplasmic domains, also formed homodimers, indicating that the extracellular domain is sufficient for dimerization. PSMA dimers but not monomers displayed a native conformation and possessed high-level carboxypeptidase activity. A unique dimer-specific epitope was identified by using one of a panel of novel mAbs. When used to immunize animals, dimer but not monomer elicited antibodies that efficiently recognized PSMA-expressing tumor cells. These findings on PSMA structure and biology may have important implications for active and passive immunotherapy of prostate and other cancers.
Continuous Glucose Detection Using Boronic Acid-Substituted Viologens in Fluorescent Hydrogels:  Linker Effects and Extension to Fiber Optics (2006)

A fluorescent anionic dye and a viologen appended with boronic acids, which serve as glucose receptors, have been synthesized and immobilized into a poly(2-hydroxyethyl methacrylate) hydrogel for use as a continuous glucose monitor. The fluorescence of the dye is modulated by the quenching efficiency of the viologen-based receptor, which in turn is dependent on the glucose concentration. Two monomeric versions of the quencher/receptor unit were prepared and their performance within the hydrogel evaluated. By tethering the quencher/receptor to the hydrogel matrix using a single-point attachment, slightly improved glucose sensing was observed. The hydrogels were tested for their ability to continuously and reversibly detect glucose over the course of several hours. The tests were carried out using a cuvette-based system, as well as a fiber-optic-based configuration. Under physiological conditions (0.1 M phosphate buffer, pH 7.4, 37 degrees C), the fluorescent hydrogels display an excellent dynamic response to glucose concentrations within the biologically significant range (2.5-20 mM).
Cholera Strengthened by Trip Through Gut (2002)

Poor sanitation promotes the spread of cholera, but that's not the only way humans foster the deadly diarrheal disease. Microbiologists have discovered that the human gut seems to prime the bacteria responsible. Before Vibrio cholerae exit the body in watery stools, something about the intestinal environment causes them to rev up the activity of certain genes. These genes, in turn, seem to prepare them for ever more effective colonization of their next victims, possibly fueling epidemics, says Andrew Camilli, a microbiologist at Tufts University School of Medicine in Boston.