gebhart/patrepeval huggingface dataset:
Regulation of the human histamine H1 receptor stably expressed in Chinese hamster ovary cells (1996)

1. The human H1 receptor gene expressed in Chinese hamster ovary cells (CHOhumH1) encodes a classical histamine H1 receptor with a pharmacology similar to that of the H1 receptor found in guinea-pig cerebellum and the endogenously expressed human H1 receptor in 1321N1 astrocytoma cells as determined by [3H]-mepyramine binding studies. 2. In CHOhumH1 cells, histamine induced a concentration-dependent rise in inositol phosphates (EC50 2.23 +/- 0.97 microM) and a rapid increase of [Ca2+]i, followed by a sustained increase of [Ca2+]i upon addition of 100 microM histamine. 3. Short-term exposure of CHOhumH1 cells to histamine (100 microM) resulted in a decrease of subsequent histamine-induced Ca2+ responses. The histamine-induced desensitization appeared to be heterologous as the ATP-induced Ca2+ response was also found to be affected. 4. The process of heterologous histamine-induced desensitization of the Ca2+ response in CHOhumH1 cells can be ascribed to an alteration at the level of the intracellular Ca2+ pool, as the Ca2+ response of caffeine (10 mM), which releases Ca2+ from intracellular Ca2+ stores was also attenuated upon short-term histamine exposure. 5. In CHOhumH1 cells the PKC activator, PMA, was found to inhibit the histamine (100 microM)-induced Ca2+ response concentration-dependently (IC50 0.2 +/- 0.03 microM) as well as the ATP (100 microM)-induced Ca2+ response. However, this inhibition was only partial and less effective than histamine-pretreatment. Moreover, in CHOhumH1 cells PKC downregulation induced by long-term exposure to PMA (1 microM) did not affect the histamine-induced desensitization nor did pretreatment with the specific PKC inhibitor Ro-31-8220 (10 microM), indicating that in CHOhumH1 cells PKC is probably not involved in the heterologous desensitization. 6. Long-term treatment of CHOhumH1 cells with histamine or other H1 agonists resulted in a time- and concentration-dependent decrease in the number of H1 receptor binding sites (maximal reduction: 47 +/- 5%). 7. Long-term exposure of CHOhumH1 cells to ATP or PMA did not affect H1 receptor density. 8. Both histamine (100 microM)- and ATP (100 microM)-induced Ca2+ responses were affected upon long-term exposure of cells to histamine (100 microM), which might be explained by an alteration at a level distant from the receptor. 9. These results show that in CHOhumH1 cells the human histamine H1 receptor is susceptible to short-term and long-term receptor regulation in which PKC does not seem to play a role. The CHOhumH1 cells therefore provide an excellent model system for studying the mechanism(s) of PKC-independent H1 receptor regulation.
Spatially differing bacterial communities in water columns of the northern Baltic Sea (2010)

The Baltic Sea is a large, shallow, and strongly stratified brackish water basin. It suffers from eutrophication, toxic cyanobacterial blooms, and oxygen depletion, all of which pose a threat to local marine communities. In this study, the diversity and community structure of the northern Baltic Sea bacterial communities in the water column were, for the first time, thoroughly studied by 454 sequencing. The spring and autumn bacterial communities were one order of magnitude less diverse than those in recently studied oceanic habitats. Patchiness and strong stratification were clearly detectable; <1% of operational taxonomic units were shared among 11 samples. The community composition was more uniform horizontally (at a fixed depth) between different sites than vertically within one sampling site, implying that the community structure was affected by prevailing physical and hydrochemical conditions. Taxonomic affiliations revealed a total of 23 bacterial classes and 169 genera, while 5% of the sequences remained unclassified. The cyanobacteria accounted for <2% of the sequences, and potentially toxic cyanobacterial genera were essentially absent during the sampling seasons.
Quantitative Proteomic Analysis of Proteins Released by Neoplastic Prostate Epithelium (2004)

Prostate cancer is unusual among neoplasms in that it may be diagnosed at a curable stage through detection of a protein in serum, the serine protease prostate-specific antigen (PSA). PSA is secreted by both normal and neoplastic prostate epithelial cells in response to androgenic hormones and has found widespread use in cancer screening. Because PSA screening is controversial due to sensitivity and specificity issues, efforts continue to focus on the identification and characterization of additional markers that may be used for diagnostic and therapeutic purposes. In this study, we report the application of quantitative proteomic techniques that incorporate isotope coded affinity tag reagents and tandem mass spectrometry to comprehensively identify secreted and cell surface proteins from neoplastic prostate epithelium. LNCaP cells, a prostate tumor-derived cell line that secretes PSA in response to androgen exposure, were grown in a low protein-defined media under androgen-stimulated (A+) and -starved (A-) conditions. Proteomic analysis of the media identified in excess of 600 proteins, 524 of which could be quantified. Nine percent of the proteins had A+/A- ratios > 2.0, including PSA, and 2.5% had ratios < 0.5. A subset of these androgen-regulated proteins appeared to be expressed in abundance. Of these, selected mass spectrometry observations were confirmed by Western analysis. The findings suggest that androgen-mediated release of proteins may occur through the activation of proteolytic enzymes rather than exclusively through transcriptional or translational control mechanisms. On the basis of their known functional roles, several of the abundant androgen-regulated proteins may participate in the progression of neoplastic epithelial cell growth and should be considered as potential serum markers of neoplastic prostate diseases.
Dysfunctional cardiac mitochondrial bioenergetic, lipidomic, and signaling in a murine model of Barth syndrome (2013)

Barth syndrome is a complex metabolic disorder caused by mutations in the mitochondrial transacylase tafazzin. Recently, an inducible tafazzin shRNA knockdown mouse model was generated to deconvolute the complex bioenergetic phenotype of this disease. To investigate the underlying cause of hemodynamic dysfunction in Barth syndrome, we interrogated the cardiac structural and signaling lipidome of this mouse model as well as its myocardial bioenergetic phenotype. A decrease in the distribution of cardiolipin molecular species and robust increases in monolysocardiolipin and dilysocardiolipin were demonstrated. Additionally, the contents of choline and ethanolamine glycerophospholipid molecular species containing precursors for lipid signaling at the sn-2 position were altered. Lipidomic analyses revealed specific dysregulation of HETEs and prostanoids, as well as oxidized linoleic and docosahexaenoic metabolites. Bioenergetic interrogation uncovered differential substrate utilization as well as decreases in Complex III and V activities. Transgenic expression of cardiolipin synthase or iPLA2γ ablation in tafazzin-deficient mice did not rescue the observed phenotype. These results underscore the complex nature of alterations in cardiolipin metabolism mediated by tafazzin loss of function. Collectively, we identified specific lipidomic, bioenergetic, and signaling alterations in a murine model that parallel those of Barth syndrome thereby providing novel insights into the pathophysiology of this debilitating disease.
Identification of Insulin Receptor Substrate 1 (IRS-1) and IRS-2 as Signaling Intermediates in the α6β4 Integrin-Dependent Activation of Phosphoinositide 3-OH Kinase and Promotion of Invasion (2001)

Expression of the alpha6beta4 integrin increases the invasive potential of carcinoma cells by a mechanism that involves activation of phosphoinositide 3-OH kinase (PI3K). In the present study, we investigated the signaling pathway by which the alpha6beta4 integrin activates PI3K. Neither the alpha6 nor the beta4 cytoplasmic domain contains the consensus binding motif for PI3K, pYMXM, indicating that additional proteins are likely to be involved in the activation of this lipid kinase by the alpha6beta4 integrin. We identified insulin receptor substrate 1 (IRS-1) and IRS-2 as signaling intermediates in the activation of PI3K by the alpha6beta4 integrin. IRS-1 and IRS-2 are cytoplasmic adapter proteins that do not contain intrinsic kinase activity but rather function by recruiting proteins to surface receptors, where they organize signaling complexes. Ligation of the alpha6beta4 receptor promotes tyrosine phosphorylation of IRS-1 and IRS-2 and increases their association with PI3K, as determined by coimmunoprecipitation. Moreover, we identified a tyrosine residue in the cytoplasmic domain of the beta4 subunit, Y1494, that is required for alpha6beta4-dependent phosphorylation of IRS-2 and activation of PI3K in response to receptor ligation. Most importantly, Y1494 is essential for the ability of the alpha6beta4 integrin to promote carcinoma invasion. Taken together, these results imply a key role for the IRS proteins in the alpha6beta4-dependent promotion of carcinoma invasion.
Amantadine for Levodopa-Induced Dyskinesias (1999)

The beneficial effects of amantadine on motor response complications are maintained for at least 1 year after treatment initiation.
A unified spectral analysis of generalized time-hopping spread-spectrum signals in the presence of timing jitter (2002)

This paper characterizes the power spectral density (PSD) of various time-hopping spread-spectrum (TH-SS) signaling schemes in the presence of random timing jitter, which is characterized typically by a discrete-time stationary random process (independent of the TH sequences and data sequence) with known statistical properties. A flexible model for a general TH-SS signal is proposed and a unified spectral analysis of this generalized TH-SS signal is carried out using a systematic and tractable technique. The key idea is to express the basic baseband pulse in terms of its Fourier transform which allows flexibility in specifying different TH formats throughout the general derivation. The power spectrum of various TH-SS signaling schemes can then be obtained as a special case of the generalized PSD results. Although general PSD results are first obtained for arbitrary timing jitter statistics, specific results are then given for the cases of practical interest, namely, uniform and Gaussian distributed jitter. Applications of this unified spectral analysis includes: (1) clocked TH by a random sequence; (2) framed TH by a random sequence; and (3) framed TH by a pseudorandom periodic sequence. Detailed descriptions of these different TH techniques are given where the first two techniques employ a random sequence (stochastic model) and the third technique employs a pseudorandom sequence (deterministic model).
Targeting Vaccinia to Solid Tumors with Local Hyperthermia (2005)

We have previously demonstrated that mutant vaccinia viruses target tumors in vivo after systemic delivery, and they have potential as vectors for tumor-directed gene therapy. We hypothesized that hyperthermia may augment vaccinia delivery to tumors after systemic injection, as hyperthermia increases the permeability of the endothelial vasculature to nanoparticles. In our in vitro experiments, we have shown that hyperthermia does not alter tumor cells' susceptibility to the intrinsic cytopathogenicity of the vaccinia virus compared with normothermic controls. Hyperthermia also does not change the viral infectivity or the level of viral marker gene expression when compared with normothermia. In an in vitro model of endothelial cell monolayer permeability, we have demonstrated that hyperthermia increases the permeability of the monolayer to vaccinia virus and that this phenomenon is completely reversible. In vivo we have demonstrated that the tumors that were treated with systemic vaccinia under conditions of hyperthermia (41.5 degrees C for 30 min) had significantly higher levels of vaccinia marker gene activity (>100-fold) than those treated under normothermic conditions (p < 0.05) and that this effect was specific to tumor. We also demonstrated that mice with 1 cm subcutaneous tumors treated with a systemically delivered, conditionally replicating vaccinia under conditions of hyperthermia had complete tumor regression in 50% and significantly improved antitumor response, compared with normothermic viral-treated controls (mean tumor volume of 110 mm(3) vs 3169 mm(3), 13 days after treatment) and compared with hyperthermic, nonvirally treated control animals (p < 0.0001). Regional hyperthermia improves vaccinia targeting to tumors, and thereby enhances the antitumor response.
Ultrahigh Mobility in Polymer Field-Effect Transistors by Design (2011)

In this article, the design paradigm involving molecular weight, alkyl substituents, and donor-acceptor interaction for the poly[2,6-(4,4-bis-alkyl-4H-cyclopenta[2,1-b;3,4-b']-dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (cyclopentadithiophene-benzothiadiazole) donor-acceptor copolymer (CDT-BTZ) toward field-effect transistors (FETs) with ultrahigh mobilities is presented and discussed. It is shown that the molecular weight plays a key role in improving hole mobilities, reaching an exceptionally high value of up to 3.3 cm(2) V(-1) s(-1). Possible explanations for this observation is highlighted in conjunction with thin film morphology and crystallinity. Hereby, it is found that the former does not change, whereas, at the same time, crystallinity improved with ever growing molecular weight. Furthermore, other important structural design factors such as alkyl chain substituents and donor-acceptor interaction between the polymer backbones potentially govern intermolecular stacking distances crucial for charge transport and hence for device performance. In this aspect, for the first time we attempt to shed light onto donor-acceptor interactions between neighboring polymer chains with the help of solid state nuclear magnetic resonance (NMR). On the basis of our results, polymer design principles are inferred that might be of relevance for prospective semiconductors exhibiting hole mobilities even exceeding 3 cm(2) V(-1) s(-1).
Thermal Analysis Microscopy for the Study of Phase Changes in Fats (1985)

An investigation was carried out using the Mettler FPBOO Thermosystem to study polymorphic transitions of several monoacid triglycerides and hydrogenated Canola oil. The system includes a central processing unit connected with a thermal microscopy hot stage that allows the measurement of heat flow to the scrnple . Scanning electron microscopy was also used to examine the same samples after osmium tetroxide fixation . The results obtained relate phase transitions occurring during heating and cooling with the morphology of the various crystal structures.
A Dose-Response Study of Antibiotic Resistance in Pseudomonas aeruginosa Biofilms (2000)

Bacterial biofilms show enormous levels of antibiotic resistance, but little is known about the underlying molecular mechanisms. Multidrug resistance pumps (MDRs) are responsible for the extrusion of chemically unrelated antimicrobials from the bacterial cell. Contribution of the MDR-mediated efflux to antibiotic resistance of Pseudomonas aeruginosa biofilms was examined by using strains overexpressing and lacking the MexAB-OprM pump. Resistance of P. aeruginosa biofilms to ofloxacin was dependent on the expression of MexAB-OprM but only in the low concentration range. Unexpectedly, biofilm resistance to ciprofloxacin, another substrate of MexAB-OprM, did not depend on the presence of this pump. Dose-dependent killing indicated the presence of a small "superresistant" cell fraction. This fraction was primarily responsible for very high resistance of P. aeruginosa biofilms to quinolones. Bacterial cells recovered from a biofilm and tested under nongrowing conditions with tobramycin exhibited higher resistance levels than planktonic cells but lower levels than cells of an intact biofilm.
Lamellipodia and filopodia in metastasis and invasion (2008)

Advances in our understanding of the mechanisms of lamellipodia and filopodia assembly have led to a better concept of how cells move, including how the actin cytoskeleton might be important for the motility of metastatic cancer cells. The cytoskeleton is a potentially interesting target for prevention of invasion and metastasis. As key proteins are uncovered which regulate the assembly of actin-based structures, these need to be considered in light of whether they represent potential invasion and metastasis proteins.
A mitochondria-targeted S -nitrosothiol modulates respiration, nitrosates thiols, and protects against ischemia-reperfusion injury (2009)

Nitric oxide (NO(*)) competitively inhibits oxygen consumption by mitochondria at cytochrome c oxidase and S-nitrosates thiol proteins. We developed mitochondria-targeted S-nitrosothiols (MitoSNOs) that selectively modulate and protect mitochondrial function. The exemplar MitoSNO1, produced by covalently linking an S-nitrosothiol to the lipophilic triphenylphosphonium cation, was rapidly and extensively accumulated within mitochondria, driven by the membrane potential, where it generated NO(*) and S-nitrosated thiol proteins. MitoSNO1-induced NO(*) production reversibly inhibited respiration at cytochrome c oxidase and increased extracellular oxygen concentration under hypoxic conditions. MitoSNO1 also caused vasorelaxation due to its NO(*) generation. Infusion of MitoSNO1 during reperfusion was protective against heart ischemia-reperfusion injury, consistent with a functional modification of mitochondrial proteins, such as complex I, following S-nitrosation. These results support the idea that selectively targeting NO(*) donors to mitochondria is an effective strategy to reversibly modulate respiration and to protect mitochondria against ischemia-reperfusion injury.
Nucieotlde sequence analysis of alpha-arnylase and thiol protease genes that are hormonally regulated in barley aleurone cells (1987)

We have determined the nucleotide sequences of Amy32b, a type A alpha-amylase gene, and of the gene for aleurain, a thiol protease closely related to mammalian cathepsin H. Both are expressed in barley aleurone cells under control of the plant hormones gibberellic acid and abscisic acid, but only aleurain is expressed at high levels in other barley tissues. Sequence analysis indicates that the 5' end of the aleurain gene, comprising 3 exons and 2 introns, may have become associated with the remainder of the gene, encoding the protease domain of the protein, by some sort of recombination event. This 5' domain of the gene is very G + C-rich and is flanked by inverted repetitive sequences. We found two different groups of homologous sequence elements. The first group consists of four blocks of sequences conserved in the same spatial arrangement in both genes; these are arranged at similar intervals upstream from the Amy32b TATA box and from a TATA box present in intron 3 of aleurain, outside of the 5' domain and upstream from the protease domain. A part of two of these conserved sequences is similar to the core sequence of certain enhancer elements characterized from mammalian cells. The second group of homologous elements is present in the upstream region of both genes. We speculate that these conserved sets of sequences may have some role in either the tissue specificity of expression of the genes or in some part of the hormonal regulation imposed on them.
Autotracing ofEscherichia coliacetate CoA-transferase α-subunit structure using 3.4 Å MAD and 1.9 Å native data (2002)

The automation of protein structure determination is an essential component for high-throughput structural analysis in protein X-ray crystallography and is a key element in structural genomics. This highly challenging undertaking relies at present on the availability of high-quality native and derivatized protein crystals diffracting to high or moderate resolution, respectively. Obtaining such crystals often requires significant effort. The present study demonstrates that phases obtained at low resolution (>3.0 A) from crystals of SeMet-labeled protein can be successfully used for automated structure determination. The crystal structure of acetate CoA-transferase alpha-subunit was solved using 3.4 A multi-wavelength anomalous dispersion data collected from a crystal containing SeMet-substituted protein and 1.9 A data collected from a native protein crystal.
Effects of abnormal activation on the time course of the left ventricular pressure pulse in dilated cardiomyopathy (1992)

Values of QRS duration are unimodally distributed in patients with dilated cardiomyopathy, without evidence of a discrete group of patients with left bundle branch block. Prolonged QRS duration reduces peak +dP/dt, prolongs overall duration of the pressure pulse, the time to peak +dP/dt, and relaxation time. Duration of QRS must therefore be taken into account in assessing standard measurements of myocardial function in patients with dilated cardiomyopathy.
Probing Protein Structure and Function with an Expanded Genetic Code (1995)

Abstract A general biosynthetic method has been developed which makes it possible to site‐specifically incorporate unnatural amino acids with novel properties into proteins. In this approach the codon encoding the amino acid of interest is replaced with the “blank” nonsense codon UAG by oligonucleotide‐directed mutagenesis. A suppressor tRNA that recognizes this codon is generated by run‐off transcription and then chemically aminoacylated with the desired unnatural amino acid. Addition of the mutagenized gene and the aminoacylated suppressor tRNA to an in vitro extract capable of supporting protein biosynthesis generates a mutant protein containing the unnatural amino acid at the specified position. This methodology has recently been used to study the stability, specificity, and catalytic properties of a number of proteins. In these studies amino acids and analogues possessing altered hydrogen‐bonding, electronic, and steric properties and unique backbone conformations have all been site‐specifically incorporated into proteins. In addition, photoactivatable amino acids, isotopically labeled amino acids, and amino acids bearing biophysical probes have been inserted site‐specifically. This chemistry increases our ability to carry out detailed physical organic studies on this important class of macromolecules.
Structure of toxic shock syndrome toxin 1 (1993)

The three-dimensional structure of toxic shock syndrome toxin 1 (TSST-1) from Staphylococcus aureus has been determined and refined to an R value of 0.226 for data between 8- and 2.5-A resolution. Overall, the structure of TSST-1 is similar to that of another superantigen, staphylococcal enterotoxin B (SEB). The key differences between these molecules are in the amino termini and in the degree to which a long central helix is covered by surface loops. The region around the carboxyl end of this central helix is proposed to govern the superantigenic properties of TSST-1. An adjacent region along this helix is proposed to be critical in the ability of TSST-1 to induce toxic shock syndrome.
Population Biology of Antigen Presentation by MHC Class I Molecules (1996)

In principle, the function of major histocompatibility complex (MHC) molecules is simple: to bind a peptide and engage a T cell. In practice, placing this function within the context of the immune response begs questions of population biology; How does the immune response emerge from the interactions among populations of peptides, T cells and MHC molecules? Within a population of vertebrates, how does MHC polymorphism stamp individuality on the response? Does polymorphism confer differential advantages in responding to parasites? How are the pressures on the MHC reflected in turnover of alleles? The role of mutation, recombination, selection, and drift in the generation and maintenance of MHC class 1 polymorphism are considered.