gebhart/patrepeval huggingface dataset:
Altered glycan-dependent signaling induces insulin resistance and hyperleptinemia (2002)

Insulin resistance and beta cell toxicity are key features of type 2 diabetes. One leading hypothesis suggests that these abnormalities result from excessive flux of nutrients through the UDP-hexosamine biosynthetic pathway leading to "glucose toxicity." How the products of the hexosamine pathway mediate these effects is not known. Here, we show that transgenic overexpression of an enzyme using UDP-GlcNAc to modify proteins with O-GlcNAc produces the type 2 diabetic phenotype. Even modest overexpression of an isoform of O-GlcNAc transferase, in muscle and fat, leads to insulin resistance and hyperleptinemia. These data support the proposal that O-linked GlcNAc transferase participates in a hexosamine-dependent signaling pathway that is linked to insulin resistance and leptin production.
Simian immunodeficiency virus displays complex patterns of RNA splicing (1990)

The human and simian immunodeficiency viruses encode at least six gene products that apparently serve regulatory functions. To evaluate the regulation of simian immunodeficiency virus gene expression at the level of RNA splicing, we used the polymerase chain reaction to amplify and clone cDNAs corresponding to a large array of mRNAs from infected cells. We identified mRNAs that used splice acceptor sites upstream of the initiator codons for tat, rev, vpr, nef, vif, and vpx, suggesting that these proteins may be expressed from different mRNAs. We also provide hybridization data suggesting that the same splice acceptor site may be used for both rev and env mRNAs. Furthermore, we isolated both tat and rev cDNAs that utilized three alternative splice acceptor sites at the start of coding exon 2, indicating that different versions of these proteins may be encoded. Finally, approximately 10 to 20% of simian immunodeficiency virus mRNAs spliced an intron from their untranslated 5' ends, and sequences contained within this intron constituted a portion of the tat-responsive TAR element. Thus, alternative pre-mRNA splicing adds a level of complexity to simian immunodeficiency virus expression, which may affect several levels of gene regulation.
The Radiation-induced Inactivation of External Yeast Invertase in Dilute Aqueous Solution (1989)

The inactivation of external yeast invertase by irradiation in dilute aqueous solution has been investigated. The contributions of the individual radical species from water radiolysis to inactivation and amino acid degradation were estimated from the results of experiments in which solutions were saturated with nitrogen, nitrous oxide or oxygen, and on addition of hydroxyl radical scavengers. Under conditions where inactivation by hydroxyl radicals predominates, the rate of inactivation increased with increasing dose, indicating that in the initial stages of the radiolysis the mannose-rich oligosaccharide chains of the glycoprotein protect the polypeptide chain from radical attack. Amino acid analysis of the irradiated external invertase showed that there was significant destruction of tyrosine, phenylalanine, methionine and histidine residues. Destruction of methionine and histidine residues may be responsible for the free radical-induced inactivation of this enzyme.
A reconfigurable optoelectronic wavelength converter based on an integrated electroabsorption modulated laser array (2002)

Optical wavelength conversion or wavelength adaptation is a desired functionality for evolving WDM network architectures. The ability to perform routing and switching as a function of wavelength in a network can be achieved through wavelength conversion. The one feature necessary for all wavelength converters is the ability to provide a new wavelength which complies with the specified wavelengths in the system. We describe an optoelectronic wavelength converter in which the new wavelength is provided by an integrated electroabsorption modulated laser (EML) array suitable for low-chirp long haul transmission. The converter consists of a photodiode which converts the input optical signal to an electrical signal. This signal is amplified to drive an EA modulator which is integrated with a DFB laser array, passive optical power combiner and optical amplifier. Each laser in the array has a different grating and thus lases at a different wavelength in the 1550 to 1560 nm region. The transmitter can be configured to provide either selected fixed wavelength output or to switch between output wavelengths as determined by network control. We demonstrate the operation of the wavelength converter at 2.5 Gbits/s. The output wavelength is switched between compliant wavelengths spaced by 200 GHz through software control and bit-error-rate (BER) performance is measured.
Toll‐like receptors in rheumatic diseases: Are we paying a high price for our defense against bugs? (2011)

In the last decade Toll-like receptor (TLR) research has led to new insights in the pathogenesis of many rheumatic diseases. In autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis TLR signaling is likely to be involved in tolerance breakthrough and chronic inflammation via combined Fc gamma receptors and TLR recognition of immune complexes. Furthermore, inflammatory diseases like psoriatic arthritis and gout also show more and more evidence for TLR involvement. In this review we will discuss the involvement of TLR signaling in several rheumatic diseases and stress their similarities and differences based on recent findings.
Cellular basis of chronic ventricular remodeling after myocardial infarction in rats. (1991)

To determine whether the hypertrophic response of the surviving myocardium after infarction leads to normalization of ventricular hemodynamics and wall stress, the left coronary artery was ligated in rats. One month later, the rats were killed. In infarcts affecting an average 38% of the free wall of the left ventricle (small infarcts), reactive hypertrophy in the spared myocardium bordering and remote from the scar was documented by increases in myocyte cell volume per nucleus of 43% and 25%, respectively. These cellular enlargements resulted in a complete reconstitution of functioning tissue. However, left ventricular end-diastolic pressure was increased, left ventricular dP/dt was decreased, and diastolic wall stress was increased 2.4-fold. After infarctions resulting in a 60% loss of mass (large infarcts), myocyte hypertrophy was 81% and 32% in the regions adjacent to and distant from the scar, respectively. A 10% deficit was present in the recovery of viable myocardium. Functionally, ventricular performance was markedly depressed, and diastolic wall stress was increased ninefold. The alterations in loading of the spared myocardium were due to an increase in chamber volume and a decrease in the myocardial mass/chamber volume ratio that affected both infarct groups. Chamber dilation was the consequence of the combination of gross anatomic and cellular changes consisting, in the presence of small infarcts, of a 6% and a 19% increase in transverse midchamber diameter and in average myocyte length per nucleus, respectively. In the presence of large infarcts, transverse and longitudinal chamber diameters expanded by 27% and 11%, respectively, myocyte length per nucleus expanded by 26%, and the mural number of myocytes decreased by 10%. In conclusion, decompensated eccentric ventricular hypertrophy develops chronically after infarction, and growth processes in myocytes are inadequate for normalization of wall stress when myocyte loss involves nearly 40% or more of the cells of the left ventricular free wall. The persistance of elevated myocardial and cellular loads may sustain the progression of the disease state toward end-stage congestive heart failure.
Molecular basis of anti‐inflammatory action of platelet‐rich plasma on human chondrocytes: Mechanisms of NF‐κB inhibition via HGF (2010)

Loss of articular cartilage through injury or disease presents major clinical challenges also because cartilage has very poor regenerative capacity, giving rise to the development of biological approaches. As autologous blood product, platelet-rich plasma (PRP) provides a promising alternative to surgery by promoting safe and natural healing. Here we tested the possibility that PRP might be effective as an anti-inflammatory agent, providing an attractive basis for regeneration of articular cartilage, and two principal observations were done. First, activated PRP in chondrocytes reduced the transactivating activity of NF-κB, critical regulator of the inflammatory process, and decreased the expression of COX-2 and CXCR4 target genes. By analyzing a panel of cytokines with different biological significance, in activated PRP we observed increases in hepatocyte growth factor (HGF), interleukin-4 and tumor necrosis factor-α (TNF-α). HGF and TNF-α, by disrupting NF-κB-transactivating activity, were important for the anti-inflammatory function of activated PRP. The key molecular mechanisms involved in PRP-inhibitory effects on NF-κB activity were for HGF the enhanced cellular IkBα expression, that contributed to NF-κB-p65 subunit retention in the cytosol and nucleo-cytoplasmic shuttling, and for TNF-α the p50/50 DNA-binding causing inhibition of target-gene expression. Second, activated PRP in U937-monocytic cells reduced chemotaxis by inhibiting chemokine transactivation and CXCR4-receptor expression, thus possibly controlling local inflammation in cartilage. In conclusion, activated PRP is a promising biological therapeutic agent, as a scaffold in micro-invasive articular cartilage regeneration, not only for its content of proliferative/differentiative growth factors, but also for the presence of anti-inflammatory agents including HGF.
Epigenetic pathway targets for the treatment of disease: accelerating progress in the development of pharmacological tools:IUPHARReview 11 (2014)

The properties of a cell are determined both genetically by the DNA sequence of its genes and epigenetically through processes that regulate the pattern, timing and magnitude of expression of its genes. While the genetic basis of disease has been a topic of intense study for decades, recent years have seen a dramatic increase in the understanding of epigenetic regulatory mechanisms and a growing appreciation that epigenetic misregulation makes a significant contribution to human disease. Several large protein families have been identified that act in different ways to control the expression of genes through epigenetic mechanisms. Many of these protein families are finally proving tractable for the development of small molecules that modulate their function and represent new target classes for drug discovery. Here, we provide an overview of some of the key epigenetic regulatory proteins and discuss progress towards the development of pharmacological tools for use in research and therapy.
Ultrafast Carrier Dynamics in Single-Wall Carbon Nanotubes (2003)

Time-resolved carrier dynamics in single-wall carbon nanotubes is investigated by means of two-color pump-probe experiments. The recombination dynamics is monitored by probing the transient photobleaching observed on the interband transitions of the semiconducting tubes. This dynamics takes place on a 1 ps time scale which is 1 order of magnitude slower than in graphite. Transient photoinduced absorption is observed for nonresonant probing and is interpreted as a global redshift of the pi-plasmon resonance. We show that the opening of the band gap in semiconducting carbon nanotubes determines the nonlinear response dynamics over the whole visible and near-infrared spectrum.
Reductions in acidic amino acids andN-acetylaspartylglutamate in amyotrophic lateral sclerosis CNS (1991)

Acidic excitatory amino acids have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). We now report that, in addition to selective regional reductions in endogenous aspartate and glutamate, N-acetylaspartate (NAA), and N-acetylaspartylglutamate (NAAG) are also decreased in the CNS, whereas the activity of N-acetylated-alpha-linked-amino dipeptidase (NAALADase) is increased. In cervical cord, the concentrations of aspartate and glutamate were decreased significantly in the ventral horn; NAA was decreased in the ventral horn, dorsal horn and ventral column, whereas NAAG was decreased in all regions of the cord examined, except the posterior column. NAALADase activity was increased in the ventral column. In motor cortex of ALS patients, aspartate and glutamate were decreased and NAALADase activity was increased in both gray and white matter; whereas NAAG was decreased in gray matter alone. None of these parameters was affected in the cerebral cortex of the Huntington's patients. Of the markers examined, the alterations in the levels of NAAG most closely parallel the cellular neuropathology in ALS.
A guided tour into subcellular colocalization analysis in light microscopy (2006)

It is generally accepted that the functional compartmentalization of eukaryotic cells is reflected by the differential occurrence of proteins in their compartments. The location and physiological function of a protein are closely related; local information of a protein is thus crucial to understanding its role in biological processes. The visualization of proteins residing on intracellular structures by fluorescence microscopy has become a routine approach in cell biology and is increasingly used to assess their colocalization with well-characterized markers. However, image-analysis methods for colocalization studies are a field of contention and enigma. We have therefore undertaken to review the most currently used colocalization analysis methods, introducing the basic optical concepts important for image acquisition and subsequent analysis. We provide a summary of practical tips for image acquisition and treatment that should precede proper colocalization analysis. Furthermore, we discuss the application and feasibility of colocalization tools for various biological colocalization situations and discuss their respective strengths and weaknesses. We have created a novel toolbox for subcellular colocalization analysis under ImageJ, named JACoP, that integrates current global statistic methods and a novel object-based approach.
Iron Overload and Diabetes Risk: A Shift From Glucose to Fatty Acid Oxidation and Increased Hepatic Glucose Production in a Mouse Model of Hereditary Hemochromatosis (2010)

Increased hepatic glucose production and metabolic inflexibility, both of which are characteristics of type 2 diabetes, may contribute to the risk of diabetes with excessive tissue iron.
Concise Review: Deconstructing the Lung to Reveal Its Regenerative Potential (2012)

Despite burgeoning interest in the potential of cellular therapies in lung regenerative medicine, progress in delivering these therapies has been confounded by a lack of knowledge about the identity of appropriate targets which can be harnessed to repair the lung, and the cellular and molecular factors which regulate their regenerative potential. While systematic analysis of lung development and cell lineage tracing studies in normal and perturbed animal models provides a framework for understanding the complex interplay of the multiple cell types, biomatrix elements and soluble and insoluble cytokines and factors that regulate lung structure and function, a reductionist approach is also required to analyze the organization of regenerative cells in the adult lung and identify the factors and molecular pathways which regulate their capacity to generate descendent lineages. In this review we describe recent progress in identifying and characterizing endogenous epithelial, mesenchymal and endothelial stem/progenitor cells in the adult lung using multiparameter cell separative strategies and functional in vitro clonogenic assays.
Longitudinal analysis of androgen deprivation of prostate cancer cells identifies pathways to androgen independence (2008)

These findings contribute greatly to our understanding of androgen-independent prostate cancer. The value of this longitudinal approach lies in the ability to examine gene expression changes throughout the adaptive response to androgen deprivation; it provides a more dynamic illustration of genes which contribute to disease progression in addition to specific genes which constitute an androgen-independent phenotype.
Rectifying Behavior of Electrically Aligned ZnO Nanorods (2003)

We report on the electrical alignment of ZnO nanorods and their electrical properties. The ZnO nanorods were wet-chemically synthesized, and their length and diameter were adjusted to about 200−300 nm and 15−30 nm, respectively. The nanorods were deposited onto electrode structures and directed into 200- to 800-nm-wide electrode gaps by using alternating electric fields at frequencies between 1 and 10 kHz and field strengths between 106 and 107 V/m. The nanorods align parallel to the electric field lines and make electrical contact with the gold electrodes. Clear photoresponse to 366-nm ultraviolet light irradiation was demonstrated. The current−voltage characteristics of the aligned rods are strongly nonlinear and asymmetrical, showing rectifying, diode-like behavior and asymmetry factors up to 25 at 3-V bias voltage.
Thrombspondin Acts via Integrin-associated Protein to Activate the Platelet Integrin αIIbβ3 (1997)

Integrin-associated protein (IAP or CD47) is a receptor for the cell/platelet-binding domain (CBD) of thrombospondin-1 (TS1), the most abundant protein of platelet alpha granules. Although it associates with alphaIIbbeta3, IAP has no known function in platelets. TS1, the CBD, and an IAP agonist peptide (4N1K) from the CBD of TS1 activate the platelet integrin alphaIIbbeta3, resulting in platelet spreading on immobilized fibrinogen, stimulation of platelet aggregation, and enhanced tyrosine phosphorylation of focal adhesion kinase. Furthermore, 4N1K peptide selectively stimulates the phosphorylation of LYN and SYK and their association with FAK. The phosphorylation of SYK is blocked by pertussis toxin, implicating a Gi-like heterotrimeric G protein. IAP solublized from membranes of unstimulated platelets binds specifically to an affinity column of 4N1K peptide. Both alphaIIb and beta3 integrin subunits and c-Src bind along with IAP. This complex of proteins is also detected with immunoprecipitation. Activation of platelets with the agonist peptide 4N1K results in the association of FAK with the IAP-alphaIIbbeta3 complex. Thus an important function of TS1 in platelets is that of a secreted costimulator of alphaIIbbeta3 whose unique properties result in its localization to the platelet surface and the fibrin clot.
Effect of Sodium Glucose Cotransporter 2 Inhibitors With Low SGLT2/SGLT1 Selectivity on Circulating Glucagon-Like Peptide 1 Levels in Type 2 Diabetes Mellitus (2017)

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1. Recent evidence shows that these SGLT2 inhibitors with low SGLT2/SGLT1 selectivity elevate the level of circulating glucagon like peptide-1 (GLP-1), an incretin hormone that promotes insulin secretion in pancreatic β cells. This effect probably occurs partly via inhibition of intestinal SGLT1, and the elevation of active GLP-1 levels is especially apparent when these drugs are co-administered with dipeptidyl peptidase 4 (DPP4) inhibitors. These findings suggest that a combination of canagliflozin or sotagliflozin and a DPP4 inhibitor can provide a beneficial effect associated with elevation of circulating active GLP-1 and may serve as a treatment for patients with type 2 diabetes.
Contact-activated Monocytes: Efficient Antigen Presenting Cells for the Stimulation of Antigen-specific T cells (2006)

Mature dendritic cells (DCs) are potent antigen presenting cells (APCs) that have been used in vaccine studies and adoptive immunotherapy protocols. For many clinical studies DCs are derived from monocytes in the presence of cytokines, which are expensive and often unavailable for clinical use. Here we describe a cytokine independent method for the differentiation of monocytes into APCs for the reactivation of antigen-specific memory T cells from both healthy donors and cancer patients. Contact activation of monocytes resulted in secretion of proinflammatory cytokines, such as IL-8, and increased cell surface expression of costimulatory molecules. To determine if activated monocytes (actMo) like DC can reactivate antigen-specific CTL, they were transduced with adenoviral vectors encoding the subdominant Epstein Barr virus antigens, latent membrane proteins (LMP) 1 and 2, which are expressed in Epstein Barr virus-positive malignancies. Stimulation of peripheral blood mononuclear cells with LMP1- and LMP2-expressing actMo activated LMP1- and LMP2-specific T cells, which could be further expanded with LMP1 or LMP2 expressing lymphoblastoid cell lines. The use of actMo as APCs simplifies the production/manufacture of antigen-specific T cells for clinical trials.
Microbial flora in the gastrointestinal tract abolishes cytostatic effects of α‐difluoromethylornithine in vivo (1989)

Although treatment with the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO) leads to depletion of intracellular polyamines and to related growth inhibition in vitro, its cytostatic effects in vivo are disappointing. This may be due to abolition of DFMO-induced growth inhibition by polyamines released during normal body cell turnover, to dietary polyamines, or to putrescine synthesized by the microbial flora in the GI tract. We studied selectively (aerobic) and totally (aerobic + anaerobic) GI tract-decontaminated LI210-bearing mice fed with 3 types of diet differing in their polyamine and carbohydrate residue contents and treated with combinations of intraperitoneal DFMO and oral deuterium-labelled putrescine. Our data show that, irrespective of diet type, total decontamination markedly potentiates the moderate tumor growth inhibition that is caused by DFMO alone. During total decontamination, growth-inhibited L1210 cells accumulate in the G0/G1 phase of the cell cycle. Although orally administered deuterium-labelled putrescine gave rise to deuterium labelling of L1210 putrescine, spermidine and spermine, the polyamine levels in our diets played only a minor role.
Newly Synthesized Glycoproteins in Plasma Membranes of Cells Transformed by SV40 and Its Gene A Function (1980)

SV40 temperature sensitive mutant transformed mouse cells synthesized different membrane glycoproteins at 5 to 10 hr after temperature shift and inhibition of DNA synthesis by cytosine arabinoside (Ara C) after temperature shift led to the alterations in the patterns of newly synthesized membrane glycoproteins analyzed by polyacrylamide gel electrophoresis.