gebhart/patrepeval huggingface dataset:
Targeted overexpression of protein kinase C β2 isoform in myocardium causes cardiomyopathy (1997)

Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCbeta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCbeta2 isoform in the myocardium. These mice overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCbeta2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.
The Family of Guanylyl Cyclase Receptors and Their Ligands (1994)

IN 1963, shortly after the discovery of cAMP (1–5), Ashman et al. (6) identified cyclic-GMP (cGMP) in rat urine. Reports soon followed showing that various agents including neurotransmitters and hormones elevated cGMP concentrations in many different cells (for review see Ref. 7). In 1969, three laboratories discovered the enzyme, guanylyl cyclase (8–11). Initial expectations that the enzyme would be regulated in much the same manner as its already exciting sibling, adenylyl cyclase, met with immediate problems. These included the localization of guanylyl cyclase to both the particulate and soluble fractions of cell homogenates, and multiple experimental failures to activate the enzyme in broken cell preparations by agents known to elevate cGMP levels in intact cells. As a consequence, much of the earliest work on guanylyl cyclase concentrated on descriptive features of the soluble and particulate forms. In the mid-1970s, three studies (12–14) provided the first evidence that guanylyl cyclase activities present in the soluble and particulate fractions of cell homogenates appeared to be due to different proteins.
A direct selection strategy for shotgun cloning and sequencing in the bacteriophage M13 (1994)

A new cloning strategy is described which utilizes direct selection of recombinants for shotgun sequencing in the filamentous bacteriophage M13. Direct selection is accomplished by insertional inactivation of the M13 gene X protein, a powerful inhibitor of phage-specific DNA synthesis when overproduced. An extra copy of gene X was inserted into the intergenic region of M13 and placed under the control of the bacteriophage T7 gene 10 promoter and RBS. Random fragments are cloned into the EcoRV cloning site of the new gene X cistron and recombinants are selected in an E. coli male strain producing T7 RNA polymerase. Cloning efficiencies obtained with M13-100 or phosphatase-treated M13mp19 vector are comparable. The direct selection capability of M13-100 was demonstrated to have the following advantages: (a) consistently achieved high ratios of recombinants to religated vector in the libraries, averaging about 500:1 (0.2% background), and (b) the elimination of the need for phosphatase treatment of the vector to reduce background. The direct selection strategy significantly improves the efficiency of shotgun library construction in M13, and should therefore facilitate the cloning aspects of large scale sequencing projects.
Infection of polarized MDCK cells with herpes simplex virus 1: two asymmetrically distributed cell receptors interact with different viral proteins. (1991)

Herpes simplex virus 1 attaches to at least two cell surface receptors. In polarized epithelial (Madin-Darby canine kidney; MDCK) cells one receptor is located in the apical surface and attachment to the cells requires the presence of glycoprotein C in the virus. The second receptor is located in the basal surface and does not require the presence of glycoprotein C. Exposure of MDCK cells at either the apical or basal surface to wild-type virus yields plaques and viral products whereas infection by a glycoprotein C-negative mutant yields identical results only after exposure of MDCK cells to virus at the basal surface. Multiple receptors for viral entry into cells expand the host range of the virus. The observation that glycoprotein C-negative mutants are infectious in many nonpolarized cell lines suggests that cells in culture may express more than one receptor and explains why genes that specify the viral proteins that recognize redundant receptors, like glycoprotein C, are expendable.
Mechanically driven luminescence in a ZnS:Cu-PDMS composite (2016)

The conventional mechanoluminescence (ML) mechanism of phosphors such as SrAl2O4:Eu and ZnS:Mn is known to utilize carrier trapping at shallow traps followed by stress (or strain)-induced detrapping, which leads to activator recombination in association with local piezoelectric fields. However, such a conventional ML mechanism was found to be invalid for the ZnS:Cu-embedded polydimethylsiloxane (PDMS) composite, due to the absence of luminescence with a rigid matrix and a negligibly small value of the piezoelectric coefficient (d33) of the composite. An alternative mechanism, namely, the triboelectricity-induced luminescence has been proposed for the mechanically driven luminescence of a ZnS:Cu-PDMS composite.
Novel human embryonic stem cell lines C612 and C910 (2009)

Novel human embryonal stem cell lines C612 and C910 have been established from hatching blastocytes. Cells were cultivated in mTeST medium on mouse fibroblast feeder-layers. They express common pluripotent markers such as alkaline phosphatase, Oct 3/4, SEEA-4, Nanog, Rex1. Immunophenotyping of these cells by flow cytometry revealed expression of CD90 (Thy-1) and CD117 (c-kit) antigens and weak or no expression of CD13, CD34, CD45, CD130, HLA class I and HLA class II antigens. This pattern of surface antigen expression is common for human embryonic stem cells. G-banding assay of C612 and C910 metaphase plates showed that karyotypic structure of these cells was normal both in chromosome number and structure. The cells are pluripotent because of their capability to generate embryoid bodies, undergo spontaneous differentiation and express markers of all germ layers: nestin, keratin, vimentin (ectoderm), alpha-fetoprotein (entoderm), and muscle alpha-actinin (mesoderm). Thus, C612 and C910 cells have all attributes of typical human embryonic stem cells (diploid, capable of self-renewal, express pluripotent markers and differentiate into three germ layers) and may be of potential use for fundamental and regenerative medicine researches.
T-cell Receptor Sequencing Reveals the Clonal Diversity and Overlap of Colonic Effector and FOXP3+ T Cells in Ulcerative Colitis (2014)

Thus, at steady state, only a minority of FOXP3, and particularly Helios, T cells share a T-cell receptor sequence with FOXP3 effector populations in the colon LP, even in UC, revealing distinct clonal origins for LP regulatory T cell and effector T cells in humans.
Activation of protein kinase B and induction of adipogenesis by insulin in 3T3-L1 preadipocytes: contribution of phosphoinositide-3,4,5-trisphosphate versus phosphoinositide-3,4-bisphosphate. (1999)

Ectopic expression of activated protein kinase B (PKB) induces the differentiation of confluent 3T3-L1 preadipocytes into adipocytes. PKB is regulated by the lipid products of phosphoinositide 3-kinase (PI 3-kinase), phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2], and phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P3]. However, the relative contribution of each 3-phosphorylated phosphoinositide species in activating PKB remains unclear. Treatment of intact 3T3-L1 preadipocytes with synthetic 3-phosphorylated phosphoinositides revealed that only PI(3,4)P2 stimulated PKB activity. PKB was also activated by insulin, in a dose- and time-dependent manner. This activation was associated with an isolated rise in PI(3,4,5)P3, without any detectable change in PI(3,4)P2, demonstrating that this lipid was sufficient to activate PKB. Wortmannin and LY294002, inhibitors of PI 3-kinase, reduced insulin-dependent activation of PKB, whereas rapamycin, an inhibitor of p70 S6 kinase, had no effect. Platelet-derived growth factor (PDGF), which is not adipogenic, stimulated the production of both 3-phosphorylated phosphoinositide species, and this was associated with a greater activation of PKB than that observed with insulin. A low dose of PDGF (1 ng/ml), which increased the production of only PI(3,4,5)P3 and mirrored the insulin effect, was unable to induce adipocyte differentiation. In summary, insulin and PDGF differ with respect to the accumulation of 3-phosphorylated phosphoinositides and to PKB activation in 3T3-L1 preadipocytes, but these responses do not themselves explain why insulin, but not PDGF, is adipogenic.
Nitric oxide and cGMP can produce either synaptic depression or potentiation depending on the frequency of presynaptic stimulation in the hippocampus (1994)

Nitric oxide (NO) has been suggested to play the role of retrograde messenger during long-term potentiation (LTP) in hippocampus. In support of this idea, NO induces LTP when paired with a weak tetanus (50 Hz). An additional criterion that has been proposed for NO being a retrograde messenger is that it should also elicit long-lasting enhancement when paired with low-frequency stimulation of the presynaptic fibers. In the present study, we have tested this prediction. We find that NO produces long-lasting depression rather than potentiation when paired with low-frequency stimulation (0.25 Hz). A similar long-lasting depression is produced by 8-Br-cGMP, a cGMP analog, suggesting that NO may produce its effect by activating soluble guanylyl cyclase. These results demonstrate that NO and cGMP modulate synaptic transmission in the hippocampus by frequency-dependent mechanisms, and suggest that NO is most suitable as a retrograde messenger for LTP when the presynaptic neuron fires at high frequencies. By contrast, carbon monoxide (CO) elicits long lasting enhancement at both low and high frequencies.
Relationship Between Values of Bioelectrical Impedance and Creatinine Clearance (1990)

This investigation was conducted to determine if measurements of bioelectrical impedance in conjunction with serum creatinine concentrations are useful in predicting creatinine clearance. Twenty-eight healthy volunteers between 23 and 50 years of age followed an individualized protein diet to provide 1.2 g protein/kg/day for 3 consecutive days. At the beginning of day 3, a 24-hour urine collection was initiated. At the midpoint of urine collection, bioelectrical impedance measurements of resistance and reactance were taken, together with a single blood sample for assessment of serum creatinine concentration. Multiple linear regression techniques were used to identify significant values for predicting creatinine clearance. Resistance and serum creatinine concentration were identified as significant predictors. The measured creatinine clearance was compared to that predicted by the impedance-derived model that we developed, as well as other established estimation methods. Mean absolute prediction errors in creatinine clearance using this model were significantly lower than those obtained using four empiric methods. Bioelectrical impedance may provide a noninvasive, quick, and accurate method for predicting creatinine clearance from serum creatinine concentration values.
Use of Microcontact Printing for Generating Selectively Grown Films of Poly(p-phenylene vinylene) and Parylenes Prepared by Chemical Vapor Deposition (2000)

Several non-photolithographic methods for growing patterned films of parylene-based polymers prepared by chemical vapor deposition are presented. These patterns were generated using transition metals and metal salts known to inhibit polymer deposition, in combination with alkanethiols deposited by microcontact printing. By patterning the alkanethiols on gold or silver surfaces, well-defined selectively grown structures of vapor-deposited parylene-N and parylene-C were realized, with lateral dimensions ranging from 1.5 to 35 μm. Using carboxylic acid-terminated alkanethiols deposited by microcontact printing to define regions of iron salt exposure on the surface, selectively grown films of poly(p-phenylene vinylene) were generated, with features having lateral dimensions of 12.5 μm separated by 2.5 μm, and thicknesses of 750 Å. The structures fabricated with this approach have dimensions relevant to applications in microelectromechanical systems and polymer-based displays.
Class Effect of Erythropoietin Therapy on Hemoglobin A1c in a Patient with Diabetes Mellitus and Chronic Kidney Disease Not Undergoing Hemodialysis (2009)

In patients with diabetes mellitus, hemoglobin A(1c) (A1C) is commonly interpreted as a measure of long-term glycemic control, reflecting a mean glucose level over the previous 2-3 months. Although some reports suggest that treatment with recombinant erythropoietin may affect A1C values in patients undergoing hemodialysis, we know of no evidence to support this interaction in patients with chronic renal insufficiency who are not undergoing hemodialysis. In addition, we know of no evidence specific to the treatment effect of epoetin alfa and/or darbepoetin alfa on A1C. We describe a 64-year-old man with diabetes, chronic kidney disease, and anemia who was treated consecutively with epoetin alfa and darbepoetin alfa and experienced a temporal reduction in A1C level to a nadir of 4.4%. Throughout approximately 3 years of treatment with these erythropoietin analogs, the patient's total daily dose of insulin was reduced in response to his decreasing A1C values, despite elevated blood glucose levels and the absence of patient-reported hypoglycemic events. Five months after the patient's erythropoietin therapy was discontinued, his A1C value increased to 8.8%, leading us to conclude that management of the insulin dose may have been different without the falsely lowered A1C levels. Use of the Naranjo adverse drug reaction probability scale indicated a probable association between this patient's reduced A1C levels and erythropoietin therapy. This case demonstrates that both epoetin alfa and darbepoetin alfa may artificially lower A1C levels in a patient with diabetes who is not undergoing dialysis, and therefore this finding can be interpreted as a class effect. Clinicians should be aware of factors that affect A1C values, specifically erythrocyte life span. In patients receiving erythropoietin, therapeutic decisions should be based on A1C and glucose levels, as well as patient symptoms suggestive of hypo- or hyperglycemia, to avoid therapy changes that could complicate disease management.
Closely related families of genes code for the α and α‘ subunits of the soybean 7S storage protein complex (1982)

Nineteen cloned cDNAs encoding the alpha and alpha'-subunits of the 7S seed storage protein in the soybean, Glycine max, have been isolated from a recombinant cDNA library constructed with mRNA from maturing seeds. In addition, a gene encoding an alpha'-subunit has been isolated from a recombinant Charon 4A phage library containing genomic Glycine max DNA. The cloned DNAs have been divided, on the basis of their endonuclease sites, into two main classes of sequences which differ in approximately 6% of their nucleotides. Whereas the proteins encoded within each DNA class are nearly identical, the proteins encoded by the two different classes of soybean DNAs are distinct and correspond to alpha and alpha'-subunits. Thus, the alpha and alpha'-subunits are coded for by two closely related multigene families. The amino acid differences in the portions of the alpha and alpha'-subunits presented in this paper occur primarily near the carboxyl-terminus. The 3' noncoding nucleotides of the cloned alpha and alpha'-subunit DNAs are more highly conserved than are the coding nucleotides. This conservation suggests that the 3' untranslated sequences of the alpha and alpha'-subunit mRNAs are functional in the expression of the alpha and alpha'-subunit proteins or in the stabilization of the 7S subunit mRNAs.
Physiological and Pharmacological Regulation of Prostaglandin and Leukotriene Production by Macrophages (1984)

The synthesis and secretion of prostaglandins and leukotrienes by mouse peritoneal macrophages is under several regulatory controls. Arachidonic acid must first be released from phospholipid stores by the action of phospholipases. Macrophages have the capacity to deacylate arachidonic acid directly from the SN2 position of phospholipids via the action of a phospholipase A2. In addition, these cells contain a phospholipase C capable of removing inositol-phosphate from phosphatidylinositol generating diacylglycerol. Another enzyme, diacylglycerol lipase is present to then generate arachidonic acid. The free arachidonic acid then enters the cyclooxygenase pathway to generate prostaglandins, the lipoxygenase pathway to generate leukotrienes or both pathways. The nature of the inflammatory stimulus added to these cells determines which of the above pathways become operative. Zymosan and the Ca++ ionophore, A23187 stimulate the synthesis of both prostaglandins and leukotrienes whereas phorbol myristate acetate and lipopolysaccharide induce only the synthesis of prostaglandins. In addition, the synthesis of these two products by macrophages can be regulated by certain antiinflammatory compounds. Indomethacin, aspirin, ibuprofen and benoxaprofen are only inhibitors of the prostaglandin pathway, whereas BW755C, 5,8,11-ETYA, NDGA and sulindac sulfide (high doses) are inhibitors of the synthesis of both prostaglandins and leukotrienes. Dapsone, an effective drug for leprosy, also inhibits the synthesis of both of these products.
The Macrophage Galactose-Type C-Type Lectin (MGL) Modulates Regulatory T Cell Functions (2015)

Regulatory T cells (Tregs) are physiologically designed to prevent autoimmune disease and maintain self-tolerance. In tumour microenvironments, their presence is related to a poor prognosis, and they influence the therapeutic outcome due to their capacity to suppress the immune response by cell-cell contact and to release immunosuppressive cytokines. In this study, we demonstrate that Treg immunosuppressive activity can be modulated by the cross-linking between the CD45RA expressed by Tregs and the C-type lectin MGL. This specific interaction strongly decreases the im-munosuppressive activity of Tregs, restoring the proliferative capacity of co-cultured T lymphocytes. This effect can be attributed to changes in CD45RA and TCR signalling through the inhibition of Lck and inactivation of Zap-70, an increase in the Foxp3 methylation status and, ultimately, the reduced production of suppressive cytokines. These results indicate a role of MGL as an immunomodulator within the tumour microenvironment interfering with Treg functions, suggesting its possible use in the design of anticancer vaccines.
Diseases Tracked by Using Google Trends, Spain (2009)

To the Editor: We read the article by Pelat et al. (1) with great interest and decided to explore whether this tool could be applicable for non-English and non-French speaking countries and, more specifically, for Spain. We compared the Google queries related to influenza-like illness (ILI) and chickenpox described by Pelat et al. (1), and constructed additional queries with symptoms and conditions frequently associated with ILI.

The weekly queries from January 2004 through February 2009 were downloaded from Google Insights for Search (2). We studied the correlation (Spearman ρ) of these queries with the data from the national reporting of notifiable diseases, available from the Spanish National Epidemiology Center website (3), assuming a maximum difference of 4 weeks.

The queries for gripe (Spanish for influenza) showed a maximum correlation (ρ = 0.70) 2 weeks before the declared ILI (DILI). When excluding the terms for aviar (avian) and vacuna (vaccine), the correlation peak (ρ = 0.81) was likewise observable 2 weeks before the DILI. The maximum correlation observed for symptom queries was for tos (Spanish for cough) 2 weeks before the DILI (ρ = 0.74); for conditions associated with influenza the correlation was for neumonia (Spanish for pneumonia, accented or unaccented) 2 weeks after the DILI (ρ = 0.84). The queries for varicela (Spanish for chickenpox) showed a maximum correlation (ρ = 0.96) 1 week after the declared illness, as observed by Pelat et al (1).

In conclusion, our study points out the utility of Internet queries for the surveillance of ILI and chickenpox in Spain. In the case of ILI, this information can be used as an early warning tool used complementarily to standard surveillance systems. More detailed studies are necessary regarding the usefulness and limitations of this tool in Spain, as well as in other contexts.
Prognosis in children with metastatic rhabdomyosarcoma (1977)

Distant metastases were documented in 83 of 161 children with rhabdomyosarcoma seen between 1953 and 1974. Of these, 31 had metastases at diagnosis (Group IV) and 7 were noted to have metastases only at autopsy. Only 6 are living with no evidence of disease activity at 6, 20, 77, 85, 105, and 112 months from time of metastasis. One child is living with disease at 98 months. Late deaths occurred in 2 at 31 and 41 months after metastasis. Sixty-four of the 66 deaths occurred within 24 months. The median durations of life after metastasis were less than 9 months in Groups I and II patients, less than 6 months in Group III patients, and about 12 months in 31 Group IV patients. The median time to metastasis in Groups I, II, and III patients was 9 months.
Differential expression of the two VEGF receptors flt and KDR in placenta and vascular endothelial cells (1994)

Vascular endothelial growth factor (VEGF) is a newly identified growth and permeability factor with a unique specificity for endothelial cells. Recently the flt-encoded tyrosine kinase was characterized as a receptor for VEGF. A novel tyrosine kinase receptor encoded by the KDR gene was also found to bind VEGF with high affinity when expressed in CMT-3 cells. Screening for flt and KDR expression in a variety of species and tissue-derived endothelial cells demonstrates that flt is predominantly expressed in human placenta and human vascular endothelial cells. Placenta growth factor (PIGF), a growth factor significantly related to VEGF, is coexpressed with flt in placenta and human vascular endothelial cells. KDR is more widely distributed and expressed in all vessel-derived endothelial cells. These data demonstrate that cultured human endothelial cells isolated from different tissues express both VEGF receptors in relative high levels and, additionally, that all investigated nonhuman endothelial cells in culture are also positive for KDR gene expression.