gebhart/patrepeval huggingface dataset:
Transfection of single-stranded hepatitis A virus RNA activates MHC class I pathway (2002)

Although infection of single-stranded RNA viruses can enhance expression of major histocompatibility complex (MHC) class I genes, the mechanism underlying this process remains unclear. Recent studies have indicated that exposure of non-immune cells to double-stranded deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) of viral origin can directly increase the expression of MHC class I and related molecules without immune cell interaction. In this report, we show that transfection of single-stranded hepatitis A virus RNA into cultured hepatocytes results in the induction of genes for MHC class I, LMP2 and transporter for antigen processing (TAP1), in addition to the generation of viral proteins. We suggest that this stimulatory effect is due to the double-stranded RNA formed during replication of single-stranded viral RNA, and involves both double-stranded, RNA-dependent protein kinase PKR and the secretion of IFNbeta.
The glucocorticoid receptor signalling in breast cancer (2007)

Glucocorticoids are provided as co-medication with chemotherapy in breast cancer, albeit several lines of evidence indicate that their use may have diverse effects and in fact may inhibit chemosensitivity. The molecular basis of glucocorticoid-induced resistance to chemotherapy in breast cancer remains poorly defined. Recent researchers, in an attempt to clarify some aspects of the underlying pathways, provide convincing evidence that glucocorticoids induce effects that are dependent upon the glucocorticoid receptor -mediated transcriptional regulation of specific genes known to play key roles in cellular/tissue functions, including growth, apoptosis, differentiation, metastasis and cell survival. In this review, we focus on how glucocorticoid-induced chemoresistance in breast cancer is mediated by the glucocorticoid receptor, unraveling the molecular interplay of glucocorticoid receptor signaling with other signaling cascades prevalent in breast cancer. We also include a detailed description of glucocorticoid receptor structure and function, summarizing data gained during recent years into the mechanism(s) of the cross-talk between the glucocorticoid receptor and other signaling cascades and secondary messengers, via which glucocorticoids exert their pleiotropic effects.
Inhibition of Potentially Lethal Damage Recovery by Altered PH, Glucose Utilization and Proliferation in Plateau Growth Phase Human Glioma Cells (1994)

Recovery from potentially lethal damage (PLD) has been measured in plateau growth phase human glioblastoma cells (U-87MG) under four postirradiation medium conditions. Recovery was maximal in depleted medium at an acidic pH, conditions which inhibit cellular proliferation. Compared with this control, PLD recovery (PLDR) was increasingly inhibited by alkalization of the existing medium (to pH 7.4), exchanging the old medium with fresh medium-pH acidified (to pH 6.8), and exchanging the old medium with fresh medium-pH unaltered (pH 7.4), respectively. These three medium adjustments were made at the time of irradiation. Increased glucose utilization (glycolysis) was detected postirradiation in all three cases, while increased proliferation was detected only when fresh medium was exchanged for old medium. Thus inhibition of PLDR has been correlated with increased glycolysis and increased proliferation during the recovery period. When acting together, these two processes provided almost complete inhibition. This study was revealed that the degree of inhibition may be related to the amount of glycolysis and/or proliferation occurring during the recovery period. Examining, in vitro, the range of PLDR achieved by postirradiation manipulation of medium pH may provide some indication of the range in PLDR that may be expected in vivo. Our study demonstrates that the effect of pH on glycolysis and proliferation may be important when determining the ability of a particular cell type to recover from PLD.
Metal-Enhanced Fluorescence-Based RNA Sensing (2006)

In this communication, we present the proof-of-principle of a new RNA sensing technique, based on metal-enhanced fluorescence, which may improve the potential of solid substrate-based RNA capture assays. In this regard, the detection of RNA is accomplished by annealing a target RNA tagged with a fluorophore to a DNA anchor probe in a single step on a solid surface, where the fluorescence signal is enhanced by silver nanoparticles. Furthermore, the proposed method is highly amenable to high-throughput screening applications and is capable of detecting less than 25 fmol of RNA at a signal-to-noise ratio greater than 20, in several hours compared to that of reverse transcription-PCR at >24 h.
Two-step binding mechanism of fibrinogen to alpha IIb beta 3 integrin reconstituted into planar lipid bilayers. (1993)

The platelet integrin alpha IIb beta 3 binds to fibrinogen and thus mediates platelet aggregation after stimulation. This integrin was isolated from human platelets and reconstituted into lipid vesicles. As judged by electron microscopy the integrin incorporated adequately only into 1,2-dimyristoylglycero-3-phosphocholine/1,2-dimyristoylphosphatidy lglycerol vesicles after removal of the detergent by adsorption to Bio-Beads. These vesicles were then used to generate planar lipid bilayers. The binding of fluorochrome labeled fibrinogen or the peptide ligand Gly-Arg-Gly-Asp-Ser-Pro-Cys (GRGDSPC) was monitored by total internal reflection fluorescence microscopy and a solid phase binding assay. Analysis of the kinetics revealed fast reversible formation of a fibrinogen/integrin precomplex (KD = 50 nM) followed by formation of a stable irreversible complex. This transition was monitored by measuring the fraction of precomplex which could be dissociated by addition of excess Gly-Arg-Gly-Asp-Ser (GRGDS). For the peptide, the KD was 1200 nM, and the rates of association and dissociation were faster than the time resolution of the method. Similar KD values were found by inhibition of fibrinogen binding to alpha IIb beta 3 in the immobilized receptor assay. Since the binding of fibrinogen was irreversible, KD values were dependent on the time period between fibrinogen incubation and peptide addition. These and results by other authors point to the biological importance of the biphasic binding process of fibrinogen to its receptor on platelets.
AM video on fiber in CATV systems: need and implementation (1990)

Limitations of current CATV (cable television) system architecture are described. A hybrid optical fiber/coaxial cable architecture is introduced, and the performance levels necessary for the optical portions of that system are explored. Optical device performance is outlined as it applies to such a hybrid system, and various optical components with the potential to be used in such a system are examined. It is concluded that the hybrid fiber backbone/coaxial distribution architecture outlined meets a number of needs within the CATV industry. It provides a means of significantly improving the operation of CATV plant while laying the foundation of future evolution.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Super‐Hydrophobic and Super‐Oleophilic Coating Mesh Film for the Separation of Oil and Water (2004)

An example from nature: Analogous to the surface structure of the lotus leaf, the micro- and nanostructured rough surfaces of a teflon-coated mesh film engender it with both super-hydrophobic and super-oleophilic properties. The result is a variable film with contact angles of ≈150° for water and almost 0° for diesel oil, which makes it an ideal tool for the separation of oil and water (see figure).
IL-10 therapy in Crohn's disease: at the crossroads (2002)

Treatment of Crohn's disease with the anti-inflammatory cytokine interleukin 10

Interleukin 10 (IL-10) was initially discovered and isolated on the basis of its ability to suppress cytokine synthesis by Th1 helper cells. Macrophages and their secreted mediators are the primary target of IL-10. IL-10 downregulates expression of class II and B7 molecules, as well as IL-12 production, thus impairing the macrophage dependent stimulation of antigen reactive Th-1 cells.1

The important regulatory role of IL-10 in the gut became obvious when IL-10 deficient mice (IL-10−/−), generated by gene targeting, developed chronic enterocolitis.2 More interestingly, IL-10−/− mice kept under germfree conditions do not develop enterocolitis, which suggests that in the absence of the immunomodulatory effects of IL-10, an unrestricted intestinal inflammatory response develops towards normal enteric antigens. The observations in the IL-10−/− mice lay the foundation for administration of IL-10 in several animal models. The results of these studies clearly showed prevention of intestinal inflammation by IL-10, mainly by downregulation of an intestinal proinflammatory Th1 response. However, systemic IL-10 administration was successful only when administered prior to the initiation of colitis but was ineffective at reversing any established inflammation.3,4

Based …
Neuronal regeneration in a zebrafish model of adult brain injury (2011)

Neural stem cells in the subventricular zone (SVZ) of the adult mammalian forebrain are a potential source of neurons for neural tissue repair after brain insults such as ischemic stroke and traumatic brain injury (TBI). Recent studies show that neurogenesis in the ventricular zone (VZ) of the adult zebrafish telencephalon has features in common with neurogenesis in the adult mammalian SVZ. Here, we established a zebrafish model to study injury-induced neurogenesis in the adult brain. We show that the adult zebrafish brain possesses a remarkable capacity for neuronal regeneration. Telencephalon injury prompted the proliferation of neuronal precursor cells (NPCs) in the VZ of the injured hemisphere, compared with in the contralateral hemisphere. The distribution of NPCs, viewed by BrdU labeling and ngn1-promoter-driven GFP, suggested that they migrated laterally and reached the injury site via the subpallium and pallium. The number of NPCs reaching the injury site significantly decreased when the fish were treated with an inhibitor of γ-secretase, a component of the Notch signaling pathway, suggesting that injury-induced neurogenesis mechanisms are at least partly conserved between fish and mammals. The injury-induced NPCs differentiated into mature neurons in the regions surrounding the injury site within a week after the injury. Most of these cells expressed T-box brain protein (Tbr1), suggesting they had adopted the normal neuronal fate in this region. These results suggest that the telencephalic VZ contributes to neural tissue recovery following telencephalic injury in the adult zebrafish, and that the adult zebrafish is a useful model for regenerative medicine.
Standing-wave and RF penetration artifacts caused by elliptic geometry: an electrodynamic analysis of MRI (1998)

Motivated by the observation that the diagonal pattern of intensity nonuniformity usually associated with linearly polarized radio-frequency (RF) coils is often present in neurological scans using circularly polarized coils, a theoretical analysis has been conducted of the intensity nonuniformity inherent in imaging an elliptically shaped object using 1.5-T magnets and circularly polarized RF coils. This first principle analysis clarifies, for the general case of conducting objects, the relationship between the excitation field and the reception sensitivity of circularly and linearly polarized coils. The results, validated experimentally using a standard spin-echo imaging sequence and an in vivo B1 field mapping technique, are shown to be accurate to within 1%-2% root mean square, suggesting that these electromagnetic interactions with the object account for most of the intensity nonuniformity observed.
The glycogenolytic response to stimulation of the splanchnic nerves in adrenalectomized calves (1970)

1. The effects of stimulation of the peripheral ends of one or both splanchnic nerves have been investigated in adrenalectomized calves at different ages.2. During the first 24 hr after birth unilateral splanchnic nerve stimulation led to a prompt rise in the plasma glucose concentration and this response was more than doubled when both nerves were stimulated simultaneously. Under these latter conditions hyperglycaemia was found to be associated with a measurable loss of glycogen from the liver.3. Both the glycogenolytic and hyperglycaemic effects of splanchnic stimulation became more pronounced with age; at 5 weeks of age liver glycogen was depleted by approximately 2/3 and plasma glucose raised by about 200 mg/100 ml. after stimulation of the right splanchnic nerve for 9 min.4. Splanchnic stimulation also caused a rise in mean arterial blood pressure and haematocrit during the period of stimulation at all ages studied; the rise in haematocrit was greatest in the oldest animals.5. The hyperglycaemic response to splanchnic stimulation persisted after pancreatectomy and was also demonstrated in calves in which the whole of the portal effluent blood flow was collected during splanchnic stimulation. The plasma from blood collected in this way had no apparent hyperglycaemic effect when infused into a branch of the mesenteric vein in recipient calves.6. In adrenalectomized calves in which the liver had been partially denervated before stimulation both the hyperglycaemic and the glycogenolytic responses were substantially reduced, although the rise in haematocrit was unaffected, during stimulation of both splanchnic nerves.7. It is concluded that glycogenolysis occurs in the liver as a result of stimulation via the hepatic innervation in the new-born calf and that this response increases with age during the first few weeks after birth.
Protection of BALB/c Mice againstBrucella abortus544 Challenge by Vaccination with Bacterioferritin or P39 Recombinant Proteins with CpG Oligodeoxynucleotides as Adjuvant (2001)

The P39 and the bacterioferrin (BFR) antigens of Brucella melitensis 16M were previously identified as T dominant antigens able to induce both delayed-type hypersensivity in sensitized guinea pigs and in vitro gamma interferon (IFN-gamma) production by peripheral blood mononuclear cells from infected cattle. Here, we analyzed the potential for these antigens to function as a subunitary vaccine against Brucella abortus infection in BALB/c mice, and we characterized the humoral and cellular immune responses induced. Mice were injected with each of the recombinant proteins alone or adjuvanted with either CpG oligodeoxynucleotides (CpG ODN) or non-CpG ODN. Mice immunized with the recombinant antigens with CpG ODN were the only group demonstrating both significant IFN-gamma production and T-cell proliferation in response to either Brucella extract or to the respective antigen. The same conclusion holds true for the antibody response, which was only demonstrated in mice immunized with recombinant antigens mixed with CpG ODN. The antibody titers (both immunoglobulin G1 [IgG1] and IgG2a) induced by P39 immunization were higher than the titers induced by BFR (only IgG2a). Using a B. abortus 544 challenge, the level of protection was analyzed and compared to the protection conferred by one immunization with the vaccine strain B19. Immunization with P39 and CpG ODN gave a level of protection comparable to the one conferred by B19 at 4 weeks postchallenge, and the mice were still significantly protected at 8 weeks postchallenge, although to a lesser extent than the B19-vaccinated group. Intriguingly, no protection was detected after BFR vaccination. All other groups did not demonstrate any protection.
Nonsense-mediated mRNA decay: from mechanistic insights to impacts on human health (2012)

Cells are able to recognize and degrade aberrant transcripts in order to self-protect from potentially toxic proteins. Various pathways detect aberrant RNAs in the cytoplasm and are dependent on translation. One of these pathways is the nonsense-mediated RNA decay (NMD). NMD is a surveillance mechanism that degrades transcripts containing nonsense mutations, preventing the translation of possibly harmful truncated proteins. For example, the degradation of a nonsense harming β-globin allele renders normal phenotypes. On the other hand, regulating NMD is also important in those cases when the produced aberrant protein is better than having no protein, as it has been shown for cystic fibrosis. These findings reflect the important role for NMD in human health. In addition, NMD controls the levels of physiologic transcripts, which defines this pathway as a novel gene expression regulator, with huge impact on homeostasis, cell growth and development. While the mechanistic details of NMD are being gradually understood, the physiological role of this RNA surveillance pathway still remains largely unknown. This is a brief and simplified review on various aspects of NMD, such as the nature of the NMD targets, the mechanism of target degradation and the links between NMD and cell growth, animal development and diseases.
Age‐related decline in chondrocyte response to insulin‐like growth factor‐I: The role of growth factor binding proteins (1997)

The synthetic activity of chondrocytes in articular cartilage declines with age, possibly as a result of decreased sensitivity to anabolic growth factors such as insulin-like growth factor-I. The sensitivity of these cells to insulin-like growth factor-I is regulated, in part, by the synthesis of insulin-like growth factor-I binding proteins. We hypothesized that, as cartilage ages, an increase in the expression of these binding proteins suppresses the synthetic response of chondrocytes to insulin-like growth factor-I. To test this hypothesis, we measured proteoglycan synthesis (incorporation of [35S]sulfate per cell) in alginate cultures of chondrocytes from the articular cartilage of 1, 3, 12, and 24-month-old rats. A dose-response to insulin-like growth factor-I was determined for cells from each age group; incorporation of [35S]sulfate per cell declined with age, regardless of the dose. The sharpest decline was found between cells from the 1 and 3-month-old groups. Using the Western ligand blot technique, we then compared the expression of insulin-like growth factor-I binding protein in chondrocytes from the 1 and 3-month-old rats and found that it was increased in the cells from the older animals. Recombinant insulin-like growth factor-3, when added to the cell cultures of the 1-month-old rats, inhibited incorporation of [35S]sulfate and blocked responses to insulin-like growth factor-I. These findings suggest that the age-related decline in the synthetic response of chondrocytes to insulin-like growth factor-I results, at least in part, from increased expression of insulin-like growth factor binding protein.
Activation of lysine 2,3-aminomutase by S-adenosylmethionine. (1990)

Lysine 2,3-aminomutase, which catalyzes the interconversion of L-lysine and L-beta-lysine, is S-adenosyl-methionine-dependent, and the adenosyl-C-5' methylene group of this coenzyme mediates the transfer of hydrogen from C-3 of lysine to C-2 of beta-lysine. We here report experiments that address the mechanism by which S-adenosylmethionine activates lysine 2,3-aminomutase. We also describe an updated and improved purification procedure that produces enzyme with a specific activity substantially higher than that previously reported. Activation of the enzyme by less than 1 mol of S-adenosyl[1-14C]methionine/mol of subunits in the presence of lysine leads to the production of [14C] methionine in a kinetically biphasic process. After 1.8 min at 30 degrees C, 10% of the 14C is reisolated as [14C] methionine, and the cleavage increases to 19% after 10 min and to 51% after 40 min. Similar experiments with S-[8-14C]adenosylmethionine produce 5'-deoxy[14C]adenosine in amounts similar to the formation of methionine. The major radioactive products isolated in each case are [14C]methionine or 5'-deoxy[14C]adenosine, respectively, and unchanged 14C-labeled S-adenosylmethionine. These experiments support the hypothesis that activation of lysine 2,3-aminomutase involves a transfer of the 5'-deoxyadenosyl moiety from S-adenosylmethionine to another species associated with the enzyme, presumably another cofactor, to form an adenosyl cofactor that functions as the proximal, hydrogen abstracting species in the mechanism.
Identification and characterization of a hepatitis delta virus RNA transcriptional promoter (1996)

Transcription and replication of hepatitis delta virus (HDV) RNA are performed by the cellular enzyme RNA polymerase II (Pol II). As DNA is the normal template for Pol II, the enzyme must undergo template switching. The mechanism for this is unknown, but since HDV RNA can form a rod-like molecule by extensive intramolecular base pairing, it has been suggested that a double-stranded region(s) of HDV RNA serves as a recognition site for Pol II. A bidirectional promoter has been identified previously on HDV cDNA (T. B. Macnaughton, M. R. Beard, M. Chao, E. J. Gowans, and M. M. C. Lai, Virology 196:629-636, 1993). In the present study, genomic RNA corresponding to this region was able to direct the synthesis of antigenomic RNA in a nuclear extract transcription reaction, whereas genomic RNA species containing a mutation that resulted in a replication-defective phenotype were unable to do so. Thus, this region, the location of which is defined as nucleotides 1608 to 1669 on the basis of a highly conserved structure, represents a RNA-RNA promoter. Computer analysis of the RNA secondary structure predicted that the promoter contains two bulge regions in a stem-loop structure which encompasses a GC-rich motif. This predicted model was confirmed by enzyme digestion and primer extension analysis. The promoter is located at one end of the rod and has some homology with the simian virus 40 late promoter. A number of other mutations were introduced within this region, and expression plasmids were constructed to examine the effects of mutations in the promoter on HDV replication. Disruption of the overall secondary structure, particularly the bulge regions, totally inhibited HDV RNA replication.
Dynamic changes in cytokine secretion by stromal cells during prolonged maintenance under protein‐free conditions (1992)

Stromal cells of bone marrow origin produce a variety of known cytokines and some factors exhibiting apparently new biological activities. Several of these were identified by the study of cell to cell interactions and were not found in detectable amounts in media conditioned by the cells. We describe here a culture system that enables the release of stromal cytokines into medium free of any added proteins and supplemented with peptides from casein hydrolysate (0.1%). The absence of serum proteins allows extensive concentration and monitoring of activities that are otherwise undetectable. Stromal cells of the MBA-2.1 clonal cell line were seeded in a stationary bed reactor packed with a carrier of non-woven fabric matrix. After a proliferation phase with serum containing medium, the cells were maintained for over 10 months in protein-free medium. Throughout this extended incubation in the absence of serum or serum replacing proteins, stromal cells retained their viability and continuously released transforming growth factor-beta (TGF-beta), macrophage-colony stimulating factor (M-CSF) and restrictin-P, a cytotoxic factor that specifically arrested the growth of plasmacytoma cells. In addition, interleukin-6 (IL-6) was first undetectable, and later in culture its titer reached a maximum of 180,000 international units (IU)/ml. Concomitantly, the production of restrictin-P diminished and reached its lowest levels at the end of 10 months. The results may imply a possible causal relationship between the expression of IL-6 and restrictin-P, since no similarly significant changes were observed in the titers of M-CSF and TGF-beta. This novel bioreactor system may be adaptable for efficient production of different cytokines under absolute serum-free conditions.