gebhart/patrepeval huggingface dataset:
In vivo Charakterisierung der 4-Cumarat:CoA Ligase-Familie in Arabidopsis thaliana (2003)

Ziel des Projekts war die Aufschlüsselung der in vivo-Funktionen der drei bekannten A. thaliana 4-Cumarat:CoA Ligasen. In silico Untersuchungen führten zur Entdeckung einer weiteren, wahtscheinlich letzten Isoform, At4CL4. Nach phylogenetischen und genomischen Analysen konnte At4CL4 den Klasse I-4CLs zugeordnet werden und ein Modell wurde vorgeschlagen, das die Evolution der At4CL-Familie beschreibt. At4CL4 wurde heterolog exprimiert und enzymkinetisch als bona fide 4CL charakterisiert mit der besonderen Fähigkeit in vitro Sinapinsäure zu aktivieren. Der At4CL4-katalysierten Aktivierung von Sinpinsäure bzw. Ferulasäure könnte eine Rolle im Stoffwechselweg zu den Sinpat-Derivaten oder Ligninvorstufen zukommen. Auf RT-PCR Ebene wurde die mRNA-Akkumulation der At4CLs untersucht. At4CL4 zeigte ein Muster grundsätzlich ähnlich dem der At4CL1 und der At4CL2 Dieses lässt eine in vivo Funktion der At4CL4 assoziiert mit der Synthese von Ligninvorstufen und anderen phenolischen Verbindungen erwarten. Neben der bereits existierenden At4CL1-Nullmutante wurde zu jedem weiteren Mitglied der At4CL-Familie mindestens eine weitere Linie isoliert, molekularbiologisch und biochemisch charakterisiert. In methanolischen Extrakten löslicher Sekundärmetabolite aus Wurzeln der At4CL1 Mutante wurde Akkumulation einer Verbindung mit einem UV-Spektrum ähnlich dem des Cumarins nachgewiesen In den HPLC-Profilen der At4CL3-Nullmutante wurde die Reduktion, nicht aber vollständiges Fehlen von Flavonoiden nachgewiesen. Die Ausprägung des At4CL3-Nullmutanten-Phänotyps war in verschiedenen Organen und Entwicklungsstufen unterschiedlich stark. Auch konnte keine UV- induzierbare Akkumulation von Flavonoiden in der At4CL3-Nullmutante gezeigt werden. Eine Funktion der At4CL3 kann daher in in der Aktivierung von Flavonoid-Vorstufen in jungen Pflanzen und nach UV-Perzeption bestehen. Um die funktionellen Redundanzen zu überwinden, wurden multiple Nullmutanten der At4CLs mit Mutanten der Gene AtCHS und AtF5H generiert, um weitere strategische Punkte des Metabolitenflusses abzudecken. Morphologische und biochemische Charakterisierung ausgewählter Mutanten zeigte, dass ein homozygoter Defekt von At4CL1 und At4CL2 zum Stagnieren der pflanzlichen Entwicklung im Alter von 5-6 Wochen führte. In HPLC-Profilen konnte hier die spezifische Akkumulation von drei Verbindungen nachgewiesen werden, die vermutlich 4-Cumarat- und Ferulat-Derivate darstellen. Daraus wurde geschlossen, dass die Funktionen von At4CL1 und At4CL2 in der Synthese von Ligninvorstufen und weiteren phenolischen Verbindungen der späten Entwicklungsstadien bestehen.
Exposure of cryptic epitopes on transthyretin only in amyloid and in amyloidogenic mutants (1999)

The structural requirements for generation of amyloid from the plasma protein transthyretin (TTR) are not known, although it is assumed that TTR is partly misfolded in amyloid. In a search for structural determinants important for amyloid formation, we generated a TTR mutant with high potential to form amyloid. We demonstrated that the mutant represents an intermediate in a series of conformational changes leading to amyloid. Two monoclonal antibodies were generated against this mutant; each displayed affinity to ex vivo TTR and TTR mutants with amyloidogenic folding but not to wild-type TTR or mutants exhibiting the wild-type fold. Two cryptic epitopes were mapped to a domain of TTR, where most mutations associated with amyloidosis occur and which we propose is displaced at the initial phase of amyloid formation, opening up new surfaces necessary for autoaggregation of TTR monomers. The results provide direct biochemical evidence for structural changes in an amyloidogenic intermediate of TTR.
Interleukin-10 Increases Th1 Cytokine Production and Cytotoxic Potential in Human Papillomavirus-Specific CD8+Cytotoxic T Lymphocytes (2000)

Interleukin-10 (IL-10) is widely known as an immunosuppressive cytokine by virtue of its ability to inhibit macrophage-dependent antigen presentation, T-cell proliferation, and Th1 cytokine secretion. However, several studies have challenged the perception of IL-10 solely as an immunosuppressive cytokine. As part of an investigation on potentiation of the cytotoxic activity of human papillomavirus E7-specific CD8(+) cytotoxic T lymphocytes (CTL) for adoptive transfusions to cervical cancer patients, we found that IL-10 in combination with IL-2, unlike several other combinations, including IL-2 with IL-12, gamma interferon (IFN-gamma), tumor necrosis factor alpha, and transforming growth factor beta, was able to consistently increase cytotoxicity. This augmentation in cytotoxic activity correlated with a significant increase in the cytoplasmic accumulation of perforin as detected by fluorescence-activated cell sorter. Surface expression of both the alpha and beta chains of the CD8 heterodimeric coreceptor and CD56 molecules was increased by exposure of CTL to IL-10. More importantly, we found that administration of IL-10 in combination with IL-2 after antigen stimulation consistently increased the intracellular expression of Th1 cytokines (i.e., IFN-gamma and IL-2) compared to results for control CD8(+) T cells cultured in IL-2 alone. In kinetic studies, proliferation, intracellular perforin levels, cytotoxic activity, and IFN-gamma expression were consistently elevated in CTL cultures containing IL-10 compared to control cultures, both at early and late time points following stimulation. In contrast, intracellular IL-2 expression was consistently increased only at early time points following stimulation with autologous tumor cells or solid-phase anti-CD3 antibody. Taken together, these data support the use of IL-10 in combination with IL-2 for the in vitro expansion and potentiation of tumor-specific CTL for clinical use in the therapy of cancer.
The Human Transient Receptor Potential Vanilloid Type 6 Distal Promoter Contains Multiple Vitamin D Receptor Binding Sites that Mediate Activation by 1,25-Dihydroxyvitamin D3 in Intestinal Cells (2006)

Transient receptor potential vanilloid type 6 (TRPV6) (ECAC2, CaT1) is the major ion channel in intestinal epithelial cell membranes responsible for calcium entry. Its expression is actively regulated at the transcriptional level by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. In this report, we identify mechanisms integral to the regulation of TRPV6 by 1,25-(OH)2D3. Based upon the hormonal responsiveness of a 7-kb TRPV6 promoter fragment in intestinal cell lines, we used a chromatin immunoprecipitation (ChIP) scanning method to search for possible vitamin D receptor (VDR) and retinoid X receptor (RXR) regulatory regions within the TRPV6 locus. VDR/RXR binding was broad, ranging from -1.2 to -5.5 kb relative to the start site of TRPV6 transcription. These results were consistent with an in silico analysis that revealed putative regulatory elements (VDREs) located at -1.2, -2.1, -3.5, -4.3, and -5.5 kb. Despite the ChIP analyses, only regions of the TRPV6 gene that contained putative elements at -2.1 and -4.3 kb transferred 1,25-(OH)2D3 response to a heterologous promoter. Further study revealed that each of these two active regions contained composite VDREs comprised of two separate regulatory elements. Mutagenesis of the VDREs within the -2.1- and -4.3-kb region and the VDRE at -1.2 kb abrogated all response to 1,25-(OH)2D3 when examined within the natural TRPV6 promoter. A final ChIP assay revealed that VDR/RXR heterodimer binding to the TRPV6 gene was accompanied by both the recruitment of steroid receptor coactivator 1 as well as a broad change in histone 4 acetylation. These studies identify a mechanism by which 1,25-(OH)2D3 regulates the expression of TRPV6 in human intestinal cells.
A variant of human paraoxonase/arylesterase (HUMPONA) gene is a risk factor for coronary artery disease. (1995)

Coronary artery disease (CAD) is a complex trait caused by a number of genetic and environmental factors. Recently, paraoxonase/arylesterase (PONA) enzyme has been implicated in the pathogenesis of atherosclerosis. There is a 10-40-fold variability in the activity of this enzyme among individuals. This variability is due to the presence of an A/G polymorphism in the coding region of the gene (HUMPONA). The A and G alleles code for glutamine (A genotype) and arginine (B genotype), respectively. Individuals with A genotype have a lower enzymatic activity than those with B genotype. We determined the HUMPONA genotypes and alleles in 223 patients with angiographically documented CAD and in 247 individuals in the general population. The distribution of genotypes were in Hardy-Weinberg equilibrium in patients and in controls. Genotypes A and B were present in 120 (49%) and 28 (11%) individuals in controls and in 68 (30%) and 40 (18%) patients with CAD, respectively (chi squared= 16.5, P= 0.0003). The frequency of the A allele was 0.69 in controls and 0.56 in patients (OR= 1.7, P= 0.0001). There were no differences in the distribution of HUMPONA genotypes in the subgroups of patients with restenosis, myocardial infarction, or any of the conventional risk factors for CAD as compared with corresponding subgroups. In summary, variants of the HUMPONA gene are involved in predisposition to coronary atherosclerosis.
Genetic Animal Models of Alcohol and Drug Abuse (1994)

Behavioral and pharmacological responses of selectively bred and inbred rodent lines have been analyzed to elucidate many features of drug sensitivity and the adverse effects of drugs, the underlying mechanisms of drug tolerance and dependence, and the motivational states underlying drug reward and aversion. Genetic mapping of quantitative trait loci (QTLs) has been used to identify provisional chromosomal locations of genes influencing such pharmacological responses. Recent advances in transgenic technology, representational difference analysis, and other molecular methods now make feasible the positional cloning of QTLs that influence sensitivity to drugs of abuse. This marks a new period of synthesis in pharmacogenetic research, in which networks of drug-related behaviors, their underlying pharmacological, physiological, and biochemical mechanisms, and particular genomic regions of interest are being identified.
Contribution of cytochrome P450 3A4 and 3A5 to the metabolism of atorvastatin (2008)

Atorvastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor that is mainly metabolized by cytochrome P450 (CYP) 3A4. A recent study showed that the lipid-lowering effect of statins is affected by the CYP3A5 polymorphism. Therefore, it was investigated whether CYP3A5 contributes to the metabolism of atorvastatin. Two metabolites of atorvastatin, para- and ortho-hydroxyatorvastatin, were produced by human liver microsomes and human recombinant CYP3A enzymes, and the enzyme kinetic pattern exhibited substrate inhibition. The intrinsic clearance (CL(int)) rates of para- and ortho-hydroxyatorvastatin by CYP3A4 were 2.4- and 5.0-fold of the respective CL(int) rates of CYP3A5, indicating that CYP3A4 is the major P450 isoform responsible for atorvastatin metabolism. These results suggest that atorvastatin is preferentially metabolized by CYP3A4 rather than by CYP3A5, and thus the genetic CYP3A5 polymorphism might not be an important factor in the inter-individual variation of atorvastatin disposition and pharmacodynamics in human.
Optimal Placement of Cameras in Floorplans to Satisfy Task Requirements and Cost Constraints (2004)

Abstract. In many multi-camera vision systems the effect of camera locations on the task-specific quality of service is ignored. Researchers in Computational Geometry have proposed elegant solutions for some sensor location problem classes. Unfortunately, these solutions utilize unrealistic assumptions about the cameras’ capabilities that make these algorithms unsuitable for many real-world computer vision applications. In this paper, the general camera placement problem is first defined with assumptions that are more consistent with the capabilities of realworld cameras. Given a floorplan to be observed, the problem is to efficiently compute a camera layout such that certain task-specific constraints are met and with minimal camera setup cost. A solution to this problem is obtained via binary optimization over a discrete problem space. In preliminary experiments the performance of the system is demonstrated with two different practical experiments on a real floorplan. 1
Proteomic Identification and Functional Validation of Activins and Bone Morphogenetic Protein 11 as Candidate Novel Muscle Mass Regulators (2008)

Myostatin is a secreted TGF-beta family member that controls skeletal muscle growth. Humans, cattle, and dogs carrying natural loss-of-function mutations in the myostatin gene and myostatin knockout mice exhibit significant increases in skeletal muscle mass. Treatment of adult mice with antimyostatin antibodies also resulted in significant muscle mass increases. However, myostatin-knockout mice that were treated with a soluble form of the activin type II receptor (ActRII) B increased their muscle mass by an additional 15-25%, indicating that there is at least one additional ligand, in addition to myostatin, that functions to limit muscle growth. Here, both soluble ActRII and -IIB fragment-crystallizable proteins were used to affinity purify their native ligands from human and mouse sera. Using mass spectrometry-based proteomics and in vitro binding assays we have identified and confirmed that a number of TGF-beta family members, including myostatin, activins-A, -B, and -AB, bone morphogenetic proteins (BMPs) -9, -10, and -11, bind to both ActRIIs. Many of these factors, such as BMPs-11, -9, and -10 were discovered in systemic circulation for the first time, indicating that these ligands may also act in an endocrine fashion. Using a promoter-specific gene reporter assay, we demonstrated that soluble ActRIIB fragment-crystallizable proteins can inhibit the canonical signaling induced by these ligands. In addition, like myostatin, these factors were able to block the differentiation of myoblast cells into myotubes. However, in addition to myostatin, only BMP-11, and activins-A, -B, and -AB could be blocked from inhibiting the myoblast-to-myotube differentiation with both soluble ActRIIs, thus implicating them as potential novel regulators of muscle growth.
The relapsing fever agent Borrelia hermsii has multiple copies of its chromosome and linear plasmids. (1992)

Borrelia hermsii, a spirochete which causes relapsing fever in humans and other mammals, eludes the immune response by antigenic variation of the "Vmp" proteins. This occurs by replacement of an expressed vmp gene with a copy of a silent vmp gene. Silent and expressed vmp genes are located on separate linear plasmids. To further characterize vmp recombination, copy numbers were determined for two linear plasmids and for the 1-megabase chromosome by comparing hybridization of probes to native DNA with hybridization to recombinant plasmids containing borrelial DNA. Plasmid copy numbers were also estimated by ethidium bromide fluorescence. Total cellular DNA content was determined by spectrophotometry. For borrelias grown in mice, copy numbers and 95% confidence intervals were 14 (12-17) for an expression plasmid, 8 (7-9) for a silent plasmid, and 16 (13-18) for the chromosome. Borrelias grown in broth medium had one-fourth to one-half this number of plasmids and chromosomes. Staining of cells with 4',6-diamidino-2-phenylindole revealed DNA to be distributed throughout most of the spirochete's length. These findings indicate that borrelias organize their total cellular DNA into several complete genomes and that cells undergoing serotype switches do one or more of the following: (1) coexpress Vmps from switched and unswitched expression plasmids for at least three to five generations, (2) suppress transcription from some expression plasmid copies, or (3) partition expression plasmids nonrandomly. The lower copy number of the silent plasmid indicates that nonreciprocal Vmp gene recombination may result from loss of recombinant silent plasmids by segregation.
FP312MACROPHAGE POLARIZATION AND GRANULOMA FORMATION IN HYPERURICEMIA-ASSOCIATED CHRONIC KIDNEY DISEASE (2018)

in HK2 cells. Targeting STMN1 with sh-RNA produced a similar effect as miR-493 overexpression. On contrast, the miR-493 inhibitor reversed these effects in vitro. Consistent with these results,miR-493 sponge adeno-associated virus (AAV) reduced the expression of profibrotic factors and increased STMN1 in vivo. CONCLUSIONS: These results suggested that the miR-493-STMN1 pathway contributes to hypoxia-inducedtubular epithelial cell G2/M arrest and renal fibrosis. Abrogating G2/M arrest and blocking miR-493-STMN1 pathway will provide novel insight for the future development of new anti-fibrosis therapy.
Primary SIVsm Isolates Use the CCR5 Coreceptor from Sooty Mangabeys Naturally Infected in West Africa: A Comparison of Coreceptor Usage of Primary SIVsm, HIV-2, and SIVmac (1998)

Genetically divergent strains of simian immunodeficiency virus (SIV) from macaques (mac), chimpanzees, and sooty mangabeys (SM) efficiently used rhesus and human CCR5 (R5), but not CXCR4 (xR4), for cell entry. Thus far, however, no studies have characterized primary SIVsm strains for their use of coreceptors derived from their own natural host. Coreceptor usage of two primary, blood-derived SIVsm isolates, SIVsmSL92b and SIVsmFNS from naturally infected sooty mangabeys, was determined. Primary SIVsm efficiently used SM-CCR5 expressed on HOS.CD4 and U87.CD4 cells. Sequence polymorphisms in CCR5 found in four sooty mangabeys did not alter viral entry. Unlike primary rhesus blood-derived R5-tropic SIVmac251, primary SM blood-derived R5-tropic SIVsm was strongly CD4 dependent. The SM-CXCR4 gene was fully functional for xR4-tropic primate lentiviruses, but was not used by primary SIVsm. Therefore, the lack of xR4 tropism among naturally occurring SIVsm strains was not due to CxCR4 gene defects in the natural host. SIVmac derived from four macaques with AIDS also did not use macaque- or SM-derived CXCR4, showing that xR4 tropism did not develop during progression to disease as for humans infected with HIV-1. Three of four primary HIV-2 strains used CCR5 from human, sooty mangabey, and macaque. The fourth, HIV-27924A, obtained from a patient with AIDS, was xR4-tropic. Because SIVmac is most closely related to HIV-2, SIVmac might be expected to rnimic tropisms of HIV-2 infections. However, the correlation between xR4 tropism and AIDS may be a species-specific phenomenon limited to humans. The R5-tropic primary SIVsm and HIV-2 strains grew in CCR5-negative human PBMC, consistent with their use of non-CCR5 coreceptors. However, primary SIVsmSL92b did not use non-CCR5 coreceptors efficiently. The two primary SIVsm isolates replicated poorly in CEMx174 cells, which do not express CCR5, compared to CCR5-positive PM1 cells. SIVmac grew equally well in both cell lines. The findings show that SM-chemokine receptors are fully functional for virus entry and that multicoreceptor tropism is a common property of primary lentiviruses within the SIVsm/HIV-2 subfamily.
[Dynamic monitoring of plasma circulating DNA in patients with acute myeloid leukemia and its clinical significance]. (2012)

This study was aimed to quantify plasma circulating DNA level in patients with acute myeloid leukemia (AML) and to evaluate its clinical significance. 66 AML patients and 100 controls (60 healthy subjects for health examination, 20 cases of benign hematopathy, and 20 cases of solid tumors) were enrolled in this study. Blood samples were collected from AML patients at different status of disease and control groups. Circulating DNA were drew by using the BILATEST DNA Kit. The level of plasma DNA was determined by using duplex real-time quantitative PCR. The results showed that the median value of plasma DNA level in AML patients at diagnosis was 168.5 (73.4 - 245.1) ng/ml, significantly higher than those in three control groups, and the median level in male patients was significantly higher than that in female patients (P = 0.019). No significant difference was found in plasma DNA level of the patients at different ages and with different FAB subtypes. Compared with level before chemotherapy, the plasma DNA levels in complete remission patients and partial remission patients decreased significantly, and with no statistical difference from level of healthy controls, but was significantly different from level of non-remission patients (P < 0.05). Following up of 31 remission patients showed that the plasma DNA level increased in 5 out of 6 (83.3%) relapsed patients, but no increase was found in 22 out of 25 (88.0%) non-relapsed patients. It is concluded that the quantification of plasma DNA may be useful for evaluating therapeutic effects and monitoring relapse in AML patients.
Current status of monoclonal antibodies for imaging and therapy of prostate cancer. (1994)

It is clear that there is significant need for improved staging and therapy of prostate cancer. The attributes and strengths of MoAbs seem particularly well-suited to the setting of prostate cancer. Recent progress in the application of MoAbs to in vivo imaging and therapy is encouraging. Clearly, further such efforts in prostate cancer are warranted.
Bio-inspired detoxification using 3D-printed hydrogel nanocomposites (2014)

Rationally designed nanoparticles that can bind toxins show great promise for detoxification. However, the conventional intravenous administration of nanoparticles for detoxification often leads to nanoparticle accumulation in the liver, posing a risk of secondary poisoning especially in liver-failure patients. Here we present a liver-inspired three-dimensional (3D) detoxification device. This device is created by 3D printing of designer hydrogels with functional polydiacetylene nanoparticles installed in the hydrogel matrix. The nanoparticles can attract, capture and sense toxins, while the 3D matrix with a modified liver lobule microstructure allows toxins to be trapped efficiently. Our results show that the toxin solution completely loses its virulence after treatment using this biomimetic detoxification device. This work provides a proof-of-concept of detoxification by a 3D-printed biomimetic nanocomposite construct in hydrogel, and could lead to the development of alternative detoxification platforms.
B7-H3: another molecule marker for Mo-DCs? (2005)

Using a newly generated monoclonal antibody (2E6) against human B7-H3, we explored the expression of the molecule on dendritic cells derived from monocytes (Mo-DCs). Its expression was examined by means of immunostaining and flow cytometric (FCM) analysis. The results showed that B7-H3 was expressed in the course of Mo-DC maturation induced with interleukin 4 (IL-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF). The expression could be detected at all the stages of Mo-DC differentiation, and remained at a quite stable level. Interestingly, B7-H3 was not expressed by T cells and B cells, even these cells were activated respectively by PHA or PWM. A weak expression could be detected on resting monocytes. These data showed that constitutive expression of B7-H3 at a high level was found on imDCs and mDCs derived from monocytes. Due to no expression on T cells and B cells, we speculate that B7-H3 might be another valuable molecule marker for Mo-DCs.