gebhart/patrepeval huggingface dataset:
Amniotic epithelial cells transform into neuron-like cells in the ischemic brain (2001)

We investigated the potential use of rat amniotic epithelial (RAE) cells as donor cells for transplantation-based therapy in brain ischemia. In vitro, RAE cells were positive for both neuronal and neural stem cell markers, neurofilament microtubule-associated protein 2 and nestin. RT-PCR revealed that these cells express nestin mRNA. The RAE cells were transplanted into the hippocampus of adult gerbils that were subjected to temporal occlusion of bilateral carotid arteries. Five weeks after transplantation, grafted cells migrated into the CA1 pyramidal layer that showed selective neuronal death, and survived in a manner similar to CA1 pyramidal neurons. These results suggest that intracerebral transplantation of amniotic epithelial cells may have therapeutic potential for the treatment of ischemic damage in neuronal disorders.
Mismatch Repair by Efficient Nick-Directed, and Less Efficient Mismatch-Specific, Mechanisms in Homologous Recombination Intermediates in Chinese Hamster Ovary Cells (1997)

Repair of single-base mismatches formed in recombination intermediates in vivo was investigated in Chinese hamster ovary cells. Extrachromosomal recombination was stimulated by double-strand breaks (DSBs) introduced into regions of shared homology in pairs of plasmid substrates heteroallelic at 11 phenotypically silent mutations. Recombination was expected to occur primarily by single-strand annealing, yielding predicted heteroduplex DNA (hDNA) regions with three to nine mismatches. Product spectra were consistent with hDNA only occurring between DSBs. Nicks were predicted on opposite strands flanking hDNA at positions corresponding to original DSB sites. Most products had continuous marker patterns, and observed conversion gradients closely matched predicted gradients for repair initiated at nicks, consistent with an efficient nick-directed, excision-based mismatch repair system. Discontinuous patterns, seen in approximately 10% of products, and deviations from predicted gradients provided evidence for less efficient mismatch-specific repair, including G-A-->G-C specific repair that may reflect processing by a homologue of Escherichia coli MutY. Mismatch repair was > 80% efficient, which is higher than seen previously with covalently closed, artificial hDNA substrates. Products were found in which all mismatches were repaired in a single tract initiated from one or the other nick. We also observed products resulting from two tracts of intermediate length initiated from two nicks.
Role of IL-17 and regulatory T lymphocytes in a systemic autoimmune disease (2006)

To explore the interactions between regulatory T cells and pathogenic effector cytokines, we have developed a model of a T cell-mediated systemic autoimmune disorder resembling graft-versus-host disease. The cytokine responsible for tissue inflammation in this disorder is interleukin (IL)-17, whereas interferon (IFN)-gamma produced by Th1 cells has a protective effect in this setting. Because of the interest in potential therapeutic approaches utilizing transfer of regulatory T cells and inhibition of the IL-2 pathway, we have explored the roles of these in the systemic disease. We demonstrate that the production of IL-17 and tissue infiltration by IL-17-producing cells occur and are even enhanced in the absence of IL-2. Regulatory T cells favor IL-17 production but prevent the disease when administered early in the course by suppressing expansion of T cells. Thus, the pathogenic or protective effects of cytokines and the therapeutic capacity of regulatory T cells are crucially dependent on the timing and the nature of the disease.
Murine and Human Autotaxin α, β, and γ Isoforms (2008)

Autotaxin is a type II ectonucleotide pyrophosphate phosphodiesterase enzyme. It has been recently discovered that it also has a lysophospholipase D activity. This enzyme probably provides most of the extracellular lysophosphatidic acid from lysophosphatidylcholine. The cloning and tissue distribution of the three isoforms (imaginatively called alpha, beta, and gamma) from human and mouse are reported in this study, as well as their tissue distribution by PCR in the human and mouse. The fate of the alpha isoform from human was also studied after purification and using mass spectrometry. Indeed, this particular isoform expresses the intron 12 in which a cleavage site is present, leading to a rapid catabolism of the isoform. For the human isoform gamma and the total autotaxin mRNA expression, quantitative PCR is presented in 21 tissues. The isoforms were expressed in two different hosts, insect cells and Chinese hamster ovary cells, and were highly purified. The characteristics of the six purified isoforms (pH and temperature dependence, K(m) and V(max) values, and their dependence on metal ions) are presented in this study. Their sensitivity to a small molecule inhibitor, hypericin, is also shown. Finally, the specificity of the isoforms toward a large family of lysophosphatidylcholines is reported. This study is the first complete description of the reported autotaxin isoforms.
Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells. (1994)

Approximately 30% of human breast and ovarian cancers have amplification and/or overexpression of HER-2/neu gene which encodes a cell surface growth-factor receptor. Overexpression of this receptor, p185HER-2/neu, is associated with poor outcome and may predict clinical response to chemotherapy. Antibodies to HER-2/neu receptor have a cytostatic effect in suppressing growth of cells with overexpression of p185HER-2/neu. To elicit a cytocidal effect, therapy with antireceptor antibody was used in combination with the DNA-damaging drug, cisplatin, and this combined treatment produced a synergistic decrease in cell growth. In addition, antibody mediated an increased sensitivity to cisplatin in drug-resistant ovarian carcinoma cells containing multiple copies of HER-2/neu gene. To evaluate the mechanism for this synergy, unscheduled DNA synthesis was measured in cancer cells using incorporation of [3H]thymidine and autoradiography, and formation and repair of cisplatin-induced DNA adducts was also measured. Treatment with cisplatin led to a marked, dose-dependent increase in unscheduled DNA synthesis which was significantly reduced by combined treatment with antireceptor antibody in HER-2/neu-overexpressing cells. Therapy with antibody to HER-2/neu receptor also led to a 35-40% reduction in repair of cisplatin-DNA adducts after cisplatin exposure and, as a result, promoted drug-induced killing in target cells. This phenomenon which we term receptor-enhanced chemosensitivity may provide a rationale for more selective targeting and exploitation of overexpressed growth factor receptors in cancer cells, thus leading to new strategies for clinical intervention.
Mechanistic study of microbial control of hydrogen sulfide production in oil reservoirs (2001)

Microbial control of biogenic production of hydrogen sulfide in oil fields was studied in a model system consisting of pure cultures of the nitrate-reducing, sulfide-oxidizing bacterium (NR-SOB) Thiomicrospira sp. strain CVO and the sulfate-reducing bacterium (SRB) Desulfovibrio sp. strain Lac6, as well as in microbial cultures enriched from produced water of a Canadian oil reservoir. The presence of nitrate at concentrations up to 20 mM had little effect on the rate of sulfate reduction by a pure culture of Lac6. Addition of CVO imposed a strong inhibition effect on production of sulfide. In the absence of added nitrate SRB we were able to overcome this effect after an extended lag phase. Simultaneous addition of CVO and nitrate stopped the production of H2S immediately. The concentration of sulfide decreased to a negligible level due to nitrate-dependent sulfide oxidation activity of CVO. This was not prevented by raising the concentration of Na-lactate, the electron donor for sulfate reduction. Similar results were obtained with enrichment cultures. Enrichments of produced water with sulfide and nitrate were dominated by CVO, whereas enrichments with sulfate and Na-lactate were dominated by SRB. Addition of an NR-SOB enrichment to an SRB enrichment inhibited the production of sulfide. Subsequent addition of sufficient nitrate caused the sulfide concentration to drop to zero. A similar response was seen in the presence of nitrate alone, although after a pronounced lag time, it was needed for emergence of a sizable CVO population. The results of the present study show that two mechanisms are involved in microbial control of biogenic sulfide production. First, addition of NR-SOB imposes an inhibition effect, possibly by increasing the environmental redox potential to levels which are inhibitory for SRB. Second, in the presence of sufficient nitrate, NR-SOB oxidize sulfide, leading to its complete removal from the environment. Successful microbial control of H2S in an oil reservoir is crucially dependent on the simultaneous presence of NR-SOB (either indigenous population or injected) and nitrate in the environment.
β-III-spectrin spinocerebellar ataxia type 5 mutation reveals a dominant cytoskeletal mechanism that underlies dendritic arborization (2017)

A spinocerebellar ataxia type 5 (SCA5) L253P mutation in the actin-binding domain (ABD) of β-III-spectrin causes high-affinity actin binding and decreased thermal stability in vitro. Here we show in mammalian cells, at physiological temperature, that the mutant ABD retains high-affinity actin binding. Significantly, we provide evidence that the mutation alters the mobility and recruitment of β-III-spectrin in mammalian cells, pointing to a potential disease mechanism. To explore this mechanism, we developed a <i>Drosophila</i> SCA5 model in which an equivalent mutant <i>Drosophila</i> β-spectrin is expressed in neurons that extend complex dendritic arbors, such as Purkinje cells, targeted in SCA5 pathogenesis. The mutation causes a proximal shift in arborization coincident with decreased β-spectrin localization in distal dendrites. We show that SCA5 β-spectrin dominantly mislocalizes α-spectrin and ankyrin-2, components of the endogenous spectrin cytoskeleton. Our data suggest that high-affinity actin binding by SCA5 β-spectrin interferes with spectrin-actin cytoskeleton dynamics, leading to a loss of a cytoskeletal mechanism in distal dendrites required for dendrite stabilization and arbor outgrowth.
Design of peptides that bind in the minor groove of DNA at 5'-(A,T)G(A,T)C(A,T)-3' sequences by a dimeric side-by-side motif (1992)

The designed peptides pyridine-2-carboxamide-netropsin (2-PyN) and 1-methylimidazole-2-carboxamide-netropsin (2-ImN) are crescent-shaped synthetic analogs of the natural products netropsin (N) and distamycin A (D). Footprinting experiments indicate that the peptides 2-PyN and 2-ImN bind specifically the 5 base pair sequence 5'-TGTCA-3'. Affinity cleaving data suggest that the complexes, 2-ImN.5'-TGTCA-3' and 2-PyN.5'-TGTCA-3', are composed of two equivalent orientations which disfavor a 1:1 model. The footprinting and affinity cleaving data are in accord with a 2:1 complex where a novel side-by-side antiparallel dimer binds in the minor groove of double-helical DNA.
Latent Autoimmune Diabetes in Adults (2005)

Latent autoimmune diabetes in adults (LADA) is a disorder in which, despite the presence of islet antibodies at diagnosis of diabetes, the progression of autoimmune beta-cell failure is slow. LADA patients are therefore not insulin requiring, at least during the first 6 months after diagnosis of diabetes. Among patients with phenotypic type 2 diabetes, LADA occurs in 10% of individuals older than 35 years and in 25% below that age. Prospective studies of beta-cell function show that LADA patients with multiple islet antibodies develop beta-cell failure within 5 years, whereas those with only GAD antibodies (GADAs) or only islet cell antibodies (ICAs) mostly develop beta-cell failure after 5 years. Even though it may take up to 12 years until beta-cell failure occurs in some patients, impairments in the beta-cell response to intravenous glucose and glucagon can be detected at diagnosis of diabetes. Consequently, LADA is not a latent disease; therefore, autoimmune diabetes in adults with slowly progressive beta-cell failure might be a more adequate concept. In agreement with proved impaired beta-cell function at diagnosis of diabetes, insulin is the treatment of choice.
Efficacy of antiaggregants for the pine engraver, Ipspini (Coleoptera: Scolytidae) (1994)

The responses of pine engravers, Ipspini (Say), in British Columbia to ipsdienol-baited traps containing low, medium, and high dose rates of the antiaggregants verbenone and ipsenol, released from impregnated polyethylene and polypropylene beads, respectively, remained significantly lower than responses to ipsdienol-baited control traps throughout the spring. During the summer, the responses remained low only in traps containing medium and high dose rates of impregnated beads. Antiaggregant treatment densities of 100 and 400 bubble cap release points per hectare reduced the numbers of pine engravers caught in ipsdienol-baited, multiple-funnel traps by 66.1 and 76.8%, respectively. In 50 × 50 m thinning-simulation plots treated with a broadcast distribution of antiaggregant-impregnated beads in 1990, 32.9% of the felled lodgepole pines, Pinuscontorta Dougl., were attacked; in untreated control plots, 53.1% were attacked. The mean attack density per square metre of available bark surface in the treated plots (1.3) was significantly lower than that in the untreated plots (1.9); however, where attack occurred there was no difference (8.8 and 9.4 attacks/m 2 , respectively). In a 1991 experiment, verbenone- and ipsenol-impregnated beads were applied to 15 × 15 m thinning-simulation plots at initial release rates of 2.5 mg of verbenone and 0.05 mg of ipsenol per square metre of ground surface per day, and at double these rates. For three treatments, low and high rates 3 weeks prior to the first attack by I. pini and a high rate 2 weeks prior to attack, the mean attacks per square metre of available bark surface per week were reduced by 77.1, 82.9, and 97.1%, respectively, compared with attacks on felled pines in untreated control plots. The results of these experiments suggest that a timely application of broadcast antiaggregants would prevent the development of an outbreak population of I. pini.
Chemosensitization of Human Renal Cell Cancer Using Antisense Oligonucleotides Targeting the Antiapoptotic Gene Clusterin (2001)

These findings confirm that the use of clusterin ASO may be a feasible strategy to enhance chemosensitivity for patients with advanced RCC.
Family Reunion Services: An Examination of a Process Used to Successfully Reunite Families (1998)

Family Reunion Services, an intensive-home-based service for families whose children are unlikely to return home without additional services, was evaluated. The 196 children who received FRS services and remained home had fewer previous placements, were more likely to be black and to come from families where the FRS worker intervened in the areas of parenting skills or communication. FRS workers' activities are described.
Characterization of a K+-Induced Conformational Switch in a Human Telomeric DNA Oligonucleotide Using 2-Aminopurine Fluorescence (2009)

Human telomeric DNA consists of tandem repeats of the DNA sequence d(GGGTTA). Oligodeoxynucleotide telomere models such as d[A(GGGTTA)(3)GGG] (Tel22) fold in a cation-dependent manner into quadruplex structures consisting of stacked G-quartets linked by d(TTA) loops. NMR has shown that in Na(+) solutions Tel22 forms a "basket" topology of four antiparallel strands; in contrast, Tel22 in K(+) solutions consists of a mixture of unknown topologies. Our previous studies on the mechanism of folding of Tel22 and similar telomere analogues utilized changes in UV absorption between 270 and 325 nm that report primarily on G-quartet formation and stacking showed that quadruplex formation occurs within milliseconds upon mixing with an appropriate cation. In this study, we assess the dynamics and equilibria of folding of specific loops by using Tel22 derivatives in which the dA residues were serially substituted with the fluorescent reporter base, 2-aminopurine (2-AP). Tel22 folding induced by Na(+) or K(+) assessed by changes in 2-AP fluorescence consists of at least three kinetic steps with time constants spanning a range from milliseconds to several hundred seconds. Na(+)-dependent equilibrium titrations of Tel22 folding could be approximated as a cooperative two-state process. In contrast, K(+)-dependent folding curves were biphasic, revealing that different conformational ensembles are present in 1 and 30 mM K(+). This conclusion was confirmed by (1)H NMR. Molecular dynamics simulations revealed a K(+) binding pocket in Tel22 located near dA1 that is specific for the so-called hybrid-1 conformation in which strand 1 is in a parallel arrangement. The possible presence of this topologically specific binding site suggests that K(+) may play an allosteric role in regulating telomere conformation and function by modulating quadruplex tertiary structure.
Endometriosis: Interaction of Immune and Endocrine Systems (2003)

Endometriosis is a common gynecologic disorder characterized by the presence of endometrial tissue outside the uterine cavity. Although no single theory can explain all cases of endometriosis, the most commonly accepted theory is Sampson's theory of retrograde menstruation. Retrograde menstruation occurs in 76 to 90% of women. The much lower prevalence of endometriosis suggests that additional factors determine susceptibility to endometriosis. Endometriosis is associated with changes in both cell-mediated and humoral immunity. Impaired natural killer cell activity resulting in inadequate removal of refluxed menstrual debris may play a role in the development of endometriotic implants. Moreover, although the peritoneal fluid of women with endometriosis contains increased numbers of immune cells, these seem to facilitate rather than inhibit the development of endometriosis. Macrophages that would be expected to clear endometrial cells from the peritoneal cavity appear to enhance their proliferation by secreting growth factors and cytokines. Although it is unclear whether these immunologic alterations induce endometriosis or are a consequence of its presence, they appear to play an important role in allowing endometriosis implants to persist and progress and contribute to the development of associated infertility and pelvic pain. Danazol and gonadotropin-releasing hormone (GnRH) agonists are commonly used for the medical treatment of endometriosis. These medications seem to down-regulate cellular and humoral immune responses concomitant with their effect on endometriotic implants. Immunomodulatory effects of danazol and GnRH agonists are likely to contribute to the observed clinical improvement associated with their use.
Profiling of genes expressed in peripheral blood mononuclear cells predicts glucocorticoid sensitivity in asthma patients (2005)

Gene expression profiles were examined in freshly isolated peripheral blood mononuclear cells (PBMC) from two independent cohorts (training and test sets) of glucocorticoid (GC)-sensitive (n = 64) and GC-resistant (n = 42) asthma patients in search of genes that accurately predict responders and nonresponders to inhaled corticosteroids. A total of 11,812 genes were examined with high-density oligonucleotide microarrays in both resting PBMC (106 patients) and cells treated in vitro with IL-1beta and TNF-alpha combined (88 patients), with or without GC. A total of 5,011 genes were expressed at significant levels in the PBMC, and 1,334 of those were notably up-regulated or down-regulated by IL-1beta/TNF-alpha treatment. The expression changes of 923 genes were significantly reversed in GC responders in the presence of GC. The expression pattern of 15 of these 923 genes that most accurately separated GC responders (n = 26) from the nonresponders (n = 18) in the training set, based on the weighted voting algorithm, predicted the independent test set of equal size with 84% accuracy. The expression accuracy of these genes was confirmed by real-time-quantitative PCR, wherein 11 of the 15 genes predicted GC sensitivity at baseline with 84% accuracy, with one gene predicting at 81% in an independent cohort of 79 patients. We conclude that we have uncovered gene expression profiles in PBMC that predict clinical response to inhaled GC therapy with meaningful accuracy. Upon validation in an independent study, these results support the development of a diagnostic test to guide GC therapy in asthma patients.
ATP is the predominant sympathetic neurotransmitter in rat mesenteric arteries at high pressure (2007)

Most studies of neurovascular transmission in isolated small mesenteric arteries have used either isometric recording techniques or measured vasoconstriction in vessels with no distending pressure. Here we have used pressure myography to assess the contribution of noradrenaline and ATP to sympathetic neurotransmission in rat second-order mesenteric arteries. In arteries pressurized to 30 or 90 mmHg, activation of sympathetic axons with trains of electrical stimuli (50 pulses, 0.5-10 Hz) evoked frequency-dependent vasoconstrictions that increased in amplitude at higher pressure. In the presence of the P2-receptor antagonist suramin (0.1 mM), the amplitude of vasoconstrictions to trains at 2 and 10 Hz did not differ at 30 and 90 mmHg. In contrast, in the presence of the alpha(1)-adrenoceptor antagonist prazosin (0.1 microm) vasoconstrictions at 90 mmHg were larger than those at 30 mmHg. At both pressures, the combination of prazosin and suramin virtually abolished constrictions. The purinergic component of vasoconstriction (prazosin-resistant) was almost abolished by the L-type Ca(2+) channel antagonist nifedipine (1 microm). Increasing pressure from 30 to 90 mmHg decreased the resting membrane potential and increased the amplitude of purinergic excitatory junction potentials. These findings indicate that the contribution of ATP to neurovascular transmission increases when the pressure is raised from 30 to 90 mmHg, which is similar to the pressure second-order mesenteric arteries experience in vivo, and that Ca(2+) influx through L-type Ca(2+) channels is largely responsible for purinergic activation of the vascular smooth muscle.
Kagome hollow-core photonic crystal fiber probe for Raman spectroscopy (2012)

We demonstrate the use of a large-pitch Kagome-lattice hollow-core photonic crystal fiber probe for Raman spectroscopy. The large transmission bandwidth of the fiber enables both the excitation and Raman beams to be transmitted through the same fiber. As the excitation beam is mainly transmitted through air inside the hollow core, the silica luminescence background is reduced by over 2 orders of magnitude as compared to standard silica fiber probes, removing the need for fiber background subtraction.
Iron-Catalyzed [2π + 2π] Cycloaddition of α,ω-Dienes:  The Importance of Redox-Active Supporting Ligands (2006)

The bis(imino)pyridine iron bis(dinitrogen) complex, (iPrPDI)Fe(N2)2 (iPrPDI = 2,6-(2,6-iPr2C6H3NCR)2C5H3N), serves as an efficient precursor for the catalytic [2pi + 2pi] cycloaddition of alpha,omega-dienes to yield the corresponding bicycles. For amine substrates, the rate of catalytic turnover increases with the size of the nitrogen substituents, demonstrating competing heterocycle coordination and product inhibition. In one case, a bis(imino)pyridine iron azobicycloheptane product was characterized by X-ray diffraction. Preliminary mechanistic studies highlight the importance of the redox activity of the bis(imino)pyridine ligand to maintain the ferrous oxidation state throughout the catalytic cycle.