gebhart/patrepeval huggingface dataset:
Purification of Gastroprotective Triterpenoids from the Stem Bark ofAmphipterygium adstringens; Role of Prostaglandins, Sulfhydryls, Nitric Oxide and Capsaicin-Sensitive Neurons (2003)

In this investigation three bioactive compounds, responsible for the gastroprotective property of Amphipterygium adstringens, were purified from an active dichloromethane fraction. These compounds were 3alpha-hydroxymasticadienonic acid, beta-sitosterol and 3- epi-oleanolic acid. The latter was the most active compound (88.8 % of gastroprotection) followed by 3alpha-hydroxymasticadienoic acid and beta-sitosterol (69.8 and 42.5 % of gastroprotection, respectively). Carbenoxolone was used as positive control and it showed 88.4 % of gastroprotection. Masticadienonic acid was also isolated from the active fraction, but it was unable to inhibit the ethanol-induced gastric lesions. The gastroprotection of the methanol extract was completely inhibited by the pretreatment with l-NAME and attenuated by pretreatment with indomethacin and N-ethylmaleimide. These results suggest that endogenous nitric oxide plays an important role in the gastroprotection of A. adstringens methanol extract on ethanol-induced gastric mucosal lesions and that there is partial participation by prostaglandins and endogenous sulfhydryls. The effect of 3alpha-hydroxymasticadienonic acid was attenuated only by pretreatment with N-ethylmaleimide, indicating that endogenous sulfhydryls (thiols) participate in its gastroprotective mechanism. Capsaicin-sensitive afferent neurons do not participate in the gastroprotection of either the methanol extract or 3alpha-hydroxymasticadienoic acid.
Epidemic transmission of enterically transmitted non-A, non-B hepatitis in Mexico, 1986-1987 (1990)

Outbreaks of acute hepatitis occurred in Huitzililla and Telixtac, two rural villages 70 miles south of Mexico City, Mexico, in late 1986. The first outbreak began in Huitzililla in June of that year, 1 month after the start of the rainy season. A census revealed 94 icteric case subjects, for an attack rate of 5%; two women died. Attack rates were higher for persons older than 15 years (10%) than for younger persons. A case-control study showed that illness was highly associated with water-related factors. The second outbreak began in August 1986 in Telixtac. There were 129 case subjects, for an attack rate of 6%; one woman died. Epidemiologic findings were similar to those in Huitzililla, except that most disease transmission was not linked to unsafe water sources. None of 62 case subjects in Huitzililla and only 2 of 53 case subjects in Telixtac tested had serological evidence for recent infection with hepatitis A or B. Two of eight stool samples from Huitzililla and one of eight stool samples from Telixtac were positive by immune electron microscopy for 32- to 34-nm viruslike particles similar to those seen in cases of enterically transmitted non-A, non-B hepatitis from Asia. To our knowledge, these investigations document for the first time the epidemic transmission of enterically transmitted non-A, non-B hepatitis virus in the Americas. (<i>JAMA</i>. 1990;263:3281-3285)
Using SIFT and PolyPhen to Predict Loss-of-Function and Gain-of-Function Mutations (2010)

Although SIFT and PolyPhen may be useful in prioritizing changes that are likely to cause a loss of protein function, their low specificity means that their predictions should be interpreted with caution and further evidence to support/refute pathogenicity should be sought before reporting novel missense changes.
Topical cyclodextrin reduces amyloid beta and inflammation improving retinal function in ageing mice (2015)

Retinal ageing results in chronic inflammation, extracellular deposition, including that of amyloid beta (Aβ) and declining visual function. In humans this can progress into age-related macular degeneration (AMD), which is without cure. Therapeutic approaches have focused on systemic immunotherapies without clinical resolution. Here, we show using aged mice that 2-Hydroxypropyl-β-cyclodextrin, a sugar molecule given as eye drops over 3 months results in significant reductions in Aβ by 65% and inflammation by 75% in the aged mouse retina. It also elevates retinal pigment epithelium specific protein 65 (RPE65), a key molecule in the visual cycle, in aged retina. These changes are accompanied by a significant improvement in retinal function measured physiologically. 2-Hydroxypropyl-β-cyclodextrin is as effective in reducing Aβ and inflammation in the complement factor H knockout (Cfh(-/-)) mouse that shows advanced ageing and has been proposed as an AMD model. β-cyclodextrin is economic, safe and may provide an efficient route to reducing the impact of retinal ageing.
Synthesis and crystal structure of a novel tripyrrane-containing porphyrinogen-like macrocycle (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and crystal structure of a novel tripyrrane-containing porphyrinogen-like macrocycleJonathan L. Sessler, Martin R. Johnson, and Vincent LynchCite this: J. Org. Chem. 1987, 52, 19, 4394–4397Publication Date (Print):September 1, 1987Publication History Published online1 May 2002Published inissue 1 September 1987https://doi.org/10.1021/jo00228a048RIGHTS & PERMISSIONSArticle Views1149Altmetric-Citations144LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (2 MB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
A Cytokine-based model for the pathophysiology of Long COVID symptoms (2020)

The Long COVID group includes patients with mild-to-moderate symptoms, in whom recovery is prolonged, lasting months. Here we propose a model for the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production.In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with "brain fog," arthralgias, paresthesias, and GI and ophthalmic problems can all be attributed to elevated peripheral and central cytokines.There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A post-infectious ME/CFS model involving a dysfunctional peripheral and central cytokine inflammatory response and autoimmunity is emerging. DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS.
Characterization of a cell surface-expressed disulfide-linked dimer involved in murine T cell activation. (1988)

We have produced a hamster mAb, H1.2F3, which was derived by immunization with a murine TCR-gamma delta + epidermal T cell line. H1.2F3 immunoprecipitates a cell surface-expressed disulfide-linked dimer that has a m.w. of 85,000 under non-reducing conditions and consists of subunits of 35,000 to 39,000 m.w. This dimer is distinct from the CD3-associated TCR-gamma delta complex (CD3/TCR), inasmuch as H1.2F3 does not co-precipitate or co-modulate with the CD3/TCR complex and recognizes an Ag with a single-peptide backbone of 22,000 m.w. after N-Glycanase treatment. H1.2F3 is weakly reactive with a small percentage of cells from unfractionated thymus, spleen, or lymph node, but reactivity with both T and B lymphocytes is markedly enhanced by a brief period of stimulation with Con A or PMA in vitro. This enhancement requires de novo protein synthesis. Enhanced expression of the H1.2F3 Ag can also be induced in vivo by injection of Con A or anti-CD3. H1.2F3 is a potent stimulator of T, but not B, cell proliferation in the presence of PMA and FcR-bearing accessory cells. These functional and biochemical studies strongly suggest that the Ag recognized by H1.2F3 is the murine homologue of the human CD28 Ag recognized by mAb 9.3.
Cytoprotection &ldquo;gone astray&rsquo;&rsquo;: Nrf2 and its role in cancer (2014)

Nrf2 has gained great attention with respect to its pivotal role in cell and tissue protection. Primarily defending cells against metabolic, xenobiotic and oxidative stress, Nrf2 is essential for maintaining tissue integrity. Owing to these functions, Nrf2 is regarded as a promising drug target in the chemoprevention of diseases, including cancer. However, much evidence has accumulated that the beneficial role of Nrf2 in cancer prevention essentially depends on the tight control of its activity. In fact, the deregulation of Nrf2 is a critical determinant in oncogenesis and found in many types of cancer. Therefore, amplified Nrf2 activity has profound effects on the phenotype of tumor cells, including radio/chemoresistance, apoptosis protection, invasiveness, antisenescence, autophagy deficiency, and angiogenicity. The deregulation of Nrf2 can result from various epigenetic and genetic alterations directly affecting Nrf2 control or from the complex interplay of Nrf2 with numerous oncogenic signaling pathways. Additionally, alterations of the cellular environment, eg, during inflammation, contribute to Nrf2 deregulation and its persistent activation. Therefore, the status of Nrf2 as anti- or protumorigenic is defined by many different modalities. A better understanding of these modalities is essential for the safe use of Nrf2 as an activation target for chemoprevention on the one hand and as an inhibition target in cancer therapy on the other. The present review mainly addresses the conditions that promote the oncogenic function of Nrf2 and the resulting consequences providing the rationale for using Nrf2 as a target structure in cancer therapy.
Potential Role of the Amelogenin N-Terminus in the Regulation of Calcium Phosphate Formation in vitro (2011)

N-terminal and C-terminal (CT) domains of amelogenin have been shown to be essential for proper enamel formation. Recent studies have also suggested that although the C-terminus plays an apparent role in protein-mineral interactions, other amelogenin structural domains are involved. The objective was to explore the role of the amelogenin N-terminus in the regulation of calcium phosphate formation in vitro. Spontaneous mineralization studies were carried out using the phosphorylated (+P) and nonphosphorylated (-P) N-terminus of the leucine-rich amelogenin peptide (LRAP) that lacks the hydrophilic CT domain. Mineralization progress was monitored via changes in solution pH. Mineral phases formed were characterized using TEM, selected area electron diffraction, and FT-IR. In controls, amorphous calcium phosphate was initially formed and subsequently transformed to randomly oriented hydroxyapatite (HA) plate-like crystals. In contrast to the control, LRAP(+P)-CT stabilized ACP formation for >1 day, while LRAP(-P)-CT accelerated the transformation of ACP to HA but had little effect on crystal shape or orientation. In conclusion, the N-terminal domain found in LRAP, as in amelogenins, appears to have the capacity to interact with forming calcium phosphate mineral phases. Results suggest that the N-terminal domain of amelogenin may play a direct role in early stages of enamel formation.
Immunotherapeutic Advancements for Glioblastoma (2015)

Immunotherapy seeks to improve the body's immune response to a tumor. Currently, the principal mechanisms employed are: (1) to improve an aspect of the immune response (e.g., T cell activation) and (2) to encourage the targeting of particular antigens. The latter is typically achieved by exposing the immune system to the antigen in question, in vivo, or in vitro followed by re-introduction of the primed cells to the body. The clinical relevance of these approaches has already been demonstrated for solid tumors such as melanoma and prostate cancer. The central nervous system was previously thought to be immune privileged. However, we know now that the immune system is highly active in the brain and interacts with brain tumors. Thus, harnessing and exploiting this interaction represents an important approach for treating malignant brain tumors. We present a summary of progress in this area, focusing particularly on immune-checkpoint inhibition, vaccines, and T cell engineering.
Mechanisms of ventilator-induced lung injury (1993)

Ventilation with high tidal volumes can increase vascular filtration pressures; produce stress fractures of capillary endothelium, epithelium, and basement membrane; and cause lung rupture. Mechanical damage leads to leakage of fluid, protein, and blood into tissue and air spaces or leakage of air into tissue spaces. This process is followed by an inflammatory response and possibly a reduced defense against infection. Predisposing factors for lung injury are high peak inspiratory volumes and pressures, a high mean airway pressure, structural immaturity of lung and chest wall, surfactant insufficiency or inactivation, and preexisting lung disease. Damage can be minimized by preventing overdistention of functional lung units during therapeutic ventilation.
MIXED CHIMERISM OF CARDIOMYOCYTES AND VESSELS AFTER ALLOGENEIC BONE MARROW AND STEM-CELL TRANSPLANTATION IN COMPARISON WITH CARDIAC ALLOGRAFTS (2004)

Controversy persists about mixed chimerism (mCh) occurring in the hearts of patients after orthotopic cardiac transplantation in comparison with allogeneic bone marrow (BM) and peripheral blood stem-cell (PBSC) transplants. Cadaver hearts were examined after sex-mismatched transplantation by immunophenotyping combined with dual color fluorescence in situ hybridization (X and Y chromosome-specific probes). A striking disparity in the extent of mCh depending on the different transplantation procedures was recognizable. After allografting with PBSCs, 1.7% chimeric cardiomyocytes were detectable contrasting 5.4% of donor cells after full BM transplantation. In cardiac transplants, host-type endothelial cells (16.2%) and myocytes (14.3%) of the vessel walls were more often encountered than after BM and PBSC allografting. A sprouting of vascular structures into the donor heart after orthotopic cardiac transplantation has to be assumed, as does a pivotal role of the mesenchymal stem cells of the BM in the development of mCh.
Nuclear deformation characterizes Werner syndrome cells (2005)

Mutations in the lamin A gene have been shown, among other defects, to give rise to Hutchinson-Gilford progeria syndrome (HGPS) and to atypical Werner syndrome (WS), both of which are progeroid disorders. Here, we have investigated well-characterized WS patient cell strains that are compound heterozygous for mutations in the WRN gene. As in HGPS and in atypical WS, we found nuclear deformations to be characteristic of all cell strains studied. In WS cells centrosome number, assembly of the nuclear lamina and nuclear pore distribution occurred normally. Furthermore, nuclear deformations were not associated with a defect in lamin A expression. We propose that nuclear deformation is a universal characteristic of progeroid cells and may result from slow cell cycle progression.
T‐helper 17 cytokines (interleukins 17, 21, 22, and 6, and tumor necrosis factor‐α) in patients with alopecia areata: association with clinical type and severity (2015)

Our results showed high serum levels of Th17 cytokines among patients with AA that may suggest a functional role of these cytokines in the pathogenesis of this important skin disease. It could also provide the rationale for new treatment strategies in AA.
CSCW'92 demonstrations (1992)

Article CSCW'92 demonstrations Share on Authors: Michael J. Muller Bellcore, Room RRC-1H229, 444 Hoes Lane Piscataway, NJ Bellcore, Room RRC-1H229, 444 Hoes Lane Piscataway, NJView Profile , Aita Salasoo Bellcore, Room RRC-1H229, 444 Hoes Lane Piscataway, NJ Bellcore, Room RRC-1H229, 444 Hoes Lane Piscataway, NJView Profile Authors Info & Claims CSCW '92: Proceedings of the 1992 ACM conference on Computer-supported cooperative workDecember 1992 Pages 11–14https://doi.org/10.1145/143457.371592Published:01 December 1992 1citation318DownloadsMetricsTotal Citations1Total Downloads318Last 12 Months0Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Engineering cytosolic acetyl-coenzyme A supply in Saccharomyces cerevisiae: Pathway stoichiometry, free-energy conservation and redox-cofactor balancing (2016)

Saccharomyces cerevisiae is an important industrial cell factory and an attractive experimental model for evaluating novel metabolic engineering strategies. Many current and potential products of this yeast require acetyl coenzyme A (acetyl-CoA) as a precursor and pathways towards these products are generally expressed in its cytosol. The native S. cerevisiae pathway for production of cytosolic acetyl-CoA consumes 2 ATP equivalents in the acetyl-CoA synthetase reaction. Catabolism of additional sugar substrate, which may be required to generate this ATP, negatively affects product yields. Here, we review alternative pathways that can be engineered into yeast to optimize supply of cytosolic acetyl-CoA as a precursor for product formation. Particular attention is paid to reaction stoichiometry, free-energy conservation and redox-cofactor balancing of alternative pathways for acetyl-CoA synthesis from glucose. A theoretical analysis of maximally attainable yields on glucose of four compounds (n-butanol, citric acid, palmitic acid and farnesene) showed a strong product dependency of the optimal pathway configuration for acetyl-CoA synthesis. Moreover, this analysis showed that combination of different acetyl-CoA production pathways may be required to achieve optimal product yields. This review underlines that an integral analysis of energy coupling and redox-cofactor balancing in precursor-supply and product-formation pathways is crucial for the design of efficient cell factories.
Targeting cancer with a bi-functional peptide: in vitro and in vivo results. (2014)

We designed a bi-functional peptide of 23 amino acids and demonstrated its ability to bind and kill several cancer cell lines in vitro and to strongly increase survival in breast cancer bearing mice in vivo. This novel toxin could be used in future cancer therapies and warrants further pre-clinical and clinical exploration.
Integrated Affinity Capture, Purification, and Capillary Electrophoresis Microdevice for Quantitative Double-Stranded DNA Analysis (2007)

A novel injection method is developed that utilizes a thermally switchable oligonucleotide affinity capture gel to mediate the concentration, purification, and injection of dsDNA for quantitative microchip capillary electrophoresis analysis. The affinity capture matrix consists of a 20 base acrydite modified oligonucleotide copolymerized into a 6% linear polyacrylamide gel that captures ssDNA or dsDNA analyte including PCR amplicons and synthetic oligonucleotides. Double stranded PCR amplicons with complementarity to the capture probe up to 81 bases from their 5' terminus are reproducibly captured via helix invasion. By integrating the oligo capture matrix directly with the CE separation channel, the electrophoretically mobilized target fragments are quantitatively captured and injected after thermal release for unbiased, efficient, and quantitative analysis. The capture process exhibits optimal efficiency at 44 degrees C and 100 V/cm with a 20 microM affinity capture probe (TM = 57.7 degrees C). A dsDNA titration assay with 20 bp fragments validated that dsDNA is captured at the same efficiency as ssDNA. Dilution studies with a duplex 20mer show that targets can be successfully captured and analyzed with a limit of detection of 1 pM from 250 nL of solution (approximately 150,000 fluorescent molecules). Simultaneous capture and injection of amplicons from E. coli K12 and M13mp18 using a mixture of two different capture probes demonstrates the feasibility of multiplex target capture. Unlike the traditional cross-injector, this method enables efficient capture and injection of dsDNA amplicons which will facilitate the quantitative analysis of products from integrated nanoliter-scale PCR reactors.
Basic science and inherited retinal disease (1994)

This is a study of the retina, with new contributions by authoritative ophthalmologists. The three volumes cover all aspects of vitreoretinal disease from its pathophysiology to its treatment by medical and surgical measures. Volume 1 includes basic science, inherited retinal diseases and tumours; Volume 2 details medical retina; and Volume 3 surgical retina.
6-Mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity. (1996)

These results suggest that high performance liquid chromatography measurement of erythrocyte 6-MP metabolites may provide a quantitative assessment of patient responsiveness and compliance to treatment. The data support an immunosuppressive role for 6-TG, and potential cytotoxicity of raised 6-MMP levels.
RNA Processing and Export (2010)

Messenger RNAs undergo 5' capping, splicing, 3'-end processing, and export before translation in the cytoplasm. It has become clear that these mRNA processing events are tightly coupled and have a profound effect on the fate of the resulting transcript. This processing is represented by modifications of the pre-mRNA and loading of various protein factors. The sum of protein factors that stay with the mRNA as a result of processing is modified over the life of the transcript, conferring significant regulation to its expression.
Erratum: Energy Gaps in Graphene Nanoribbons [Phys. Rev. Lett.97, 216803 (2006)] (2007)

Received 2 February 2007DOI:https://doi.org/10.1103/PhysRevLett.98.089901©2007 American Physical Society
Dependence of noise-induced hearing loss upon perilymph magnesium concentration (1983)

Noise-induced hearing loss (NIHL) is significantly greater in rats fed a magnesium-deficient diet than in rats on a magnesium-rich diet. The hearing loss was found to be negatively correlated with the magnesium concentration of the perilymph. It is suggested that also in man, the magnesium concentration in the perilymph may be of importance in determining susceptibility to NIHL.