gebhart/patrepeval huggingface dataset:
Intracellular Fragments of the Natriuretic Peptide Receptor-C (NPR-C) Attenuate Dopamine Efflux* (1999)

Natriuretic peptides suppress adrenergic neurotransmission by a mechanism apparently involving the natriuretic peptide receptor-C (NPR-C) rather than particulate guanylyl cyclase receptors. The bulk of evidence implicating the NPR-C in neuromodulatory effects relies on the pharmacological specificity of peptides believed to be specific for the NPR-C. This study tests for NPR-C effects on neurotransmitter release by examining fragments of the receptor for biological activity in pheochromocytoma (PC12) cells permeabilized with digitonin. A pentadecapeptide segment of the cytoplasmic portion of the NPR-C mimicked the effect of natriuretic peptides to suppress dopamine efflux evoked by calcium approximately 40%. Furthermore, an antibody generated against the pentadecapeptide fragment abolished the neuromodulatory effect of C-type natriuretic peptide in permeabilized cells. In contrast, the carboxy terminal nonadecapeptide portion of the NPR-C failed to attenuate dopamine efflux. These data are consistent with the proposed role of the NPR-C in transducing the biological activity of natriuretic peptides in adrenergic tissue. The most novel aspect of these observations involves the potency of the small cytosolic region of the NPR-C with the region closest to the membrane accounting for neuromodulatory effects.
Delivery of α - and β -Sarcoglycan by Recombinant Adeno-Associated Virus: Efficient Rescue of Muscle, but Differential Toxicity (2002)

The sarcoglycanopathies are a group of four autosomal recessive limb girdle muscular dystrophies (LGMD 2D, 2E, 2C, and 2F), caused by mutations of the alpha-, beta-, gamma-, or delta-sarcoglycan genes, respectively. The delta-sarcoglycan-deficient hamster has been the most utilized model for gene delivery to muscle by recombinant adeno-associated virus (AAV) vectors; however, human patients with delta-sarcoglycan deficiency are exceedingly rare, with only two patients described in the United States. Here, we report construction and use of AAV vectors expressing either alpha- or beta-sarcoglycan, the genes responsible for the most common forms of the human sarcoglycanopathies. Both vectors showed successful short-term genetic, biochemical, and histological rescue of both alpha- and beta-sarcoglycan-deficient mouse muscle. However, comparison of persistence of expression in 51 injected mice showed substantial differences between AAV alpha-sarcoglycan (alpha-SG) and beta-sarcoglycan (beta-SG) vectors. AAV-beta-SG showed long-term expression with no decrease in expression for more than 21 months after injection, whereas AAV-alpha-SG showed a dramatic loss of positive fibers between 28 and 41 days post-injection (p = 0.006). Loss of immunopositive myofibers was correlated with significant inflammatory cell infiltrate, primarily macrophages. To determine whether the loss of alpha-sarcoglycan-positive fibers was due to an immune response or cytotoxic effect of alpha-sarcoglycan overexpression, severe combined immunodeficient (SCID) mouse muscle was assayed for cytotoxicity after injection with AAV-alpha-SG, AAV-beta-SG, or phosphate-buffered saline. The results were consistent with overexpression of alpha-sarcoglycan causing significant cytotoxicity. The cytotoxicity of alpha-sarcoglycan, and not beta- or delta-sarcoglycan overexpression, was consistent with biochemical studies of the hierarchical order of assembly of the sarcoglycan complex. Our data suggest that even closely related proteins might require different levels of expression to avoid toxicity and achieve long-term tissue rescue.
The Optic Nerve Head in Glaucomatous Optic Neuropathy (1997)

Primary open-angle glaucoma, the most common form of glaucoma, is characterized by irreversible loss of axons from the optic nerve. Previous research in humans and monkeys with glaucoma suggests that the site of damage to the axons is at the level of the lamina cribrosa in the optic nerve head. In the glaucomatous optic nerve head, progressive cupping of the optic disc results from compression, stretching, and remodeling of the connective tissue (extracellular matrix) of the lamina cribrosa. Astrocytes are the major cell type in the optic nerve and may participate actively in the remodeling of the extracellular matrix. There may be individual variability in the composition, structure, or reactive processes of the tissue supporting the axons in the optic nerve that may explain the variations in the nature and degree of cupping in response to intraocular pressure and in the progression of the neuropathy. We present evidence of specific changes in the extracellular matrix of the lamina cribrosa and the role of astrocytes in glaucomatous optic neuropathy. Future studies focused on developing therapies directed at preventing or controling damage to the extracellular matrix may help improve the outcome of the management of glaucoma.
Egr-1 negatively regulates human tumor cell growth via the DNA-binding domain. (1995)

Human HT1080 fibrosarcoma cells, subclone H4, express little or no Egr-1 (Zif/268, Krox 24), an early growth response gene encoding a transcription factor. Phorbol ester (but not serum) treatment only can elicit a small increase in Egr-1 expression in H4, in contrast to the normally rapid, high transient expression of Egr-1 observed after the addition of a wide range of stimulating agents to normal or immortalized cell lines. Because several human tumor cell lines express little Egr-1, we tested the hypothesis that this loss was causal to transformation. We report here that the expression of exogenous mouse Egr-1 in H4 cells inhibits transformed growth in a dose-dependent manner and significantly suppresses tumorigenicity in athymic mice. By overexpression of the fragment in Egr-1 that is responsible for its DNA-binding activity, the zinc-finger domain, we show that this domain has a similar activity. Moreover, the expression of antisense mRNA encoding the DNA-binding domain increases the transformed character of the H4 cells. One possible conclusion is that endogenous Egr-1-like genes perform growth-regulatory functions. Other human tumor lines are also growth suppressed by Egr-1 overexpression including ZR-75-1 breast carcinoma, U251 glioblastoma, and to a lesser extent, SAOS-2 osteosarcoma cells. These results are surprising in light of the "early growth response" character of Egr-1 but extend our earlier report of suppression of growth in v-sis-transformed NIH3T3 cells.
cDNA Cloning, Expression, and Mutagenesis of Scytalone Dehydratase Needed for Pathogenicity of the Rice Blast Fungus, Pyricularia oryzae. (1998)

We purified scytalone dehydratase from the rice blast fungus, Pyricularia oryzae, and cloned its cDNA on the basis of its amino acid sequence. The deduced amino acid sequence was 62% identical to the scytalone dehydratase from Colletotrichum lagenarium. The expression of this gene was induced transcriptionally in the stationary phase when melanin synthesis occurs. We constructed a heterologous expression system for the enzyme in Escherichia coli, did deletion analysis with this system, and found that a C-terminal region is essential for the enzyme function.
Grubbs’ Ruthenium-Carbenes Beyond the Metathesis Reaction: Less Conventional Non-Metathetic Utility (2009)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTGrubbs' Ruthenium-Carbenes Beyond the Metathesis Reaction: Less Conventional Non-Metathetic UtilityBenito Alcaide*†, Pedro Almendros*‡, and Amparo Luna†View Author Information Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense de Madrid, 28040 Madrid, Spain, and Instituto de Química Orgánica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain* E-mail: [email protected]; [email protected]†Universidad Complutense de Madrid.‡CSIC.Cite this: Chem. Rev. 2009, 109, 8, 3817–3858Publication Date (Web):July 2, 2009Publication History Received13 April 2009Published online2 July 2009Published inissue 12 August 2009https://doi.org/10.1021/cr9001512Copyright © 2009 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views9338Altmetric-Citations289LEARN 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 Read OnlinePDF (2 MB) Get e-AlertscloseSUBJECTS:Carbene compounds,Catalysts,Hydrocarbons,Isomerization,Metathesis Get e-Alerts
Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity (2009)

Current influenza A virus vaccines do not generate significant immunity against serologically distinct influenza A virus subtypes and would thus be ineffective in the face of a pandemic caused by a novel variant emerging from, say, a wildlife reservoir. One possible solution would be to modify these vaccines so that they prime cross-reactive CD8(+) cytotoxic T lymphocytes (CTL) cell-mediated immunity directed at conserved viral epitopes. A further strategy is to use novel adjuvants, such as the immunomodulatory glycolipid alpha-galactosylceramide (alpha-GalCer). We show here that giving alpha-GalCer with an inactivated influenza A virus has the paradoxical effect of diminishing acute CTL immunity via natural killer T (NKT) cell-dependent expression of indoleamine 2,3-dioxygenase (IDO), an important mediator of immune suppression, while at the same time promoting the survival of long-lived memory CTL populations capable of boosting protection against heterologous influenza A virus challenge. This enhancement of memory was likely due to the alpha-GalCer-induced upregulation of prosurvival genes, such as bcl-2, and points to the potential of alpha-GalCer as an adjuvant for promoting optimal, vaccine-induced CD8(+) T cell memory.
Structure–function relationships in the catalytic and starch binding domains of glucoamylase (1994)

Sixteen primary sequences from five sub-families of fungal, yeast and bacterial glucoamylases were related to structural information from the model of the catalytic domain of Aspergillus awamori var. X100 glucoamylase obtained by protein crystallography. This domain is composed of thirteen alpha-helices, with five conserved regions defining the active site. Interactions between methyl alpha-maltoside and active site residues were modelled, and the importance of these residues on the catalytic action of different glucoamylases was shown by their presence in each primary sequence. The overall structure of the starch binding domain of some fungal glucoamylases was determined based on homology to the C-terminal domains of Bacillus cyclodextrin glucosyl-transferases. Crystallography indicated that this domain contains 6-8 beta-strands and homology allowed the attribution of a disulfide bridge in the glucoamylase starch binding domain. Glucoamylase residues Thr525, Asn530 and Trp560, homologous to Bacillus stearothermophilus cyclodextrin glucosyltransferase residues binding to maltose in the C-terminal domain, could be involved in raw-starch binding. The structure and length of the linker region between the catalytic and starch binding domains in fungal glucoamylases can vary substantially, a further indication of the functional independence of the two domains.
Bidirectional MC-EZBC With Lifting Implementation (2004)

In conventional motion-compensated three-dimensional subband/wavelet coding, where the motion compensation is unidirectional, incorrect classification of connected and unconnected pixels caused by incorrect motion vectors (MVs) has resulted in some coding inefficiency and visual artifacts in the embedded low-frame-rate video. In this paper, we introduce bidirectional motion compensated temporal filtering with unconnected pixel detection and I blocks. We also incorporate a recently suggested lifting implementation of the subband/wavelet filter for improved MV accuracy in an MC-EZBC coder. Simulation results compare PSNR performance of this new version of MC-EZBC versus H.26L under the constraint of equal groups of pictures size, and show a general parity with this state-of-the-art nonscalable coder on several test clips.
Inhibitors of AP-1 and NF-&#954;B Mediated Transcriptional Activation: Therapeutic Potential in Autoimmune Diseases and Structural Diversity (2002)

Cytokines and chemokines play a very important role in a number of inflammatory diseases. In activated T cells, transcription factors such as the activator protein-1 (AP-1) regulate IL-2 production and production of matrix metalloproteinases, the nuclear factor kappa B (NF-kappa B) is essential for the transcriptional regulation of the proinflammatory cytokines IL-1, IL-6, IL-8 and TNF alpha, and nuclear factor of activated T-cells (NFAT) is required for the transcriptional regulation of IL-2, IL-3, IL-4, IL-5, IL-8, IL-13, TNF alpha, and GM-CSF. During the last few years, several groups have developed inhibitors of AP-1, NF-kappa B or both, and NFAT. This review article presents the recent progress in the development of inhibitors for AP-1, NF-kappa B, and NFAT mediated transcriptional activation.
Line Probe Assay for Monitoring Drug Resistance in Hepatitis B Virus-Infected Patients during Antiviral Therapy (2000)

Since the introduction of antiviral compounds such as lamivudine and famciclovir in the treatment schedules of patients with chronic hepatitis B virus (HBV) infection, the accumulation of a variety of mutations in the HBV polymerase gene has been observed. The selection of these mutations is generally considered the cause of viral nonresponsiveness and treatment failure. Therefore, the detection of these mutations is of clinical importance. Previously genotyped HBV strains isolated from treated and untreated patients were amplified with primers specific for the HBV polymerase region from amino acids 465 to 562. Amplified products were cloned into plasmid vectors. The clones were used as reference strains. A set of 38 highly specific oligonucleotide probes covering three different codon positions, L528M, M552V/I, and V/L/M555I, were selected. These probes were applied as 19 different lines on a membrane strip. The strips were then hybridized with PCR fragments from the reference panel, revealing the amino acids at the three codon positions simultaneously for each clone. PCR products generated from two patients infected with HBV genotypes A and C, respectively, and treated with nucleoside analogs were analyzed on these strips. A gradual increase in genetic HBV polymerase complexity was observed in follow-up samples compared to that in pretreatment samples. Additional analysis of HBV polymerase DNA fragments in recombinant plasmid clones demonstrated the existence of (i) clones with double mutations, (ii) clones with single mutations at either codon 528, 552, or 555, and (iii) the simultaneous occurrence of two or more viral populations within one sample. This line probe assay detected the complex quasispecies nature of HBV and provided some insight into the dynamics of resistance mutations.
Human daily activity recognition in robot-assisted living using multi-sensor fusion (2009)

In this paper, we propose a human activity recognition method by fusing the data from two wearable inertial sensors attached to one foot and the waist of a human subject, respectively. Our multi-sensor fusion based method combines neural networks and hidden Markov models (HMMs), and can reduce the computation load. We conducted experiments using a prototype wearable sensor system and the obtained results prove the effectiveness and the accuracy of our algorithm.
Inhibition of Nitric Oxide Synthase in Experimental Gram-Negative Sepsis (1994)

Nitric oxide (NO) has been proposed as a mediator of hypotension in septic shock. The aim of this study was to determine whether an inhibitor of NO production, NG-monomethyl-L-arginine (L-NMMA), was able to protect against death in two murine models of experimental gram-negative sepsis. L-NMMA (3-300 mg kg-1) did not improve survival in intravenous or intraperitoneal models of sepsis. Seven h after intravenous infection, L-NMMA (100 mg/kg-1) reduced serum nitrite plus nitrate levels (NO breakdown products) from 774 microM in control-treated animals to 282 microM in L-NMMA-treated animals (P < .001). This compared to a level of 103 microM in uninfected mice. L-NMMA produced little change in bacterial load following infection and did not increase hepatic damage, as measured by serum levels of ornithine carbamoyltransferase. Thus, while L-NMMA may reverse the hyporesponsiveness of peripheral circulation in sepsis, it was unable to prevent death in these models of gram-negative septic shock.
Long-term outcome of individuals with pure red cell aplasia and antierythropoietin antibodies in patients treated with recombinant epoetin: a follow-up report from the Research on Adverse Drug Events and Reports (RADAR) Project (2005)

Since its introduction in 1988, recombinant human erythropoietin (epoetin) has been standard treatment for patients with anemia due to chronic kidney disease. From 1998 to 2004, nearly 200 epoetin-treated persons with chronic kidney disease developed antibodies to epoetin, resulting in pure red cell aplasia (PRCA). The majority of these patients received Eprex, an epoetin alfa product marketed exclusively outside the United States. Herein, we report on the long-term outcome of these individuals. For 170 chronic kidney disease patients who developed epoetin-associated PRCA and had 3 months or more follow-up information available, case reports from the Food and Drug Administration and epoetin manufacturers were reviewed for information on clinical characteristics of the patients, immunosuppressive treatments, epoetin responsiveness, and hematologic recovery. Overall, 64% of the PRCA patients received immunosuppressive therapy, including 19 who also underwent a renal transplantation. Thirty-seven percent experienced a hematologic recovery, with higher hematologic recovery rates among PRCA patients who received immunosuppressive therapy (57% vs 2%, P < .001). Among 34 patients who received epoetin after the onset of PRCA, 56% regained epoetin responsiveness. The highest rates of epoetin responsiveness were observed among persons whose antierythropoietin antibodies were undetectable when epoetin was administered (89%). Among chronic kidney disease patients with epoetin-associated PRCA, epoetin discontinuation and immunosuppressive therapy or renal transplantation is necessary for hematologic recovery. Reinitiation of epoetin therapy among individuals could be considered if antierythropoietin antibodies are undetectable.
Radical Addition to 1,4-Benzoquinones:  Addition at O- versus C-Atom (2006)

Addition of alkyl radicals generated from B-alkylcatecholboranes onto 1,4-benzoquinones leads to substituted hydroquinones in good overall yields. Formation of aryl ethers via a unique radical addition to the oxygen atom of the enone system is the main reaction when bulky secondary and tertiary alkyl radicals are used. Less hindered secondary and primary radicals give the expected 1,4-conjugate addition products. [reaction: see text]
Selective Induction of Cell Death in Melanoma Cell Lines through Targeting of Mcl-1 and A1 (2012)

Melanoma is an often fatal form of skin cancer which is remarkably resistant against radio- and chemotherapy. Even new strategies that target RAS/RAF signaling and display unprecedented efficacy are characterized by resistance mechanisms. The targeting of survival pathways would be an attractive alternative strategy, if tumor-specific cell death can be achieved. Bcl-2 proteins play a central role in regulating survival of tumor cells. In this study, we systematically investigated the relevance of antiapoptotic Bcl-2 proteins, i.e., Bcl-2, Bcl-xL, Bcl-w, Mcl-1, and A1, in melanoma cell lines and non-malignant cells using RNAi. We found that melanoma cells required the presence of specific antiapoptotic Bcl-2 proteins: Inhibition of Mcl-1 and A1 strongly induced cell death in some melanoma cell lines, whereas non-malignant cells, i.e., primary human fibroblasts or keratinocytes were not affected. This specific sensitivity of melanoma cells was further enhanced by the combined inhibition of Mcl-1 and A1 and resulted in 60% to 80% cell death in all melanoma cell lines tested. This treatment was successfully combined with chemotherapy, which killed a substantial proportion of cells that survived Mcl-1 and A1 inhibition. Together, these results identify antiapoptotic proteins on which specifically melanoma cells rely on and, thus, provide a basis for the development of new Bcl-2 protein-targeting therapies.
Single-Molecule Surface-Enhanced Raman Spectroscopy (2012)

A general overview of the field of single-molecule (SM) surface-enhanced Raman spectroscopy (SERS) as it stands today is provided. After years of debates on the basic aspects of SM-SERS, the technique is emerging as a well-established subfield of spectroscopy and SERS. SM-SERS is allowing the observation of subtle spectroscopic phenomena that were not hitherto accessible. Examples of the latter are natural isotopic substitutions in single molecules, observation of the true homogeneous broadening of Raman peaks, Raman excitation profiles of individual molecules, and SM electrochemistry. With background examples of the contributions produced by our group, properly interleaved with results by other practitioners in the field, we present some of the latest developments and promising new leads in this new field of spectroscopy.
Structure of the antibiotic ristocetin A (1979)

D. H. Williams, V. Rajananda, G. Bojesen and M. P. Williamson, J. Chem. Soc., Chem. Commun., 1979, 906 DOI: 10.1039/C39790000906
Ketamine Infusions for Treatment Refractory Headache (2016)

Subanesthetic ketamine infusions may be beneficial in individuals with CM or NDPH who have failed other aggressive treatments. Controlled trials may confirm this, and further studies may be useful in elucidating more robust benefit in a less refractory patient population.