gebhart/patrepeval huggingface dataset:
Mechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin A (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanistic study on the inactivation of general acyl-CoA dehydrogenase by a metabolite of hypoglycin AMing Tain Lai, Li Da Liu, and Hung Wen LiuCite this: J. Am. Chem. Soc. 1991, 113, 19, 7388–7397Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September 1991https://pubs.acs.org/doi/10.1021/ja00019a040https://doi.org/10.1021/ja00019a040research-articleACS PublicationsRequest reuse permissionsArticle Views796Altmetric-Citations83LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Combinatorial Approaches Provide Fresh Leads for Medicinal Chemistry (1994)

RETURN TO ISSUEPREVNewsNEXTCombinatorial Approaches Provide Fresh Leads for Medicinal ChemistryNew ways of generating compounds provide vastly greater arrays of molecules that can be surveyed for biological activityRUDY M. BAUMView Author Information C&EN West Coast News BureauCite this: Chem. Eng. News 1994, 72, 6, 20–26Publication Date (Print):February 7, 1994Publication History Published online11 November 2010Published inissue 7 February 1994https://pubs.acs.org/doi/10.1021/cen-v072n006.p020https://doi.org/10.1021/cen-v072n006.p020newsACS PublicationsCopyright © 1994 AMERICAN CHEMICAL SOCIETYArticle Views24Altmetric-Citations29LEARN 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 InRedditEmail Other access options SUBJECTS:Medicinal chemistry Get e-Alerts
Chiari I Malformation Redefined: Clinical and Radiographic Findings for 364 Symptomatic Patients (1999)

These data support accumulating evidence that CMI is a disorder of the para-axial mesoderm that is characterized by underdevelopment of the posterior cranial fossa and overcrowding of the normally developed hindbrain. Tonsillar herniation of less than 5 mm does not exclude the diagnosis. Clinical manifestations of CMI seem to be related to cerebrospinal fluid disturbances (which are responsible for headaches, pseudotumor-like episodes, endolymphatic hydrops, syringomyelia, and hydrocephalus) and direct compression of nervous tissue. The demonstration of familial aggregation suggests a genetic component of transmission.
Amiloride Improves Locomotor Recovery after Spinal Cord Injury (2011)

Amiloride is a drug approved by the United States Food and Drug Administration, which has shown neuroprotective effects in different neuropathological conditions, including brain injury or brain ischemia, but has not been tested in spinal cord injury (SCI). We tested amiloride's therapeutic potential in a clinically relevant rat model of contusion SCI inflicted at the thoracic segment T10. Rats receiving daily administration of amiloride from 24 h to 35 days after SCI exhibited a significant improvement in hindlimb locomotor ability at 21, 28, and 35 days after injury, when compared to vehicle-treated SCI rats. Rats receiving amiloride treatment also exhibited a significant increase in myelin oligodendrocyte glycoprotein (MOG) levels 35 days after SCI at the site of injury (T10) when compared to vehicle-treated controls, which indicated a partial reverse in the decrease of MOG observed with injury. Our data indicate that higher levels of MOG correlate with improved locomotor recovery after SCI, and that this may explain the beneficial effects of amiloride after SCI. Given that amiloride treatment after SCI caused a significant preservation of myelin levels, and improved locomotor recovery, it should be considered as a possible therapeutic intervention after SCI.
Discovery of an Orally Available, Brain Penetrant BACE1 Inhibitor That Affords Robust CNS Aβ Reduction (2012)

Inhibition of BACE1 to prevent brain Aβ peptide formation is a potential disease-modifying approach to the treatment of Alzheimer's disease. Despite over a decade of drug discovery efforts, the identification of brain-penetrant BACE1 inhibitors that substantially lower CNS Aβ levels following systemic administration remains challenging. In this report we describe structure-based optimization of a series of brain-penetrant BACE1 inhibitors derived from an iminopyrimidinone scaffold. Application of structure-based design in tandem with control of physicochemical properties culminated in the discovery of compound 16, which potently reduced cortex and CSF Aβ40 levels when administered orally to rats.
A Glutaredoxin, Encoded by the G4L Gene of Vaccinia Virus, Is Essential for Virion Morphogenesis (2000)

Vaccinia virus encodes two glutaredoxins, O2L and G4L, both of which exhibit thioltransferase and dehydroascorbate reductase activities in vitro. Although O2L was previously found to be dispensable for virus replication, we now show that G4L is necessary for virion morphogenesis. RNase protection and Western blotting assays indicated that G4L was expressed at late times after infection and was incorporated into mature virus particles. Attempts to isolate a mutant virus with a deleted G4L gene were unsuccessful, suggesting that the protein was required for virus replication. This interpretation was confirmed by the construction and characterization of a conditional lethal recombinant virus with an inducible copy of the G4L gene replacing the original one. Expression of G4L was proportional to the concentration of inducer, and the amount of glutaredoxin could be varied from barely detectable to greater than normal amounts of protein. Immunogold labeling revealed that the induced G4L protein was associated with immature and mature virions and adjacent cytoplasmic depots. In the absence of inducer, the production of infectious virus was severely inhibited, though viral late protein synthesis appeared unaffected except for decreased maturation-dependent proteolytic processing of certain core components. Electron microscopy of cells infected under nonpermissive conditions revealed an accumulation of crescent membranes on the periphery of electron-dense globular masses but few mature particles. We concluded that the two glutaredoxin homologs encoded by vaccinia virus have different functions and that G4L has a role in virion morphogenesis, perhaps by acting as a redox protein.
Peroxisome Proliferator Activator Receptor-γ Ligands, 15-Deoxy-Δ12,14-Prostaglandin J2 and Ciglitazone, Reduce Systemic Inflammation in Polymicrobial Sepsis by Modulation of Signal Transduction Pathways (2003)

Peroxisome proliferator activator receptor-gamma (PPARgamma) is a nuclear receptor that controls the expression of several genes involved in metabolic homeostasis. We investigated the role of PPARgamma during the inflammatory response in sepsis by the use of the PPARgamma ligands, 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) and ciglitazone. Polymicrobial sepsis was induced by cecal ligation and puncture in rats and was associated with hypotension, multiple organ failure, and 50% mortality. PPARgamma expression was markedly reduced in lung and thoracic aorta after sepsis. Immunohistochemistry showed positive staining for nitrotyrosine and poly(ADP-ribose) synthetase in thoracic aortas. Plasma levels of TNF-alpha, IL-6, and IL-10 were increased. Elevated activity of myeloperoxidase was found in lung, colon, and liver, indicating a massive infiltration of neutrophils. These events were preceded by degradation of inhibitor kappaBalpha (IkappaBalpha), activation of IkappaB kinase complex, and c-Jun NH(2)-terminal kinase and, subsequently, activation of NF-kappaB and AP-1 in the lung. In vivo treatment with ciglitazone or 15d-PGJ(2) ameliorated hypotension and survival, blunted cytokine production, and reduced neutrophil infiltration in lung, colon, and liver. These beneficial effects of the PPARgamma ligands were associated with the reduction of IkappaB kinase complex and c-Jun NH(2)-terminal kinase activation and the reduction of NF-kappaB and AP-1 DNA binding in the lung. Furthermore, treatment with ciglitazone or 15d-PGJ(2) up-regulated the expression of PPARgamma in lung and thoracic aorta and abolished nitrotyrosine formation and poly(ADP-ribose) expression in aorta. Our data suggest that PPARgamma ligands attenuate the inflammatory response in sepsis through regulation of the NF-kappaB and AP-1 pathways.
A Clinical Review of the Association of Thyroid Stimulating Hormone and Cognitive Impairment (2013)

Clinical and subclinical hypothyroidism as well as overt hyperthyroidism in middle-aged and elderly adults are both associated with decreased cognitive functioning as memory, reaction time, and visuospatial organization. Subclinical hyperthyroidism (SH) or low serum concentrations of TSH concentrations have been associated with dementia in previous epidemiological studies, but the association in the elderly has not been established. There is little or no consensus regarding how thyroid function is associated with cognitive performance in the elderly. In this focused review, we have performed an examination between eleven studies from the last five years examining the association between thyroid function and cognitive performance in elderly people, a group who is overrepresented among individuals with minor abnormalities in serum TSH and thyroid hormone concentration. Six of the studies showed a consistent finding of an association between SH with cognitive impairment or dementia. In general, taking into account the largest and most powerfully designed studies, there is a strong body of evidence supporting the association between SH and cognitive impairment. The scarce number of publications on these topics indicates the need of more research especially regarding longitudinal and interventional studies thus hopefully enabling confirmation or rejection of causality between TSH abnormalities and dementia.
Reducing Damage to Si Substrates during Gate Etching Processes (2008)

The mechanism of formation of a "Si recess" that appears during gate poly-Si etching was studied. Hydrogen in HBr plasma penetrates through a thin gate oxide film and generates dislocated sites in the Si substrate. We developed a molecular dynamics (MD) simulation to clarify both the penetration depth of H and O and the dislocation of Si. The damage was successfully minimized by controlling the high energy peak in the ion energy distribution function (IEDF) to be lower than the threshold energy of ion penetration.
Nascent-peptide-mediated ribosome stalling at a stop codon induces mRNA cleavage resulting in nonstop mRNA that is recognized by tmRNA (2004)

Recent studies have established that tmRNA-mediated protein tagging occurs at stop codons depending on the C-terminal amino acid sequence of the nascent polypeptide immediately adjacent to those codons. We investigate here how the trans-translation at a stop codon occurs by using model crp genes encoding variants of cAMP receptor protein (CRP). We demonstrate that a truncated crp mRNA is efficiently produced along with a normal transcript from the model gene where tmRNA-mediated protein tagging occurs. The truncated crp mRNA was not detected in the presence of tmRNA, indicating that its degradation was facilitated by tmRNA. The major 3'-ends of the truncated crp mRNA in cells unable to express tmRNA were mapped at and near the stop codon. When RNA derived from the model crp-crr fusion gene was analyzed, crr mRNA was detected as a downstream cleavage product along with the upstream crp mRNA. These results are compatible with the hypothesis that ribosome stalling caused by the tagging-provoking sequences leads to endonucleolytic cleavage of mRNA around the stop codon, resulting in nonstop mRNA. In addition, the data are consistent with the view that mRNA cleavage is the cause of trans-translation at stop codons. Neither the bacterial toxin RelE nor the known major endoribonucleases are required for this cleavage, indicating that either other endoribonuclease(s) or the ribosome itself would be responsible for the mRNA cleavage in response to ribosome stalling caused by the particular nascent peptides.
Simultaneous formation of holographic surface relief gratings and volume phase gratings in photosensitive polymer (2019)

We report on secondary surface relief grating formation associated with holographic recording of volume phase gratings in epoxy-based, free-surface, volume holographic recording material, as well as in pure Epon SU-8 photoresist. Light-induced gratings are formed simultaneously by photo-triggered mass migration in the cause of component diffusion. Height profiles of surface relief gratings are compared with refractive index modulation profiles of corresponding volume phase gratings. Parasitic volume gratings and non-sinusoidal profiles are also investigated. Based on the correlation of volume and surface gratings, analysis of the height profiles allows conclusions to be drawn on the mechanisms of volume holographic grating formation.
Phycobilisomes of Porphyridium cruentum. Pigment analysis (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhycobilisomes of Porphyridium cruentum. Pigment analysisElisabeth Gantt and Claudia A. LipschultzCite this: Biochemistry 1974, 13, 14, 2960–2966Publication Date (Print):July 1, 1974Publication History Published online1 May 2002Published inissue 1 July 1974https://doi.org/10.1021/bi00711a027RIGHTS & PERMISSIONSArticle Views563Altmetric-Citations125LEARN 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 (1 MB) Get e-Alerts Get e-Alerts
Increased level of interleukin-13, but not interleukin-4 and interferon-γ in chronic rhinosinusitis with nasal polyps (2013)

IL-13 with high level of total IgE was observed in the patients with CRSwNP, which predisposes them to have concomitant asthma. IFN-γ seems to be down-regulated in the patients with CRSwNP, but could be over-expressed in the presence of aspirin intolerance.
Purification of nuclear and mitochondrial uracil-DNA glycosylase from rat liver. Identification of two distinct subcellular forms (1985)

Rat liver uracil-DNA glycosylase has been purified from nuclear extracts over 3000-fold to apparent homogeneity as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme is a monomeric protein with a polypeptide molecular weight of approximately 35 000. It has a native molecular weight of 33 000 as determined by gel filtration chromatography and a sedimentation coefficient of 2.6 S in glycerol gradients. The nuclear enzyme has an alkaline pH optimum and a pI value of 9.3. Nuclear uracil-DNA glycosylase catalyzes the release of free uracil from both single-stranded and double-stranded DNA with the former being the preferred substrate. The enzyme is unable to recognize dUTP, dUMP, or poly(dA-dT) containing a 3'-terminal uracil residue as a substrate. However, internalization of terminal uracil residues by limited chain elongation produced a substrate for the glycosylase. Another species of uracil-DNA glycosylase has been partially purified from mitochondria. This activity differs from the nuclear enzyme in that it has (i) distinctive chromatographic properties, (ii) a lower native molecular weight of 20 000 as determined by molecular sieving, (iii) a distinct NaCl inhibition profile, and (iv) a longer half-life during thermal denaturation.
Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. (1986)

A monoclonal antibody to the microtubule-associated protein tau (tau) labeled some neurofibrillary tangles and plaque neurites, the two major locations of paired-helical filaments (PHF), in Alzheimer disease brain. The antibody also labeled isolated PHF that had been repeatedly washed with NaDodSO4. Dephosphorylation of the tissue sections with alkaline phosphatase prior to immunolabeling dramatically increased the number of tangles and plaques recognized by the antibody. The plaque core amyloid was not stained in either dephosphorylated or nondephosphorylated tissue sections. On immunoblots PHF polypeptides were labeled readily only when dephosphorylated. In contrast, a commercially available monoclonal antibody to a phosphorylated epitope of neurofilaments that labeled the tangles and the plaque neurites in tissue did not label any PHF polypeptides on immunoblots. The PHF polypeptides, labeled with the monoclonal antibody to tau, electrophoresed with those polypeptides recognized by antibodies to isolated PHF. The antibody to tau-labeled microtubules from normal human brains assembled in vitro but identically treated Alzheimer brain preparations had to be dephosphorylated to be completely recognized by this antibody. These findings suggest that tau in Alzheimer brain is an abnormally phosphorylated protein component of PHF.
Development of an In Vitro Bioassay for Clostridium botulinum Type B Neurotoxin in Foods That Is More Sensitive than the Mouse Bioassay (1999)

A novel, in vitro bioassay for detection of the botulinum type B neurotoxin in a range of media was developed. The assay is amplified by the enzymic activity of the neurotoxin's light chain and includes the following three stages: first, a small, monoclonal antibody-based immunoaffinity column captures the toxin; second, a peptide substrate is cleaved by using the endopeptidase activity of the type B neurotoxin; and finally, a modified enzyme-linked immunoassay system detects the peptide cleavage products. The assay is highly specific for type B neurotoxin and is capable of detecting type B toxin at a concentration of 5 pg ml(-1) (0.5 mouse 50% lethal dose ml(-1)) in approximately 5 h. The format of the test was found to be suitable for detecting botulinum type B toxin in a range of foodstuffs with a sensitivity that exceeds the sensitivity of the mouse assay. Using highly specific monoclonal antibodies as the capture phase, we found that the endopeptidase assay was capable of differentiating between the type B neurotoxins produced by proteolytic and nonproteolytic strains of Clostridium botulinum type B.
Localization of human factor FVIII inhibitor epitopes to two polypeptide fragments. (1985)

Epitopes for 22 alloantibodies that inhibit factor VIII procoagulant protein (FVIII) from multitransfused individuals with severe hemophilia A and three autoantibodies from nonhemophilic individuals appeared to be restricted to two specific regions of the FVIII molecule. Immunoblotting of purified FVIII and purified thrombin-degraded FVIII, followed by reaction with inhibitor plasma samples, monoclonal anti-human IgG3 and IgG4 antibodies, and radiolabeled affinity-purified rabbit anti-mouse IgG, revealed that inhibitor epitopes could be localized to the Mr 72,000 and Mr 44,000 thrombin fragments of FVIII. These two chains are located at the carboxyl terminus and near the amino terminus of the FVIII molecule, respectively. The pattern of reactivity of the inhibitor alloantibodies could be divided into three types: 10 reacted with the Mr 72,000 chain, 3 reacted with the Mr 44,000 chain, and 9 reacted with both of these chains. Among the 3 inhibitor autoantibodies, 1 of each type was found. Ten normal plasmas, as well as 14 plasmas from multitransfused individuals with severe hemophilia A and no inhibitor, were not reactive with the FVIII immunoblots. However, one multitransfused individual with severe hemophilia A and no detectable inhibitor revealed the presence of an antibody reactive with the middle section of the FVIII molecule. The existence of FVIII inhibitor epitopes on both the Mr 72,000 and Mr 44,000 chains raises the possibility that these epitopes might be further restricted to regions of homology between the two chains. These data suggest the possibility of designing inhibitor blocking polypeptides for use as therapeutic agents.
Expression of human recombinant 72 kDa gelatinase and tissue inhibitor of metalloproteinase-2 (TIMP-2): characterization of complex and free enzyme (1993)

The human 72 kDa gelatinase/type IV collagenase is a metalloproteinase that is thought to play a role in metastasis and angiogenesis. The 72 kDa progelatinase can be isolated from conditioned media as a complex with the tissue inhibitor of metalloproteinase-2 (TIMP-2). To investigate 72 kDa gelatinase-TIMP-2 interactions and to compare the activity of the complex versus that of the free enzyme, we have expressed and purified human 72 kDa progelatinase and TIMP-2 as single proteins in a recombinant vaccinia virus mammalian cell expression system. The recombinant 72 kDa progelatinase was able to bind TIMP-2, and it digested gelatin and collagen type IV after activation by p-aminophenylmercuric acid (APMA). The specific activity of the recombinant free enzyme was 20-fold higher than the activity of an APMA-treated stoichiometric complex of recombinant 72 kDa progelatinase and TIMP-2. Also, TIMP-2 caused an 86% inhibition of activity when added to the activated enzyme at a 1:1 molar ratio. Activation of the free recombinant 72 kDa progelatinase yielded the 62 kDa species and two fragments of 46 and 35 kDa that cross-reacted with monoclonal antibodies to the 72 kDa proenzyme. TIMP-2 inhibited the conversion of the recombinant proenzyme to the 62 kDa species and the appearance of the 45 and 35 kDa bands. These results suggest that TIMP-2 is not only a potent inhibitor of the activated enzyme but also prevents the generation of low-molecular-mass species and full enzymic activity from the zymogen.