gebhart/patrepeval huggingface dataset:
Structural characterization of a chain termination mutant of human serum albumin. (1986)

Mutant forms of human serum albumin have been detected on the basis of their abnormal electrophoretic mobility which is either faster or slower than that of normal albumin. In the present work we have studied the structure of a slow variant, referred to as albumin Ge/Ct, in order to define the cause of its genetic abnormality. The protein was isolated from the serum of a young healthy woman homozygous for the variant. Analysis of CNBr fragments by isoelectric focusing allowed us to localize the mutation to the COOH-terminal region of the molecule (residues 549-585). This fragment was isolated on a preparative scale and subjected to tryptic digestion. All tryptic peptides were purified by reverse-phase high performance liquid chromatography and characterized. Sequential analysis of three abnormal peptides revealed that albumin Ge/Ct has a shortened chain with the following COOH-terminal sequence: Leu-Val-Ala-Ala-Ser-Lys580-Leu-Pro. The presence of an additional lysine residue accounts for the electrophoretic behavior of the variant. It is likely that the variant may be caused by a single base deletion in the structural gene, a Cyt in mRNA codon 580, and the consequent shift in reading frame.
Purification, cloning, and primary structure of a new enantiomer-selective amidase from a Rhodococcus strain: structural evidence for a conserved genetic coupling with nitrile hydratase (1991)

A new enantiomer-selective amidase active on several 2-aryl propionamides was identified and purified from a newly isolated Rhodococcus strain. The characterized amidase is an apparent homodimer, each molecule of which has an Mr of 48,554; it has a specific activity of 16.5 mumol of S(+)-2-phenylpropionic acid formed per min per mg of enzyme from the racemic amide under our conditions. An oligonucleotide probe was deduced from limited peptide information and was used to clone the corresponding gene, named amdA. As expected, significant homologies were found between the amino acid sequences of the enantiomer-selective amidase of Rhodococcus sp., the corresponding enzyme from Brevibacterium sp. strain R312, and several known amidases, thus confirming the existence of a structural class of amidase enzymes. Genes probably coding for the two subunits of a nitrile hydratase, albeit in an inverse order, were found 39 bp downstream of amdA, suggesting that such a genetic organization might be conserved in different microorganisms. Although we failed to express an active Rhodococcus amidase in Escherichia coli, even in conditions allowing the expression of an active R312 enzyme, the high-level expression of the active recombinant enzyme could be demonstrated in Brevibacterium lactofermentum by using a pSR1-derived shuttle vector.
New Light on an Old Story:  The Solid-State Transformation of Ammonium Cyanate into Urea (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTNew Light on an Old Story: The Solid-State Transformation of Ammonium Cyanate into UreaJack D. Dunitz, Kenneth D. M. Harris, Roy L. Johnston, Benson M. Kariuki, Elizabeth J. MacLean, Katerina Psallidas, W. Bernd Schweizer, and Rik R. TykwinskiView Author Information Organic Chemistry Laboratory Swiss Federal Institute of Technology ETH-Zentrum, CH-8092 Zürich, Switzerland School of Chemistry, University of Birmingham Edgbaston, Birmingham B15 2TT, United Kingdom Daresbury Laboratory, Warrington Cheshire WA4 4AD, United Kingdom Department of Chemistry, University of Alberta Edmonton, Alberta T6G 2G2, Canada Cite this: J. Am. Chem. Soc. 1998, 120, 50, 13274–13275Publication Date (Web):December 4, 1998Publication History Received15 September 1998Published online4 December 1998Published inissue 1 December 1998https://pubs.acs.org/doi/10.1021/ja983285chttps://doi.org/10.1021/ja983285crapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views466Altmetric-Citations36LEARN 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 SUBJECTS:Cations,Crystal structure,Granular materials,Inorganic carbon compounds,Urea Get e-Alerts
Systematic Replacement of Amino Acid Residues within an Arg-Gly-Asp-containing Loop of Foot-and-Mouth Disease Virus and Effect on Cell Recognition (1996)

The conserved Arg-Gly-Asp (RGD) motif found in a hypervariable, mobile antigenic loop of foot-and-mouth disease virus (FMDV) is critically involved in virus attachment to cells by binding to an integrin, probably related to alphavbeta3. Here we describe (i) the synthesis of 241 15-mer peptides, which represent this loop of FMDV (isolate C-S8c1) and single variants in which each amino acid residue was replaced by 16 others and (ii) the inhibitory activity of these peptides on the ability of FMDV C-S8c1 to recognize and infect susceptible cells. This approach has allowed a first detailed evaluation of the specificity of each residue within a RGD-containing protein loop on cell recognition. The results indicate that, in addition to the exquisitely specific RGD triplet, two highly conserved Leu residues located at positions +1 and +4 downstream of the RGD and, to a lesser extent, the residue at position +2 are the only critical and specific determinants within the loop in promoting cell recognition of a viral ligand. The results support the proposal that, in spite of their involvement in antibody recognition, RGD and other FMDV loop residues are remarkably conserved because of their essential role in cell recognition.
An optical-label controlled packet router for IP-over-WDM networks (2001)

A novel two-level optical labeling method for highly efficient transport of IP packets through WDM networks is proposed. By assigning both a wavelength label and a label in DPSK or FSK format (orthogonal to the ASK format of the data payload), packets can be routed transparently through end-to-end optical paths. The design of a duallabel controlled optical router is presented, which features label swapping and multicasting. Key element is an optically integrated wavelength converter and phase modulator. This work is part of the new IST project STOLAS – Switching Technologies for Optically Labeled Signals.
Ultrasound exposure in diagnostic echography. (1983)

The output characteristics and spatial distribution of pulses were studied in static and real time B-mode imaging, and M-mode procedures to assess the ultrasound exposure occurring over the total examination area and at a single point tissue target during a diagnostic examination.
Analytical procedure for use of conductance measurement to estimate Escherichia coli in shellfish (1994)

Assays were performed with a Malthus AT Microbiological Analyzer to define an analytical procedure to estimate Escherichia coli counts in live bivalve shellfish by conductance measurement. The growth conditions used (Malthus Coliform Broth at 44 degrees C) were selective for E. coli, and interference was noted only when Klebsiella pneumoniae were at least 100 times as numerous as E. coli. Different sample preparation procedures and seeding conditions were tested to obtain good quality conductance curves. The best results were observed when: (a) meat and shell liquor were diluted 1:3 with tryptone salt water and homogenized in a Waring blender for 1 min at 15,000 rev min-1; and (b) the inoculum was taken from the liquid phase of the homogenate 20 min after blending and mixed immediately with the culture medium. Detection parameter threshold values were adjusted (first difference 1.5 microS for the baseline and 3.5 microS for detection, second difference 0.2 microS) to improve detection time reliability. The repeatability of conductance measurements was very good (S.D. as % response mean ranged from 1.9 to 3.3) with the protocol used.
Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics (1989)

Serial electron microscopy and 3-D reconstructions of dendritic spines from hippocampal area CA 1 dendrites were obtained to evaluate 2 questions about relationships between spine geometry and synaptic efficacy. First, under what biophysical conditions are the spine necks likely to reduce the magnitude of charge transferred from the synapses on the spine heads to the recipient dendrite? Simulation software provided by Charles Wilson (1984) was used to determine that if synaptic conductance is 1 nS or less, only 1% of the hippocampal spine necks are sufficiently thin and long to reduce charge transfer by more than 10%. If synaptic conductance approaches 5 nS, however, 33% of the hippocampal spine necks are sufficiently thin and long to reduce charge transfer by more than 10%. Second, is spine geometry associated with other anatomical indicators of synaptic efficacy, including the area of the postsynaptic density and the number of vesicles in the presynaptic axon? Reconstructed spines were graphically edited into head and neck compartments, and their dimensions were measured, the areas of the postsynaptic densities (PSD) were measured, and all of the vesicles in the presynaptic axonal varicosities were counted. The dimensions of the spine head were well correlated with the area of PSD and the number of vesicles in the presynaptic axonal varicosity. Spine neck diameter and length were not correlated with PSD area, head volume, or the number of vesicles. These results suggest that the dimensions of the spine head, but not the spine neck, reflect differences in synaptic efficacy. We suggest that the constricted necks of hippocampal dendritic spines might reduce diffusion of activated molecules to neighboring synapses, thereby attributing specificity to activated or potentiated synapses.
Spermine Oxidase SMO(PAOh1), Not N1-Acetylpolyamine Oxidase PAO, Is the Primary Source of Cytotoxic H2O2 in Polyamine Analogue-treated Human Breast Cancer Cell Lines (2005)

The induction of polyamine catabolism and its production of H2O2 have been implicated in the response to specific antitumor polyamine analogues. The original hypothesis was that analogue induction of the rate-limiting spermidine/spermine N1-acetyltransferase (SSAT) provided substrate for the peroxisomal acetylpolyamine oxidase (PAO), resulting in a decrease in polyamine pools through catabolism, oxidation, and excretion of acetylated polyamines and the production of toxic aldehydes and H2O2. However, the recent discovery of the inducible spermine oxidase SMO(PAOh1) suggested the possibility that the original hypothesis may be incomplete. To examine the role of the catabolic enzymes in the response of breast cancer cells to the polyamine analogue N1,N1-bis(ethyl)norspermine (BENSpm), a stable knockdown small interfering RNA strategy was used. BENSpm differentially induced SSAT and SMO(PAOh1) mRNA and activity in several breast cancer cell lines, whereas no N1-acetylpolyamine oxidase PAO mRNA or activity was detected. BENSpm treatment inhibited cell growth, decreased intracellular polyamine levels, and decreased ornithine decarboxylase activity in all cell lines examined. The stable knockdown of either SSAT or SMO(PAOh1) reduced the sensitivity of MDA-MB-231 cells to BENSpm, whereas double knockdown MDA-MB-231 cells were almost entirely resistant to the growth inhibitory effects of the analogue. Furthermore, the H2O2 produced through BENSpm-induced polyamine catabolism was found to be derived exclusively from SMO(PAOh1) activity and not through PAO activity on acetylated polyamines. These data suggested that SSAT and SMO(PAOh1) activities are the major mediators of the cellular response of breast tumor cells to BENSpm and that PAO plays little or no role in this response.
P2‐478: Discovery and in vivo evaluation of potent 5‐HT6 receptor antagonists for cognition enhancement in treating Alzheimer's disease (2008)

5-HT6 receptors are expressed in the brain regions associated with learning and memory, and blockade of their function increases central cholinergic and glutamatergic neurotransmission and enhances cognitive processes. We report the development of a novel, aqueous-soluble, safe, BBB penetrant potent series of small molecule antagonists of 5-HT6 receptors in a series of new Dimebon analogs. Recently Dimebon was reported to have met all five efficacy endpoints in a one-year randomized, double-blind, placebo-controlled phase II study of ∼200 patients with mild to moderate Alzheimer's Disease. We were the first to show that Dimebon is a potent 5-HT6 antagonist (Ki = 70 nM) and selected this drug as a starting point for the design of novel drug-like chemotypes. The design, synthesis, and SAR studies included tri- and bicyclic “core” and/or “decoration” variations of chemical structure in several consecutive iterations. Cognition disorders perhaps due to their unique intricacy have not benefited from rational single-targeted drug design. In response to this challenge we have selected a few key biotargets for specific modulation. The “constellation” of 5-HT6, 5-HT2C, AChE, Ca L-channel, NMDA, etc. was chosen as desirable for inhibition (antagonism), and hERG, 5-HT2B (“black holes”) were identified as undesirable. SAR data will be demonstrated around the lead series to illustrate the improvements in targeting affinities at multiple biomolecules. Hit-to-lead optimization of this series has led to the discovery of the advanced lead compounds possessing the desired fingerprint along with a promising in vivo profile. The lead compounds demonstrated an excellent PK-PD correlation. Administering these agents has significantly reversed scopolamine- and MK801-induced deficit in a rodent novel object recognition paradigm and passive avoidance test. The compounds have also reversed the deficit in water maze spatial learning compared to vehicle-treated scopolamine-matched controls. These studies provide further support for the potential therapeutic utility of 5-HT6 receptor antagonists possessing a desired fingerprint in disorders characterized by cognitive deficits such as Alzheimer's Disease.
The Drosophila fusome, a germline-specific organelle, contains membrane skeletal proteins and functions in cyst formation (1994)

Oogenesis in Drosophila takes place within germline cysts that support polarized transport through ring canals interconnecting their 15 nurse cells and single oocyte. Developing cystocytes are spanned by a large cytoplasmic structure known as the fusome that has been postulated to help form ring canals and determine the pattern of nurse cell-oocyte interconnections. We identified the adducin-like hts product and alpha-spectrin as molecular components of fusomes, discovered a related structure in germline stem cells and documented regular associations between fusomes and cystocyte centrosomes. hts mutations completely eliminated fusomes, causing abnormal cysts containing a reduced number of cells to form. Our results imply that Drosophila fusomes are required for ovarian cyst formation and suggest that membrane skeletal proteins regulate cystocyte divisions.
Intravenous immunoglobulin utilization in the Canadian Atlantic provinces: a report of the Atlantic Collaborative Intravenous Immune Globulin Utilization Working Group (2007)

A regional collaborative strategy for monitoring IVIG use was established. Most of the IVIG use was for labeled or appropriate indications. The majority of unlabeled use was supported by the medical literature. Strategies to optimize IVIG utilization were associated with a decrease in inappropriate IVIG use and a plateau in IVIG utilization compared to the rest of the country.
Familial Alzheimer's disease A pedigree with a mis-sense mutation in the amyloid precursor protein gene (amyloid precursor protein 717 valine → glycine) (1993)

Ten affected individuals are described from a kindred with autosomal dominant familial Alzheimer's disease in which a mutation in the amyloid precursor protein gene results in a valine to glycine substitution at amyloid precursor protein 717 which co-segregates with the disease. The mean age at onset of symptoms was 52 years with a range from 40 years to 67 years. The median duration of the disease was 11 years, with a range of 7-16 years. All individuals fulfilled the National Institute for Neurological and Communicative Disorders and Stroke criteria for probable Alzheimer's disease. A homogeneous clinical and neuropsychological pattern was evident within the family. Myoclonic jerks, seizures, depression and a lack of insight were common features. Positron emission tomography demonstrated biparietal bitemporal hypometabolism in the one affected individual who was studied. The diagnosis was confirmed histopathologically in one individual.
Interdependence of Exchangeable Sodium and Plasma Renin Concentration in Determining Blood Pressure in Patients Treated by Maintenance Dialysis (1973)

Plasma renin concentration and exchangeable sodium were measured in 13 patients with terminal renal failure maintained by dialysis therapy. Blood pressure in seven "responsive" patients was controlled by ultrafiltration but was not controlled in six "resistant" patients. Plasma renin concentration was inversely related to exchangeable sodium in the responsive group but was inappropriately high for the level of exchangeable sodium in the resistant group. There was a better correlation between mean blood pressure and the product of plasma renin concentration and exchangeable sodium than with renin concentration alone.These results indicate that a severely diseased kidney can respond to changes in exchangeable sodium by alterations in renin secretion and they also support the concept that the potential pressor effect of renin is modified by exchangeable sodium. The product of the two factors might be used to determine the "effective" plasma renin concentration in respect of blood pressure.
Nitric oxide synthase inhibitors improve skin flap survival in the rat (1994)

The ability of nitric oxide (NO) synthase inhibitors to reduce ischemia-induced skin flap necrosis was assessed using a modified McFarlane flap in the rat. Flap survival was significantly improved in L-NIO treated (86 +/- 2%), L-NAME-treated (84 +/- 2%), and aminoguanidine-treated (76 +/- 2%) animals compared to the saline-treated group (54 +/- 2%), P < 0.005. Inhibition of NO synthase significantly decreased the hyperemia and edema within the flaps at 24 hours post-elevation. These findings suggest that endogenous NO production contributes to ischemic necrosis and that inhibition of NO synthase may prove useful in extending survival of tissues subjected to ischemia.
mTOR Inhibition (2016)

BACKGROUND: Sirolimus (SRL) has been associated with new-onset diabetes mellitus after transplantation. The aim was to determine the effect of SRL on development of insulin resistance and β-cell toxicity. METHODS: Lean Zucker rat (LZR) and obese Zucker rat (OZR) were distributed into groups: vehicle and SRL (0.25, 0.5, or 1.0 mg/kg) during 12 or 28 days. Intraperitoneal glucose tolerance test (IPGTT) was evaluated at days 0, 12, 28, and 45. Islet morphometry, β-cell proliferation, and apoptosis were analyzed at 12 days. Islets were isolated to analyze insulin content, insulin secretion, and gene expression. RESULTS: After 12 days, SRL treatment only impaired IPGTT in a dose-dependent manner in OZR. Treatment prolongation induced increase of area under the curve of IPGTT in LZR and OZR; however, in contrast to OZR, LZR normalized glucose levels after 2 hours. The SRL reduced pancreas weight and islet proliferation in LZR and OZR as well as insulin content. Insulin secretion was only affected in OZR. Islets from OZR + SRL rats presented a downregulation of Neurod1, Pax4, and Ins2 gene. Genes related with insulin secretion remained unchanged or upregulated. CONCLUSIONS: In conditions that require adaptive β-cell proliferation, SRL might reveal harmful effects by blocking β-cell proliferation, insulin production and secretion. These effects disappeared when removing the therapy.
Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis. (1994)

Glomerular infiltration by neutrophils is a hallmark of acute glomerulonephritis. The pathophysiological role of interleukin 8 (IL-8), a potent neutrophil chemotactic cytokine (chemokine), was explored in an animal model of acute immune complex-mediated glomerulonephritis by administering a neutralizing antibody against IL-8. Repeated injection of bovine serum albumin (BSA) into rabbits caused the deposition of immune complexes consisting of BSA and rabbit IgG in glomeruli. Histological analyses revealed a small but significant number of neutrophils in glomeruli and the fusion of epithelial cell foot processes. Concomitantly, urinary levels of protein and albumin increased markedly (3.20 +/- 0.97 and 1.39 +/- 0.53 mg/h, respectively) compared with those of untreated animals (0.77 +/- 0.21 and 0.01 +/- 0.01 mg/h, respectively). Anti-IL-8 antibody treatment decreased the number of neutrophils in glomeruli by 40% and dramatically prevented the fusion of epithelial cell foot process. Furthermore, treatment with anti-IL-8 antibody completely normalized the urinary levels of protein and albumin (0.89 +/- 0.15 and 0.02 +/- 0.01 mg/h, respectively). These results indicated that IL-8 participated in the impairment of renal functions in experimental acute immune complex-mediated glomerulonephritis through activating as well as recruiting neutrophils.
Kinetic Resolution of Oxiranes by Use of Chiral Lewis Acid Catalysts (1993)

The kinetic resolution of oxiranes by use of chiral Lewis acid catalysts is described. Improved stereoselectivities are observed in the nucleophilic ring opening of oxiranes with secondary amines. For the first time the enantioselective insertion of CO2 into the oxirane ring forming enantiomerically enriched 1,3-dioxolanones was achieved applying chirally modified Zr- and Ti-complexes.