Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. (1/34)

House dust mite (HDM) allergens are important factors in the increasing prevalence of asthma. The lung epithelium forms a barrier that allergens must cross before they can cause sensitization. However, the mechanisms involved are unknown. Here we show that the cysteine proteinase allergen Der p 1 from fecal pellets of the HDM Dermatophagoides pteronyssinus causes disruption of intercellular tight junctions (TJs), which are the principal components of the epithelial paracellular permeability barrier. In confluent airway epithelial cells, Der p 1 led to cleavage of the TJ adhesion protein occludin. Cleavage was attenuated by antipain, but not by inhibitors of serine, aspartic, or matrix metalloproteinases. Putative Der p 1 cleavage sites were found in peptides from an extracellular domain of occludin and in the TJ adhesion protein claudin-1. TJ breakdown nonspecifically increased epithelial permeability, allowing Der p 1 to cross the epithelial barrier. Thus, transepithelial movement of Der p 1 to dendritic antigen-presenting cells via the paracellular pathway may be promoted by the allergen's own proteolytic activity. These results suggest that opening of TJs by environmental proteinases may be the initial step in the development of asthma to a variety of allergens.  (+info)

Assembly and activation of HK-PK complex on endothelial cells results in bradykinin liberation and NO formation. (2/34)

Prekallikrein (PK) activation on human umbilical endothelial cells (HUVEC) presumably leads to bradykinin liberation. On HUVEC, PK activation requires the presence of cell-bound high-molecular-weight kininogen (HK) and Zn(2+). We examined the Zn(2+) requirement for HK binding to and the consequences of PK activation on endothelial cells. Optimal HK binding (14 pmol/10(6) HUVEC) is seen with no added Zn(2+) in HEPES-Tyrode buffer containing gelatin versus 16--32 microM added Zn(2+) in the same buffer containing bovine serum albumin. The affinity and number of HK binding sites on HUVEC are a dissociation constant of 9.6 +/- 1.8 nM and a maximal binding of 1.08 +/- 0.26 x 10(7) sites/cell (means +/- SD). PK is activated to kallikrein by an antipain-sensitive mechanism in the presence of HK and Zn(2+) on HUVEC, human microvascular endothelial cells, umbilical artery smooth muscle cells, and bovine pulmonary artery endothelial cells. Simultaneous with kallikrein formation, bradykinin (5.0 or 10.3 pmol/10(6) HUVEC in the absence or presence of lisinopril, respectively) is liberated from cell-bound HK. Liberated bradykinin stimulates the endothelial cell bradykinin B2 receptor to form nitric oxide. Assembly and activation of PK on endothelial cells modulates their physiological activities.  (+info)

Identification of prolylcarboxypeptidase as the cell matrix-associated prekallikrein activator. (3/34)

Investigations determined that the cell matrix-associated prekallikrein (PK) activator is prolylcarboxypeptidase. PK activation on human umbilical vein endothelial cell (HUVEC) matrix is inhibited by antipain (IC(50)=50 microM) but not anti-factor XIIa antibody, 3 mM benzamidine, 5 mM iodoacetic acid or iodoacetamide, or 3 mM N-ethylmaleimide. Corn trypsin inhibitor (IC(50)=100 nM) or Fmoc-aminoacylpyrrolidine-2-nitrile (IC(50)=100 microM) blocks matrix-associated PK activation. Angiotensin II (IC(50)=100 microM) or bradykinin (IC(50)=3 mM), but not angiotensin 1-7 or bradykinin 1-5, inhibits matrix-associated PK activation. ECV304 cell matrix PK activator also is blocked by 100 microM angiotensin II, 1 microM corn trypsin inhibitor, and 50 microM antipain, but not angiotensin 1-7. 1 mM angiotensin II or 300 microM Fmoc-aminoacylpyrrolidine-2-nitrile indirectly blocks plasminogen activation by inhibiting kallikrein formation for single chain urokinase activation. On immunoblot, prolylcarboxypeptidase antigen is associated with HUVEC matrix. These studies indicate that prolylcarboxypeptidase is the matrix PK activator.  (+info)

Involvement of secreted Aspergillus fumigatus proteases in disruption of the actin fiber cytoskeleton and loss of focal adhesion sites in infected A549 lung pneumocytes. (4/34)

Aspergillus fumigatus is an opportunistic pathogenic fungus that predominantly infects the respiratory system. Penetration of the lung alveolar epithelium is a key step in the infectious process. The cytoskeleton of alveolar epithelial cells forms the cellular basis for the formation of a physical barrier between the cells and their surroundings. This study focused on the distinct effects of A. fumigatus on the actin cytoskeleton of A549 lung pneumocytes. Of the 3 major classes of cytoskeletal fibers--actin microfilaments, microtubules, and intermediate filaments--only the actin cytoskeleton was found to undergo major structural changes in response to infection, including loss of actin stress fibers, formation of actin aggregates, disruption of focal adhesion sites, and cell blebbing. These changes could be specifically blocked in wild-type strains of A. fumigatus by the addition of antipain, a serine and cysteine protease inhibitor, and were not induced by an alkaline serine protease-deficient strain of A. fumigatus. Antipain also reduced, by approximately 50%, fungal-induced A549 cell detachment from the plates and reduction in viability. Our findings suggest that A. fumigatus breaches the alveolar epithelial cell barrier by secreting proteases that act together to disorganize the actin cytoskeleton and destroy cell attachment to the substrate by disrupting focal adhesions.  (+info)

Enzymatic characterization of a cubilin-related serine proteinase from the hard tick Haemaphysalis longicornis. (5/34)

In the present study, we performed enzymatic characterization of Haemaphysalis longicornis serine proteinase (HlSP) with a view to shed light on the mechanisms of blood digestion in the hard ticks. Escherichia coli-expressed recombinant HlSP (rHlSP) was shown to potently hydrolyze the synthetic substrates Bz-(DL)-Arg-pNA, Z-Ala-Ala-Leu-pNA and Suc-Ala-Ala-Ala-pNA and yielded an activity of 31.5, 88.2 and 18.3 mumol/min/mg protein, respectively at an optimum temperature of 25 degrees C. However, the enzyme showed little activity to hydrolyze the substrates Suc-Arg-Pro-Phe-His-Leu-Leu-Val-Tyr-MCA and Pyr-Phe-Leu-pNA. The optimum pH for the enzyme was shown to be 4.0 to 5.0. Several inhibitors such as antipain, leupeptin and phenylmethylsulfonyl fluoride (PMSF), specific for serine proteinase were shown to inhibit enzyme activity by 20-82%, while E-64 (specific for cysteine proteinases) and pepstatinA (specific for aspartic proteinases) had shown only little inhibitory effects on it. This is the first report on enzymatic characterization of a functional serine proteinase from the hard ticks.  (+info)

Light-induced D1 protein degradation is catalyzed by a serine-type protease. (6/34)

Light-induced degradation of the D1 protein in isolated spinach photosystem II core preparations was studied after addition of various protease inhibitors. The degradation was selectively inhibited by several serine protease inhibitors in particular diisopropylfluorophosphate. The results demonstrate that the D1 protein is degraded by a serine-type of proteolytic activity that is an integral part of photosystem II.  (+info)

Antipain-induced suppression of oncogene expression in H-ras-transformed NIH3T3 cells. (7/34)

Antipain (AP; 50 micrograms/ml) inhibits transformation of NIH3T3 cells after transfection with an activated H-ras oncogene. To determine whether AP effects on transformation are associated with alterations in oncogene expression, NIH3T3 cells were cotransfected with an activated H-ras oncogene and the selectable marker gene aph, and gene expression was quantified. Fifty percent of geneticin-resistant colonies which were exposed to AP failed to express the transformed phenotype as determined by their inability to grow in soft agar. Northern blot analysis of the transformed and nontransformed colonies revealed that suppression of H-ras transformation by AP was associated with a decrease in expression of the exogenously transfected H-ras gene by approximately 4-fold. Expression of the endogenous oncogene c-myc was decreased by approximately 2.5-fold, to levels seen in untransfected cells. AP-treated colonies that retained the transformed phenotype had levels of oncogene expression that were similar to untreated ras-transformed colonies. Southern blot analysis revealed no effects of AP on incorporation or copy number of the H-ras gene.  (+info)

Repression of serotonin secretion by an endogenous Ca2(+)-activated protease in electropermeabilized bovine platelets. (8/34)

Micromolar levels of free calcium ions added to the extracellular medium elicit secretion of serotonin from electropermeabilized bovine platelets in the presence of millimolar levels of Mg-ATP. Such Ca2(+)-dependent secretion of serotonin was almost completely impaired when the permeabilized platelets were preincubated for 1 min at 35 degrees C in 100 microM Ca2+ without Mg-ATP. The half-maximal effect was observed with about 45 microM Ca2+ in the preincubation medium. Inhibitors of serine-thiol protease, such as leupeptin and antipain, suppressed the impairment of the secretion of serotonin by the preincubation with Ca2+. Electron microscopic observation revealed that disorganization of the cytoskeletal structures, in particular of the membrane undercoat and the network of microfilaments, accompanied the impairment of secretion of serotonin. Microfilaments were also found to be dissociated from dense granules that contained serotonin. These morphological changes were also suppressed when antipain was included in the Ca2(+)-preincubation medium. Coincident with these morphological changes, the following biochemical changes were observed in 100 microM Ca2+ but not in the presence of Ca2+ and antipain. The amount of Triton-insoluble cytoskeleton and the acto-myosin content of the dense-granule fraction were markedly decreased. The decrease in Triton-insoluble cytoskeletons was quantitatively correlated with the degree of impairment of secretion of serotonin. Immunoblot analysis of EGTA extracts of the cells showed that the 240-kDa spectrin in platelets was degraded to a 235-kDa fragment, and a 260-kDa actin-binding protein (ABP) in platelets was partially degraded to 190- and 110-kDa components.(ABSTRACT TRUNCATED AT 250 WORDS)  (+info)

*Antipain

... is an oligopeptide isolated from actinomycetes and used in biochemical research as a protease inhibitor, reported in ... Umezawa, S; Tatsuta, K; Fujimoto, K; Tsuchiya, T; Umezawa, H (1972). "Structure of antipain, a new Sakaguchi-positive product ... Suda, H; Aoyagi, T; Hamada, M; Takeuchi, T; Umezawa, H (1972). "Antipain, a new protease inhibitor isolated from actinomycetes ... In both cases the backbone carbonyl of the terminal arginine of antipain forms a covalent bond to the active site serine in the ...

*Streptomyces michiganensis

... produces actinomycin X, antipain and mitomycin. Xue, Jinghua; Wu, Min (27 March 2015). "Cyclic ...

*William Thomas Rawleigh

... anti-pain) Oil. All of these products were manufactured by Rawleigh and sold from farmhouse to farmhouse in a buggy drawn by a ...

*Oligopeptide

Antipain - An oligopeptide produced by various bacteria which acts as a protease inhibitor. Ceruletide - A specific decapeptide ...

*Clinical neurochemistry

... antipain) medications. Sensitization, in the clinical sense of the word, is a phenomenon in which nociceptors in an area beyond ...

*Protriptyline

A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the ...

*Flurbiprofen

Antipain, Baenazin, Benactiv, Biprofin, Biprotec, Bro-Z, Brufen, Brufoz, Cebutid, Clinadol, Coryfin, Dispain, Edolfene, Eyeflur ...

*Jerry Baker (author)

2003 ISBN 0922433437 Jerry Baker's Anti-Pain Plan, 2004 ISBN 0922433496 Jerry Baker's Backyard Problem Solver, 2004 ISBN ...

*List of MeSH codes (D12.644)

... antipain MeSH D12.644.456.193 --- bradykinin MeSH D12.644.456.193.400 --- kallidin MeSH D12.644.456.241 --- caerulein MeSH ...
Evidence-Based Complementary and Alternative Medicine (eCAM) is an international peer-reviewed, Open Access journal that seeks to understand the sources and to encourage rigorous research in this new, yet ancient world of complementary and alternative medicine.
Product Name: AntipainDescription: Abbr: Alias: Source: Appearance: Pale yellow powderCAS NO: 1345808-25-4 Arginase inhibitor 1 Molecular Weight: 677.2Purity:
Protease Inhibitor A, PIA 100x [PIA100X] - A custom concentration cocktail of two inhibitors in EDTA which has been optimized for the inhibition of calcium-dependent endopeptidases, trypsin-like serine proteases, papain and cysteine proteases. Each vial contains 0.02 mg/ml antipain, 0.05 mg/ml leupeptin, and 50 mg/ml EDTA in water. Supplied with an informational insert.
The field-induced desorption phenomenon [1] of surface atoms or adsorbed molecules gives direct information about the microscopic states of surface atoms. Recently qualitatively different behaviors...
The emission spectra of H2S+ and D2S+ occurring in the region 400 to 500 nm have been analysed in detail. In the lower 2B1 state both molecules are near oblate asymmetric tops, and from the rotational constants an SH(SD) bond length of 0.1358 nm and an HSH(DSD) angle of 92.9° are obtained. In the 2A1 upper state of both molecules the equilibrium angle is about 127° and the SH(SD) bond length is 0.1369 nm. The barrier to linearity in the excited state is ca. 4400 cm-1 and transitions have been observed from levels both below and above the barrier. The two combining states are shown to be derived from an electronic II state which is split by static Renner interaction. The complicated ro-vibronic structure of the excited state is interpreted in terms of a model in which both the dynamic Renner effect and spin-orbit interaction are included. The 2A1 state of H2S+ is shown to play an intermediate role between the analogous high-barrier molecules such as AsH2 (H ca. 9000 cm-1), and the low barrier ...
This is also a pet peeve, as it applies to math and science education. When I start a new project, the first thing I have to do is read the existing literature. This requires a HUGE base of knowledge. Our junior and senior chemistry majors are just about able to do this, with support. High school kids arent, typically. Anecdotal evidence of students engaging with the literature almost always involves highly motivated and very bright students being given a selected problem in a field that has a relatively low barrier to entry. The case Im thinking of is a Princeton freshman seminar, where students who chose to be in that particular seminar dealt with articles in developmental biology, carefully chosen to contain as little biochemistry as possible. Im sure that worked great, but it hardly means that all high school kids should be doing that, rather than developing a framework in biology, chemistry, or whatever! ...
The invention is directed to 1-nitroacridine derivative(s)/tumor inhibitor(s) compositions as well as methods for using said compositions for inhibiting or preventing tumor growth, particularly, prostate cancer cell growth and metastases.
RESULTS: COL6A3 was highly expressed in tissues and cells of bladder cancer. COL6A3 silencing could inhibit the cell proliferation and angiopoiesis. In addition, COL6A3 silencing obviously suppressed the levels of matrix metalloproteinase-2 (MMP2), Matrix metalloproteinase-9 (MMP9), and vimentin. On the contrary, the levels of epithelium-specific cell-cell adhesion molecule (E-cadherin) and tumor inhibitor of metalloproteinase-1 (TIMP-1) were significantly increased. Furthermore, we found that COL6A3 silencing reduced the activity of p-Smad2, p-Smad3, and transforming growth factor β (TGF-β ...
Gold(III)-catalyzed cycloisomerization of α-bis(indol-3-yl)methyl alkynols selectively affords 1-(indol-3-yl)carbazoles, in a transformation that takes place through a selective 1,2-alkyl vs 1,2-vinyl migration step in the vinyl-gold intermediate generated from the initial 5-endo-spirocyclization. The reaction proceeds well with either tertiary or secondary starting alkynols as well as with a wide variety of alkyne substituents. The key role of the other indol-3-yl substituent for the unexpected selectivity in the 1,2 rearrangement has also been supported by DFT calculations that reveal a low barrier, two-step mechanism in the alkyl migration path where the second indole significantly stabilizes a carbocationic intermediate ...
Im just going to throw this out there: I LOVE the Block system and Onell Designs approach to vinyl toys. For a while now, vinyl toys, especially of the designer variety, have had an air or stigma around them based on the intention of the form, and debates about customization and artists intent. Onell has bypassed the issue entirely, and is using vinyl to make affordable large scale companion pieces to their figure line with the same potential for building and customization with a relatively low barrier to entry as the PVC figures. With the advent of the Block system, the potential for Glyos vehicles, mechs, spaceships, and whatever else people think up has exploded. The parts are cheap, available individually, and designed to allow for as much or as little tinkering as you can stand. Once youve come up with something, you are left with a big, chunky, durable vinyl toy of your own design. With a common set of parts, everyone can have a different experience, and I love that.. ...
One of the points I made earlier in this paper is that publishing (like any successful market) is an ecology, in which players feed each other in a complex web of relationships. As an industry matures, you see two countervailing trends: one is towards differentiation, as certain players specialize in one layer of the business or another; at the same time, there is increasing consolidation, as certain players take a lead in a particular layer. Right now, everyone is trying to do it all on the net: provide software, connectivity, content, transaction support, data warehousing, you name it. As the Internet matures, I expect to see a lot of the same kind of specialization occurring as we have in print. Well come to recognize that the roles of author, publisher, manufacturer, distributor and retailer need not be rolled up into the same package. (As an aside, part of what created the low barrier to entry for OReilly & Associates in print publishing was the existence of a lot of infrastructure that ...
Low Barrier Silicon Schottky Diodes: MACOMs MSS30,000 Series of Schottky diodes are fabricated on N-Type epitaxial substrates using proprietary processes that yield the highest FCOs in the industry. Optimum mixer performance is obtained with LO power of -3 dBm to +3 dBm per diode.
Why is it necessary to enjoy such a lewd piece of trash? Perhaps because, like certain trashy material, there is much to be explored beneath the flat surface of the animation. Biting fingers of the MPAA board and savoring the wounds, "South Park" challenges the very stability of the associations film rating system (which, as you may recall, broke an all-time low barrier this summer when it tried to label taunting sexual acts in "Eyes Wide Shut" with an NC-17, and gratuitous bloodcurdling violence in something like "8MM" with a simple R rating). In addition, the movie offers an arrogant slice of evidence in a case built against those who believe media and cinema violence are being intimidated by teenagers who carry guns into schools. No one can take this stuff that seriously; the movie goes so far and pushes so many buttons that, even in the most obvious coincidences, not one single image can be blamed for the decisions made by humans. Life does not intimidate art, and here is a movie that ...
The great thing about walking is it has a low barrier to entry: All it takes is a pair of sneakers and some determination to get going. Not only can incorporating it into your regular routine help boost mood levels, but researchers also found moderate-intensity walking showed a similarly visible reduction in risk for h
The majority of individuals who commence treatment for HIV in the UK start with a regimen that includes EFV in combination with other antiretrovirals. These regimens are convenient (once daily dosing) and highly efficacious. However EFV has several potential drawbacks including continued CNS toxicity, the potential for teratogenesis and a low barrier to the development of virological resistance.. Clinically controlled trials frequently reported undesirable nervous system side effects in patients receiving 600 mg EFV with other antiretroviral agents, including dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming. CNS symptoms of moderate to severe intensity were experienced by 19.4% of patients compared to 9.0% of patients receiving control regimens. These symptoms were severe in 2.0% of patients receiving EFV 600 mg daily and in 1.3% of patients receiving control regimens. In clinical studies 2.1% of patients treated with 600 mg of EFV discontinued therapy because of ...
The majority of individuals who commence treatment for HIV in the UK start with a regimen that includes EFV in combination with other antiretrovirals. These regimens are convenient (once daily dosing) and highly efficacious. However EFV has several potential drawbacks including continued CNS toxicity, the potential for teratogenesis and a low barrier to the development of virological resistance.. Clinically controlled trials frequently reported undesirable nervous system side effects in patients receiving 600 mg EFV with other antiretroviral agents, including dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming. CNS symptoms of moderate to severe intensity were experienced by 19.4% of patients compared to 9.0% of patients receiving control regimens. These symptoms were severe in 2.0% of patients receiving EFV 600 mg daily and in 1.3% of patients receiving control regimens. In clinical studies 2.1% of patients treated with 600 mg of EFV discontinued therapy because of ...
Part I. Field desorption (FD) mass spectra have been obtained from a series of alkali metal cryptates formed from {2.2.2}-, {2.2.1}- and {2.1.1}-cryptands with Li(+), Na(+) and K(+) salts of Cl(-), Br(-), I(-), OTs(-) and BPh(,4)(-). Stabilities of these complexes under FD conditions are compared with their thermodynamic stabilities in solution. Differences in these stabilities are attributed to the lack of solvation of ions under FD conditions. A marked anion effect is also observed in FD spectra. This effect is correlated with the recombination energy of the released cation and anion in the gaseous state. Part II. Acid phthalates from isomeric alicyclic alcohols have been studied by field desorption (FD) and electron impact (EI) mass spectrometry. Isomeric acid phthalates gave identical FD spectra and EI spectra. The use of these methods for distinguishing stereoisomers of this type thus proved to be unsuccessful. However, the field ionization (FI) spectra of cis- and trans-4-t-butylcyclohexyl
The five 7-member rings warp the structure so that it is non-planar. In fact the molecule has negative curvature, reminiscent of a riding saddle. They report the x-ray structure, outside of the fullerenes, the largest hydrocarbon reported by x-ray crystallography. Because of its non-planar geometry, 1 does not pack well and so it is soluble in a variety of solvents.. The authors have obtained the structure of 1 at B3LYP/6-31G(d), shown in Figure 1. The central corranulene component is a shallow bowl, much less shallow than in corranulene itself. This suggests that the compound might flip with a relatively low barrier. The computed barrier is only 1.7 kcal mol-1. Due to the negative curvatures associated with the seven-member rings, 1 is chiral and the ring flipping process leaves the chirality unchanged. A second transition was located that leads to racemization through a transition state of Cs symmetry. The barrier for this racemization is computed to be 18.9 kcal mol-1. Variable temperature 1H ...
A membrane protease possessing thrombin-like activity was purified to homogeneity from mitochondria of rat submaxillary gland. The molecular mass of the enzyme was determined to be 45 kDa by SDS/PAGE under reducing conditions and by gel filtration on a Sephadex G-100 column. The enzyme is a glycoprotein and has an isoelectric point of 3.25. Maximum activity was observed at pH 10.5. Inhibition by di-isopropyl fluorophosphate, benzamidine, aprotinin and antipain suggested the enzyme to be a serine protease. Other inhibitors such as EDTA, soya-bean trypsin inhibitor, lima-bean trypsin inhibitor, TosLysCH2Cl and chymostatin did not alter the activity. The enzyme showed affinity towards different synthetic substrates (p-nitroanilide derivatives) containing arginine at the P1 position. Kinetic studies revealed that kcat./Km was highest with the substrate N-Bz-Phe-Val-Arg-p-nitroanilide. The enzyme exhibits significant plasma-coagulating activity. The coagulation initiated by the enzyme was not altered ...
Hartree-Fock, Moller-Plesset, and density functional theory calculations have been carried out using 6-31+G(d), 6-31+G(d,p) and 6-31++G(d,p) basis sets to study the properties of low-barrier or short-strong hydrogen bonds (SSHB) and their potential role in enzyme-catalyzed reactions that involve proton abstraction from a weak carbon-acid by a weak base. Formic acid/formate anion, enol/enolate and other complexes have been chosen to simulate a SSHB system. These complexes have been calculated to form very short, very short hydrogen bonds with a very low barrier for proton transfer from the donor to the acceptor. Two important environmental factors including small amount of solvent molecules that could possibly exist at the active site of an enzyme and the polarity around the active site were simulated to study their energetic and geometrical influences to a SSHB. It was found that microsolvation that improves the matching of pK as of the hydrogen bond donor and acceptor involved in the SSHB will ...
What do these societies have in common: Gotham City before Batman, the Star Wars universe under Emperor Palpatine, the wizarding world of Harry Potter, and the United States under George W. Bush? The citizens of these societies experienced learned helplessness. Whats learned helplessness? It is the type of "giving up" that happens to people when they are repeatedly or chronically in an aversive situation and nothing they do can stop or help them escape from it. The original research on learned helplessness, by psychologists Bruce Overmeier and Martin Seligman, went like this: A dog was placed in a cage, and received shocks from which it could not escape. After an initial response of agitation and making noises, the dog eventually became passive in response to the shocks-as if it gave up. The dog was then put in a new cage-with two halves that had a low barrier between the halves. If the dog jumped over the barrier when shocked, it could escape the shock. But the dog never did go over the ...
What do these societies have in common: Gotham City before Batman, the Star Wars universe under Emperor Palpatine, the wizarding world of Harry Potter, and the United States under George W. Bush? The citizens of these societies experienced learned helplessness. Whats learned helplessness? It is the type of "giving up" that happens to people when they are repeatedly or chronically in an aversive situation and nothing they do can stop or help them escape from it. The original research on learned helplessness, by psychologists Bruce Overmeier and Martin Seligman, went like this: A dog was placed in a cage, and received shocks from which it could not escape. After an initial response of agitation and making noises, the dog eventually became passive in response to the shocks-as if it gave up. The dog was then put in a new cage-with two halves that had a low barrier between the halves. If the dog jumped over the barrier when shocked, it could escape the shock. But the dog never did go over the ...
Two conformers, cis-cis and trans-perp HOONO, are identified in the 2vOH region by vibrational overtone initiated photodissociation spectroscopy, and the isomerization barrier from the less stable trans-perp to cis-cis HOONO is determined experimentally, statistically, and ab initio to be ~ 40 kJ/mol. This low barrier indicates that only cis-cis HOONO is atmospherically important. The complex vibrational spectroscopy of cis-cis HOONO is assigned with the aid of a simple two-dimensional OH-stretch/torsion coupling model of the planar, partially hydrogen-bound molecule. Combined with nonuniform quantum yield, this model explains the major features in the cis-cis HOONO spectrum. Its application to the fundamental region suggests an upward adjustment of the atmospherically important HOONO/HONO2 product branching ratio in the OH + NO2 association reaction. The rotational spectrum and dipole moment of cis-cis HOONO and DOONO are measured in the submillimeter region to characterize the molecular ...
Todays post focuses on another question from a reader, who asked: "How will we decide which therapies to give patients with metastatic melanoma once the new immunotherapies are available?". This is not an easy question to answer, but first lets remember that as little as five years ago there were only treatments such as DTIC (dacarbazine), temozolamide, interferon, chemotherapy and not much else as choices for people with advanced melanoma. Survival rates were generally poor, yet despite the low barrier to entry, many agents failed miserably to beat them. The disease was therefore widely considered to be a graveyard for Pharma R&D.. Fast forward to 2014. We now have several targeted therapies and combinations approved including BRAFV600E (vemurafenib and dabrafenib) and MEK inhibitors (trametinib), as well as a number of others that may soon be on the way in the near term such as cobimetinib in combination with vemurafenib. Along similar lines, GSK recently announced that the combination of ...
Because the landscaping profession has a generally low barrier of entry, homeowners need to be particularly vigilant in checking references and finding out about a companys track record. Mary Ellen Burton says be wary of so-called pickup truck landscapers. These nefarious gardeners will affix magnetic signs to their trucks as identification rather than using the more permanent painted-on logos. But their inexperience can do lasting damage. Burton says these landscapers will commit such mistakes as applying too little mulch to soil or planting a tree too deeply. She has even seen landscaped homes with Leyland cypress planted near the front door -- a major foliage faux pas. "Typically, Leylands are used as a screening plant," says Burton, but if you plant one too close to the house, "in two years it will grow to be as tall as your entryway." To avoid such foul-ups, make sure the landscaper has liability insurance (about $1 million is a reasonable amount of coverage), and vet him through the ...
Two Chinese hamster ovary (CHO) cell variants differ substantially in their sensitivity to N-methyl-N -nitro-N-nitrosoguanidine (MNNG). The resistant clone (Cl 3) was isolated from the sensitive...
Introduction When implantation of the fertilized ovum occurs anywhere outside of the uterine cavity it is called ectopic pregnancy. Abdominal pregnancy is a rare type of ectopic pregnancy where the developing embryo implants and grows within the peritoneal cavity. Abdominal pregnancy is classified as being primary and secondary. Most abdominal (ectopic) pregnancies are secondary from aborted or ruptured tubal pregnancy. Extrauterine abdominal pregnancy is missed during antenatal period even with the use of ultrasound. Case history A 39 years old woman gravida VI, para V with history of severe supra pubic pain at 10 weeks of amenorrhea which was treated with Antipain and bed rest presented to the maternity hospital. During ante natal follow up abnormal fetal malpresentation and easily fetal parts were palpated. Diagnosis was missed during ante natal period. The eminent signs were clients history and flat abdomen x-ray which revealed the fetal demise. At first client was managed conservatively ...
2017 RTI International. RTI is a registered trademark and trade name of Research Triangle Institute. The RTI logo is a registered trademark of Research Triangle Institute. ...
Effect of DTT on prolyl oligopeptidase levels in plasma from healthy and RR-MS patients. POP activity in plasma from healthy controls (white bar) and RR-MS pati
Rat R2k rhabdomyosarcoma cells were transfected with the human H-ras oncogene, which resulted in increased resistance to cell kill in vitro by a single dose of 137Cs γ-rays. A subline carrying one oncogene showed an increase in the quasi-threshold dose (D(q)) from 0.88 to 1.48 Gy. Another subline containing six oncogenes not only had an increased D(q) of 1.59 Gy but also showed an increase in the dose reducing cell survival to a fraction of e-1 = 0.37 (D0) from 1.25 to 1.76 Gy. Analysis of the cell survival data according to the linear-quadratic formalism indicated that a decrease in the value of the coefficient of the linear component α is associated with a H-ras-mediated increase in radioresistance. In fractionated irradiation experiments it was observed that with a dose of 1 Gy/fraction a 1.8 times higher dose for an isoeffect of 10% cell survival (D10) was needed for a subline with one H-ras oncogene, while with fraction doses of 2 or 4 Gy only a 1.2 times higher D10 was found. This ...
1H2X: Electrostatic Effects and Binding Determinants in the Catalysis of Prolyl Oligopeptidase: Site Specific Mutagenesis at the Oxyanion Binding Site
Mast cell activation in vivo is often associated with areas of oedema and connective-tissue degradation. Tryptase and chymase are the major serine proteinases released by mast cells, but they appear to have little activity on most components of the extracellular matrix. The matrix metalloproteinases (MMP) are purported to degrade almost all connective tissue elements and are secreted by cells in the form of inactive precursors. Since the mechanisms of MMP activation in vivo are poorly understood we have examined the potential of mast cell proteinases to activate the precursor forms of human collagenase (MMP-1), stromelysin (MMP-3), gelatinase A (MMP-2) and gelatinase B (MMP-9).. Mast cell proteinases prepared from purified dog mastocytoma cells were shown to process and activate purified precursor forms of both MMP-1 and MMP-3. Using antipain and chymostatin, inhibitors for tryptase and chymase, respectively, it was demonstrated that both pMMP-1 and pMMP-3 were effectively processed and ...
Aerolysin is a major virulence factor produced by the Gram-negative bacterium Aeromonas hydrophila and is a member of the beta-pore-forming toxin family. Two oligomerization-deficient aerolysin mutants, H132D and H132N, have been overproduced, proteolyzed by trypsin digestion and purified. Crystals were grown from the proteolyzed forms and diffraction data were collected for the two mutants to 2.1 and 2.3 A resolution, respectively. The prism-shaped crystals belonged to space group C2. The crystal structure of the mutants in the mature, but not heptameric, aerolysin form will provide insight into the intermediate states in the oligomerization process of a pore-forming toxin.. Keywords: aerolysin ; virulence factors ; Aeromonas hydrophila ; Site-Directed Mutagenesis ; Septicum Alpha-Toxin ; Channel Formation ; Membrane-Channel ; Activation ; Binding ; Complex ; Crystallization ; Proaerolysin ; Diffraction. ...
The prolyl oligopeptidase family, which is a group of serine peptidases, can hydrolyze peptides smaller than 30 residues. The prolyl oligopeptidase family in plants includes four members, which are prolyl oligopeptidase (POP, EC3.4.21.26), dipeptidyl peptidase IV (DPPIV, EC3.4.14.5), oligopeptidase B (OPB, EC3.4.21.83), and acylaminoacyl peptidase (ACPH, EC3.4.19.1). POP is found in human and rat, and plays important roles in multiple biological processes, such as protein secretion, maturation and degradation of peptide hormones, and neuropathies, signal transduction and memory and learning. However, the function of POP is unclear in plants. In order to study POP function in plants, we cloned the cDNA of the OsPOP5 gene from rice by nested-PCR. Sequence analysis showed that the cDNA encodes a protein of 596 amino acid residues with Mw ≈ 67.29 kD. In order to analyze the protein function under different abiotic stresses, OsPOP5 was expressed in Escherichia coli. OsPOP5 protein enhanced the
1H2X: Electrostatic Effects and Binding Determinants in the Catalysis of Prolyl Oligopeptidase: Site Specific Mutagenesis at the Oxyanion Binding Site
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One objective of the red-white muscle experiment was simply to test the function of the newly assembled porcine microarray, from which two gene lists were generated (Tables 1 and 2). Genes that were expected to be differentially expressed and genes that were novel were found on each list. The microarray results validated our prior hypothesis of differential gene expression in red and white muscles, thus demonstrating the functional integrity of our newly constructed microarray. One of the well established distinguishing features of red muscle is its relatively high oxidative phosphorylation capacity, reflected by an abundance of mitochondria in red muscles. It is reassuring that genes from the mitochondrial genome were well represented in the red muscle pool of differentially expressed genes (Table 1). White muscles comprise predominantly more fast-glycolytic fibres than red muscles. Our findings were consistent with expectations, in that most of the 45 clones selected as more highly expressed ...
Using low energy electron (LEE) as a catalyst, the electronic origin of the catalytic strategies corresponding to substrate selectivity, reaction specificity and reaction rate enhancement are investigated for a reversible unimolecular elementary reaction. An electronic energy complementarity between the catalyst and the substrate molecule is the origin of substrate selectivity and reaction specificity. The electronic energy complementarity is induced by tuning the electronic energy of the catalyst. The energy complementarity maximizes the binding forces between the catalyst and the molecule. Consequently, a new electronically metastable high-energy reactant state and a corresponding new low barrier reaction path are resonantly created for a specific reaction of the substrate through the formation of a catalyst-substrate transient adduct. The LEE catalysis also reveals a fundamental \textit{structure-energy correspondence} in the formation of the catalyst-substrate transient adduct. Since the ...
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author ...
Bovine platelet plasmin inhibitor (BPPI) is a novel Kunitz inhibitor, recently discovered in platelets (Li, 1992) for which an expression system is sought. Because the proteins origin of synthesis was unknown, a search for a genomic clone was undertaken. PCR was used in an attempt to amplify the BPPI gene from lymphocyte, bovine genomic DNA. The first set of primers used was designed according to the N and C termini of the amino acid sequence of BPPI (P1/P2). These were based on a degenerate nucleotide sequence derived from its amino acid sequence. Amplification with this set of primers was unsuccessful. The second approach in amplifying the gene was to increase the specificity of the primers in the 3 end (P3/P4) using a table of codon usage of the bovine genome. Two successive amplifications led to the formation of a 230 bp fragment. The sequence of this product was not comparable to the degenerate sequence of BPPI. A third set of primers (P6/P7) was designed according to the gene sequence of SI (II)
Definition of Haemaphysalis cinnabarina with photos and pictures, translations, sample usage, and additional links for more information.
Imagine if we started recognizing trauma, pain, grief, and fear without defensiveness or denial. What would a society like that look like?
PURPOSE Antibody-drug conjugates (ADC) selectively deliver a cytotoxic drug to cells expressing an accessible antigenic target. Here, we have appended monomethyl auristatin E (MMAE) to an antibody recognizing the SLC34A2 gene product NaPi2b, the type II sodium-phosphate cotransporter, which is highly expressed on tumor surfaces of the lung, ovary, and thyroid as well as on normal lung pneumocytes. This study evaluated its efficacy and safety in preclinical studies. EXPERIMENTAL DESIGN The efficacy of anti-NaPi2b ADC was evaluated in mouse ovarian and non-small cell lung cancer (NSCLC) tumor xenograft models, and its toxicity was assessed in rats and cynomolgus monkeys. RESULTS We show here that an anti-NaPi2b ADC is effective in mouse ovarian and NSCLC tumor xenograft models and well-tolerated in rats and cynomolgus monkeys at levels in excess of therapeutic doses. Despite high levels of expression in normal lung of non-human primate, the cross-reactive ADC exhibited an acceptable safety profile
Definition of Clostridium septicum. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms and definitions.
Vimentin, desmin, glial fibrillary acidic protein, neurofilament triplet proteins, and a mixture of cytokeratins were digested with Ca2+-activated neutral thiol proteinase isolated from Ehrlich ascites tumor (EAT) cells and porcine kidney. All intermediate filament proteins were degraded by the proteinase, although with different rates and Ca2+ optima. These results are in part at variance with our previous statement that the Ca2+-activated proteinase from EAT cells is specific for vimentin and desmin.. ...
Mass spectrometry has been an important part of nearly all of my approximately 180 publications. In the earliest stage of my research career (years 1965-1975), I designed and constructed specialized mass spectrometers for studies of gas phase ion-molecule reactions. Drs. Jean Futrell and Marvin Vestal, two widely recognized leaders in the field of mass spectrometry fundamentals, were mentors during this period. In the next stage of my research career (years 1976-1984), my interest shifted to applications of mass spectrometry to identify modified forms of nucleic acids. During this time, I developed high sensitivity methods for exact mass measurements, chemical derivatization, advanced instrumentation for field desorption ionization, and GC MS interfaces optimized for highly polar compounds. Dr. James McCloskey, the leader in this area, was my mentor.. In 1984, I took my first tenure-track position (Purdue University) where I developed several research programs based on applications of mass ...
Thank you for your interest in spreading the word about Biochemical Society Transactions.. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.. ...

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