17,498 research outputs found
Drug Effect Unveils Inter-head Cooperativity and Strain-dependent ADP Release in Fast Skeletal Actomyosin
No full textAmrinone is a bipyridine compound with characteristic effects on the force-velocity relationship of fast skeletal muscle, including a reduction in the maximum shortening velocity and increased maximum isometric force. Here we performed experiments to elucidate the molecular mechanisms for these effects, with the additional aim to gain insight into the molecular mechanisms underlying the force-velocity relationship. In vitro motility assays established that amrinone reduces the sliding velocity of heavy meromyosin-propelled actin filaments by 30% at different ionic strengths of the assay solution. Stopped-flow studies of myofibrils, heavy meromyosin and myosin subfragment 1, showed that the effects on sliding speed were not because of a reduced rate of ATP-induced actomyosin dissociation because the rate of this process was increased by amrinone. Moreover, optical tweezers studies could not detect any amrinone-induced changes in the working stroke length. In contrast, the ADP affinity of acto-heavy meromyosin was increased about 2-fold by 1 mm amrinone. Similar effects were not observed for acto-subfragment 1. Together with the other findings, this suggests that the amrinone-induced reduction in sliding velocity is attributed to inhibition of a strain-dependent ADP release step. Modeling results show that such an effect may account for the amrinone-induced changes of the force-velocity relationship. The data emphasize the importance of the rate of a strain-dependent ADP release step in influencing the maximum sliding velocity in fast skeletal muscle. The data also lead us to discuss the possible importance of cooperative interactions between the two myosin heads in muscle contraction
Work stress, smoking status and smoking intensity: an observational study of 46 190 employees
No full textStudy objective: To examine the relationship between work stress, as indicated by the job strain model and the effort-reward imbalance model, and smoking.
Setting: Ten municipalities and 21 hospitals in Finland.
Design and Participants: Binary logistic regression models for the prevalence of smoking were related to survey responses of 37 309 female and 8881 male Finnish public sector employees aged 17-65. Separate multinomial logistic regression models were calculated for smoking intensity for 8130 smokers. In addition, binary logistic regression models for ex-smoking were fitted among 16 277 former and current smokers. In all analyses, adjustments were made for age, basic education, occupational status, type of employment and marital status.
Main results: Respondents with high effort-reward imbalance or lower rewards were more likely to be smokers. Among smokers, an increased likelihood of higher intensity of smoking was associated with higher job strain and higher effort-reward imbalance and their components such as low job control and low rewards. Smoking intensity was also higher in active jobs in women, in passive jobs and among employees with low effort expenditure. Among former and current smokers, high job strain, high effort-reward imbalance and high job demands were associated with a higher likelihood of being a current smoker. Lower effort was associated with a higher likelihood of ex-smoking.
Conclusions: This evidence suggests an association between work stress and smoking and implies that smoking cessation programs may benefit from the taking into account the modification of stressful features of work environment.
Key words: effort-reward imbalance; job strain; smoking.
Abbreviations: OR, odds ratio; CI, confidence interval; SES, socioeconomic statu
Isolation of TNT tolerant pseudomonas species (Strain KA) from TNT contaminated soil biotransformation of TNT
No full text"A 2,4,6-trinitrotoluene (TNT) utilising bacterium, Pseudomonas species (strain KA) was isolated from soils of a munitions processing unit and studied for itsability to grow and metabolise TNT. The result indicated that the isolate could grow aerobically in a minimal salt medium containing 0.25 mM/l TNT at 30 °C. It could completely transform 0.25 mM/l TNT in 5 days giving 2-isomeric monoaminodinitrotoluenes, namely 4-aminodinitrotoluene and 2-aminodinitrotoluene. Products of TNT transformation were analysed and confirmed by thin layer chromatography and gas chromatography coupled with mass spectrometry. Both, growth of the isolate and biotransformation rates were better supported on sugar and ammonium salt when added to the medium separately. Pseudomonas species (strain KA) showed maximum TNT transformation efficiency in the presence of mannose. For degradation of TNT, this strain can be employed to initiate the process in association with the other microbial members that can collectively degrade TNT
Una interpretación de a-ka-na-jo ( a3-ka-na-jo)
No full textThe author studies the word a-ka-na-jo in the PY Cn 328 tablet and taking into account some factors she proposes αγναιος as the reading of this word.The author studies the word a-ka-na-jo in the PY Cn 328 tablet and taking into account some factors she proposes αγναιος as the reading of this word
Environmental influences over the last 16 ka on compound-specific δ13C variations of leaf wax n-alkanes in the Hani peat deposit from northeast China
No full textCompound-specific carbon isotope ratios (δ13C) of leaf wax n-alkanes (C21-C33 odd carbon numbered n-alkanes) were measured in the Hani peat sequence from northeast China. These data were compared with lipid biomarker compositions to assess changes in local vegetation and paleoclimate for the last 16 ka The δ13C values of n-alkanes range between -36.6 and -30.7‰, showing that the compounds originate from C3 plants. Much larger variations (∼5.4‰) in the n-alkane δ13C values than those of atmospheric CO2 during the last 16 ka (< 0.5‰) indicate that the isotopic values were affected by environmental factors in addition to the postglacial δ13C variations in the atmospheric reservoir. The stratigraphic records of δ13C reveal decoupled fluctuations among the individual n-alkanes, particularly between 15.5 to 11.4 ka. Synchronous excursions in the δ13C offsets among individual n-alkanes (Δδ13C) and lipid biomarker paleoplant proxies (Paq, and C23/C31 and C27/C31) from 14.9 to 13.2 ka and 12.7 to 11.6 ka suggest that vegetational changes are the most likely causes for the decoupled δ13C variations. Parallel fluctuations of the δ13C values of terrestrial higher plant-derived C29 and C31 n-alkanes and the n-alkane average chain-length (ACL) from 11 to 6 ka indicate that the δ13C variations responded to net evaporation changes. Negative shifts in the n-alkane δ13C values coinciding with the ACL decreases at 10.5-9.3 ka and 8.1 ka indicate the short-term onset and fluctuations of the summer monsoon strength in eastern China during the early Holocene
A new method for the Characterization of Strain-Specific Conformational Stability of Protease-Sensitive and Protease Resistant PrPSc
No full textAlthough proteinacious in nature, prions exist as strains with specific self-perpetuating biological properties. Prion strains are thought to be associated with different conformers of PrPSc, a disease-associated isoform of the host-encoded cellular protein (PrPC). Molecular strain typing approaches have been developed which rely on the characterization of protease-resistant PrPSc. However, PrPSc is composed not only of protease-resistant but also of protease-sensitive isoforms. The aim of this work was to develop a protocol for the molecular characterization of both, protease-resistant and protease-sensitive PrPSc aggregates. We first set up experimental conditions which allowed the most advantageous separation of PrPC and PrPSc by means of differential centrifugation. The conformational solubility and stability assay (CSSA) was then developed by measuring PrPSc solubility as a function of increased exposure to GdnHCl. Brain homogenates from voles infected with human and sheep prion isolates were analysed by CSSA and showed strain-specific conformational stabilities, with mean [GdnHCl]1/2 values ranging from 1.6 M for MM2 sCJD to 2.1 for scrapie and to 2.8 M for MM1/MV1 sCJD and E200K gCJD. Interestingly, the rank order of [GdnHCl]1/2 values observed in the human and sheep isolates used as inocula closely matched those found following transmission in voles, being MM1 sCJD the most resistant (3.3 M), followed by sheep scrapie (2.2 M) and by MM2 sCJD (1.6 M). In order to test the ability of CSSA to characterise protease-sensitive PrPSc, we analysed sheep isolates of Nor98 and compared them to classical scrapie isolates. In Nor98, insoluble PrPSc aggregates were mainly protease-sensitive and showed a conformational stability much lower than in classical scrapie. Our results show that CSSA is able to reveal strain-specified PrPSc conformational stabilities of protease-resistant and protease-sensitive PrPSc and that it is a valuable tool for strain typing in natural hosts, such as humans and sheep
Isolation and characterization of Alicycliphilus denitrificans strain BC, which grows on benzene with chlorate as the electron acceptor
No full textA bacterium, strain BC, was isolated from a benzene-degrading chlorate-reducing enrichment culture. Strain BC degrades benzene in conjunction with chlorate reduction. Cells of strain BC are short rods that are 0.6 microm wide and 1 to 2 microm long, are motile, and stain gram negative. Strain BC grows on benzene and some other aromatic compounds with oxygen or in the absence of oxygen with chlorate as the electron acceptor. Strain BC is a denitrifying bacterium, but it is not able to grow on benzene with nitrate. The closest cultured relative is Alicycliphilus denitrificans type strain K601, a cyclohexanol-degrading nitrate-reducing betaproteobacterium. Chlorate reductase (0.4 U/mg protein) and chlorite dismutase (5.7 U/mg protein) activities in cell extracts of strain BC were determined. Gene sequences encoding a known chlorite dismutase (cld) were not detected in strain BC by using the PCR primers described in previous studies. As physiological and biochemical data indicated that there was oxygenation of benzene during growth with chlorate, a strategy was developed to detect genes encoding monooxygenase and dioxygenase enzymes potentially involved in benzene degradation in strain BC. Using primer sets designed to amplify members of distinct evolutionary branches in the catabolic families involved in benzene biodegradation, two oxygenase genes putatively encoding the enzymes performing the initial successive monooxygenations (BC-BMOa) and the cleavage of catechol (BC-C23O) were detected. Our findings suggest that oxygen formed by dismutation of chlorite can be used to attack organic molecules by means of oxygenases, as exemplified with benzene. Thus, aerobic pathways can be employed under conditions in which no external oxygen is supplie
NRF2 and chemoprevention: signaling, epigenetics and role in intestinal carcinogensis
No full textPrevention is better than cure. The carcinogenesis could take as long as 20 to 30 years to develop from initiated cells to malignant tumor, therefore providing us various opportunities to prevent the appearance of tumors with the use of chemopreventive compounds in the early stage. Chemoprevention becomes an increasing important concept and has led to the intense research about the mechanisms of actions of various chemopreventive compounds. They can be generally classified into blocking agents and suppressing agents. The chemopreventive compounds usually prevent or slow progression of cancer by maintaining a low oxidative stress and inflammatory environment in cells. This is brought about by the activation of Nrf2, the key protein being investigated in our lab. In this dissertation, I will be discussing the use of compounds as suppressing agents and blocking agents, how compounds activates Nrf2 signaling, how novel Nrf2 interaction partner IQGAP1 mediates Nrf2-Keap1 signaling axis, how expression level of Nrf2 could be regulated epigenetically, apart from the well-known post-translational control by Keap1-Ubiquitinase-Protesome axis and finally how loss of Nrf2 could enhance intestinal tumorigenesis in Apc(min/+) mice.Ph.D.Includes bibliographical referencesIncludes vitaby Ka Lung Cheun
Temperature and strain scaling laws for the critical current density in Nb(_3)Sn and Nb(_3)Al conductors in high magnetic fields
No full textDetailed, accurate measurements of critical current density and resistivity to determine the upper critical field have been made on a technological NbsAl conductor in magnetic fields up to 15 T, temperatures from 4.2 K up to the critical temperature and in the strain range from -1.8% to 0.7%. The uncertainty in temperature above 4.2 K was equivalent to ± 100 mK with a stability during the measurements of < 5 mK up to a limiting current of 80 A and a typical noise level of 1 µ Vm(^-1).When B(_c2){T,ε) is defined at 5%pn, 50%pn or 95%/%pn, an empirical relation is found where and an approximate relation, holds. The Jε data were parameterised using F(_p) = J(_E)B = A(ε)[Bc(_2)](^n)b(^p)(1-b)(^9) where b = B/B(_c2)(T,ε). When B(_c2)(T,ε) is constrained to be the value at 50%pn or 95%pn, the scaling law for F(_p) breaks down such that p and q are strong functions of temperature and q is also a strong function of strain. However, when B(_c2)(T,ε) is defined at 5%pn, there is good scaling where p and q are constants independent of temperature and strain. F(_p) can also be approximated by a Kramer form where the Ginzburg-Landau constant is γ is the electronic density of states and is interpreted as the average B(_c2) for the bulk where percolative current flow occurs. The critical current density of Hot Isostatic Pressed (HIP'ed) and unHIP'ed Nb(_3)Sn Modified Jelly Roll wires has also been measured at 4.2 K. The critical current and upper critical field were decreased for the HIP'ed sample. The reduced upper critical field of the HIP'ed wire was found to be less sensitive to strain than the unHIP'ed wire. The exponent of B(_c2) in the flux pinning scaling law increased from 0.86 to 2.14 as a result of the HIP processing
Nearby fibroblasts' response to multiple acupuncture needle revolutions on fibroblast populated collagen gels
No full textAcupuncture is an ancient Chinese healing practice, and an alternative therapy for alleviating pain and chronic disorders. For over twenty years, research is trying to understand the mechanisms that lead to its therapeutic effect. Our laboratory investigates the cellular and molecular events in the connective tissue that occur by acupuncture needling. An in vitro assay was developed to evaluate some of the potential contributors to acupuncture’s effects using a cellular collagen gel as a loose connective tissue mimic. It was hypothesized besides immediate changes to cells under mechanical loading from an acupuncture needle, there were chemical factors released to nearby cells in acupuncture. This thesis investigates whether mechanically stimulating collagen gels with fibroblasts at different revolutions would release chemical factors to nearby fibroblasts where flow cytometry was used to observe cell proliferation as an indicator. Results reveal mechanically stimulating cellular collagen gels at different revolutions does not cause any changes in cell proliferation to nearby cells. However, dead stained mechanically stimulated cellular collagen gels showed cell death occurs around the acupuncture needle. It is possible there were no effects in cell proliferation because when a cellular collagen gel was needle manipulated, some chemical factors were released into the nearby cells. Then as needle manipulation increased, more chemical factors were released, but restricted by the larger amount of cell death around the needle from the increasing rotation.M.S.Includes bibliographical referencesby Ka Po Ch
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