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Substantial Decrease (substantial + decrease)
Selected AbstractsPorcine Plasma Proteins as a Surimi Protease Inhibitor: Effects on Actomyosin GelationJOURNAL OF FOOD SCIENCE, Issue 4 2000W. Visessanguan ABSTRACT Effect of porcine plasma proteins (PPP) on thermal gelation of actomyosin in the presence and absence of fish proteinase was studied using a dynamic rheological test. Substantial decreases in development rate and magnitude of gel modulus were observed by the addition of proteinase to actomyosin gels. PPP was effective in protecting a myosin-heavy chain from proteolytic degradation, however, PPP itself interfered with the formation of actomyosin gel. Lower gel modulus was observed with actomyosin gels developed with higher concentrations of PPP added. Overall, PPP reversed the loss of gel modulus by the proteinase, however, the recovered gel modulus was only as high as those containing PPP only. These results implicated that, although PPP may revert autolytic activity in surimi, it interfaces with actomyosin gelation. [source] Onco-miR-155 targets SHIP1 to promote TNF,-dependent growth of B cell lymphomasEMBO MOLECULAR MEDICINE, Issue 5 2009Irene M. Pedersen Abstract Non-coding microRNAs (miRs) are a vital component of post-transcriptional modulation of protein expression and, like coding mRNAs harbour oncogenic properties. However, the mechanisms governing miR expression and the identity of the affected transcripts remain poorly understood. Here we identify the inositol phosphatase SHIP1 as a bonafide target of the oncogenic miR-155. We demonstrate that in diffuse large B cell lymphoma (DLBCL) elevated levels of miR-155, and consequent diminished SHIP1 expression are the result of autocrine stimulation by the pro-inflammatory cytokine tumour necrosis factor , (TNF,). Anti-TNF, regimen such as eternacept or infliximab were sufficient to reduce miR-155 levels and restored SHIP1 expression in DLBCL cells with an accompanying reduction in cell proliferation. Furthermore, we observed a substantial decrease in tumour burden in DLBCL xenografts in response to eternacept. These findings strongly support the concept that cytokine-regulated miRs can function as a crucial link between inflammation and cancer, and illustrate the feasibility of anti-TNF, therapy as a novel and immediately accessible (co)treatment for DLBCL. [source] Ion transport and osmotic adjustment in Escherichia coli in response to ionic and non-ionic osmoticaENVIRONMENTAL MICROBIOLOGY, Issue 1 2009Lana Shabala Summary Bacteria respond to osmotic stress by a substantial increase in the intracellular osmolality, adjusting their cell turgor for altered growth conditions. Using Escherichia coli as a model organism we demonstrate here that bacterial responses to hyperosmotic stress specifically depend on the nature of osmoticum used. We show that increasing acute hyperosmotic NaCl stress above ,1.0 Os kg,1 causes a dose-dependent K+ leak from the cell, resulting in a substantial decrease in cytosolic K+ content and a concurrent accumulation of Na+ in the cell. At the same time, isotonic sucrose or mannitol treatment (non-ionic osmotica) results in a gradual increase of the net K+ uptake. Ion flux data are consistent with growth experiments showing that bacterial growth is impaired by NaCl at the concentration resulting in a switch from net K+ uptake to efflux. Microarray experiments reveal that about 40% of upregulated genes shared no similarity in their responses to NaCl and sucrose treatment, further suggesting specificity of osmotic adjustment in E. coli to ionic and non-ionic osmotica. The observed differences are explained by the specificity of the stress-induced changes in the membrane potential of bacterial cells highlighting the importance of voltage-gated K+ transporters for bacterial adaptation to hyperosmotic stress. [source] Trajectories of smoking among freshmen college students with prior smoking history and risk for future smoking: data from the University Project Tobacco Etiology Research Network (UpTERN) studyADDICTION, Issue 9 2008Craig R. Colder ABSTRACT Aims Little is known about smoking during the transition to college. The current study examined trajectories of smoking among college freshmen, how trajectories predicted later smoking and the social context of smoking. Design Weekly assessments of daily smoking were collected via the web during the first year of college for a large cohort with a previous history of smoking. Participants and setting A total of 193 college freshmen from a large public university with a previous history of smoking who smoked frequently enough to be included in trajectory analysis. Measurements Measures included weekly reports of daily smoking, family smoking, perceived peer attitudes and smoking, social norms and social smoking environment. Findings Seven trajectories were identified: one of low-level sporadic smoking, one of low-level smoking with a small increase during the year, two classes with a substantial decrease during the year, two classes with relatively small decreases and one class with a substantial increase in smoking. Trajectories of smoking in the freshman year predicted levels of sophomore year smoking, and some social context variables tended to change as smoking increased or decreased for a given trajectory class. Conclusions The transition into college is marked by changes in smoking, with smoking escalating for some students and continuing into the sophomore year. Shifts in social context that support smoking were associated with trajectories of smoking. Despite the focus of developmental models on smoking in early adolescence, the transition into college warrants further investigation as a dynamic period for smoking. [source] Microsomal triglyceride transfer protein regulates endogenous and exogenous antigen presentation by group,1 CD1 moleculesEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2008Arthur Kaser Abstract Lipid antigens are presented to T cells by the non-polymorphic MHC class,I-related CD1 molecules. Microsomal triglyceride transfer protein (MTP) is an endoplasmic reticulum (ER)-resident chaperone that has been shown to lipidate the group,2 CD1 molecule CD1d and thus to regulate its function. We now report that MTP also regulates the function of group,1 CD1 molecules CD1a, CD1b, and CD1c. Pharmacological inhibition of MTP in monocyte-derived dendritic cells and lymphoblastoid B cell lines transfected with group,1 CD1 resulted in a substantial decrease in endogenous self lipid antigen presentation to several CD1-restricted T cell lines. Silencing MTP expression in CD1c-transfected HeLa cells similarly resulted in decreased self reactivity. Unexpectedly, inhibition of ER-resident MTP, which was confirmed by confocal microscopy, also markedly decreased presentation of exogenous, endosomally loaded, mycobacterial lipid antigens by CD1a and CD1c to T cells. Thus, these studies indicate that MTP, despite its ER localization, regulates endogenous as well as exogenous lipid antigen presentation, and suggest a broad role for MTP in the regulation of CD1 antigen presentation. [source] Accumulation of heterocyclic nitrogen in humified organic matter: a 15N-NMR study of lowland rice soilsEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 3 2000N. Mahieu Summary Recent intensification of cropping and the attendant longer submergence of the soil for lowland rice in tropical Asia appear to have altered the nature of the soil organic matter, and perhaps also nutrient cycling. To identify the dominant forms of organic nitrogen in the soils we extracted the labile mobile humic acid (MHA) and the more recalcitrant calcium humate (CaHA) fractions from soils under several long-term field experiments in the Philippines and analysed them by 15N-nuclear magnetic resonance spectroscopy. Amide N dominated the spectra of all humic acid (HA) samples (60,80% of total peak area). Its proportion of total spectral area increased with increasing intensity of cropping and length of time during which the soil was flooded and was greater in the MHA fraction than in the CaHA fraction. Simultaneously the spectral proportion of free amino N and other chemical shift regions decreased slightly with increasing length of submergence. Heterocyclic N was detected at modest proportions (7,22%) and was more prevalent in more humified samples, especially in the CaHA of aerated soils. Correlations of spectral proportions of heterocyclic N with other properties of the HA, reported elsewhere, were highly significant. Correlations were positive with visible light absorption (r=,0.86) and concentration of free radicals (r=,0.85), both of which are indices of humification, and negative with concentration of H (r=,,0.86), a negative index of humification. Correlations of spectral proportions of amide N with these properties were also highly significant but in each case of opposite sign to that of heterocyclic N. Proportions of heterocyclic N declined with increasing duration of submergence. The results suggest that (i) 15N-NMR can reproducibly measure some portion of heterocyclic N, (ii) formation of heterocyclic N is associated solely with gradual humification occurring over many years, and (iii) the abundant phenols in the submerged rice soils did not promote formation of heterocyclic N, and hence some other process is responsible for a substantial decrease in the availability of native N associated with intensive rice cropping. [source] Dynamics, stability and iron-binding activity of frataxin clinical mutantsFEBS JOURNAL, Issue 14 2008Ana R. Correia Friedreich's ataxia results from a deficiency in the mitochondrial protein frataxin, which carries single point mutations in some patients. In the present study, we analysed the consequences of different disease-related mutations in vitro on the stability and dynamics of human frataxin. Two of the mutations, G130V and D122Y, were investigated for the first time. Analysis by CD spectroscopy demonstrated a substantial decrease in the thermodynamic stability of the variants during chemical and thermal unfolding (wild-type > W155R > I154F > D122Y > G130V), which was reversible in all cases. Protein dynamics was studied in detail and revealed that the mutants have distinct propensities towards aggregation. It was observed that the mutants have increased correlation times and different relative ratios between soluble and insoluble/aggregated protein. NMR showed that the clinical mutants retained a compact and relatively rigid globular core despite their decreased stabilities. Limited proteolysis assays coupled with LC-MS allowed the identification of particularly flexible regions in the mutants; interestingly, these regions included those involved in iron-binding. In agreement, the iron metallochaperone activity of the Friedreich's ataxia mutants was affected: some mutants precipitate upon iron binding (I154F and W155R) and others have a lower binding stoichiometry (G130V and D122Y). Our results suggest that, in heterozygous patients, the development of Friedreich's ataxia may result from a combination of reduced efficiency of protein folding and accelerated degradation in vivo, leading to lower than normal concentrations of frataxin. This hypothesis also suggests that, although quite different from other neurodegenerative diseases involving toxic aggregation, Friedreich's ataxia could also be linked to a process of protein misfolding due to specific destabilization of frataxin. [source] P2Y13 receptor is critical for reverse cholesterol transport,HEPATOLOGY, Issue 4 2010Aurélie C. Fabre A major atheroprotective functionality of high-density lipoproteins (HDLs) is to promote "reverse cholesterol transport" (RCT). In this process, HDLs mediate the efflux and transport of cholesterol from peripheral cells and its subsequent transport to the liver for further metabolism and biliary excretion. We have previously demonstrated in cultured hepatocytes that P2Y13 (purinergic receptor P2Y, G protein,coupled, 13) activation is essential for HDL uptake but the potential of P2Y13 as a target to promote RCT has not been documented. Here, we show that P2Y13 -deficient mice exhibited a decrease in hepatic HDL cholesterol uptake, hepatic cholesterol content, and biliary cholesterol output, although their plasma HDL and other lipid levels were normal. These changes translated into a substantial decrease in the rate of macrophage-to-feces RCT. Therefore, hallmark features of RCT are impaired in P2Y13 -deficient mice. Furthermore, cangrelor, a partial agonist of P2Y13, stimulated hepatic HDL uptake and biliary lipid secretions in normal mice and in mice with a targeted deletion of scavenger receptor class B type I (SR-BI) in liver (hypomSR-BI,knockoutliver) but had no effect in P2Y13 knockout mice, which indicate that P2Y13 -mediated HDL uptake pathway is independent of SR-BI,mediated HDL selective cholesteryl ester uptake. Conclusion: These results establish P2Y13 as an attractive novel target for modulating RCT and support the emerging view that steady-state plasma HDL levels do not necessarily reflect the capacity of HDL to promote RCT. (HEPATOLOGY 2010) [source] Causes for the decline of suspended-sediment discharge in the Mississippi River system, 1940,2007,HYDROLOGICAL PROCESSES, Issue 1 2010Robert H. Meade Abstract Before 1900, the Missouri,Mississippi River system transported an estimated 400 million metric tons per year of sediment from the interior of the United States to coastal Louisiana. During the last two decades (1987,2006), this transport has averaged 145 million metric tons per year. The cause for this substantial decrease in sediment has been attributed to the trapping characteristics of dams constructed on the muddy part of the Missouri River during the 1950s. However, reexamination of more than 60 years of water- and sediment-discharge data indicates that the dams alone are not the sole cause. These dams trap about 100,150 million metric tons per year, which represent about half the decrease in sediment discharge near the mouth of the Mississippi. Changes in relations between water discharge and suspended-sediment concentration suggest that the Missouri,Mississippi has been transformed from a transport-limited to a supply-limited system. Thus, other engineering activities such as meander cutoffs, river-training structures, and bank revetments as well as soil erosion controls have trapped sediment, eliminated sediment sources, or protected sediment that was once available for transport episodically throughout the year. Removing major engineering structures such as dams probably would not restore sediment discharges to pre-1900 state, mainly because of the numerous smaller engineering structures and other soil-retention works throughout the Missouri,Mississippi system. Published in 2009 by John Wiley & Sons, Ltd. [source] Reduction of TIP30 correlates with poor prognosis of gastric cancer patients and its restoration drastically inhibits tumor growth and metastasisINTERNATIONAL JOURNAL OF CANCER, Issue 3 2009Xiaohua Li Abstract Gastric cancer is an aggressive cancer with poor prognosis. Identification of precise prognostic marker and effective therapeutic target is important in the treatment of gastric cancer. TIP30, a newly identified tumor suppressor, appears to be involved in multiple functions including tumorigenic suppression, apoptosis induction and diminishing angiogenic properties. Here, the level of TIP30 expression was determined in gastric cancer, and the impact of its alteration on cancer biology and clinical outcome was investigated. We found that TIP30 protein was absent or reduced in gastric cancer cell lines. There was also a loss or substantial decrease of TIP30 expression in 106 cases of gastric tumors as compared with that in normal gastric mucosa (p < 0.05), which was significantly associated with inferior survival duration. In a Cox proportional hazards model, TIP30 expression independently predicted better survival (p < 0.05). We also restored TIP30 protein expression in human gastric cancer-derived cells AGS and MKN28 lacking endogenous TIP30 protein to study the effects of TIP30 expression on cell proliferation, cell kinetics, tumorigenicity and metastasis in BALB/c nude mice and found that adenoviral-mediated restoration of TIP30 expression led to downregulation of cyclin D1, Bcl-2, Bcl-xl, but to upregulation of p27, Bax, p53, caspase 3 and 9 expression, cell cycle G0/G1 arrest and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Taken together, the present work revealed a novel function of TIP30, which can possibly be used as an independent prognostic factor and a potential therapeutic target for gastric cancer. © 2008 Wiley-Liss, Inc. [source] Characteristics of wintertime daily and extreme minimum temperature over South KoreaINTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 2 2004Sang-Boom Ryoo Abstract In South Korea, consecutive positive temperature anomalies have been observed since the mid-1980s. The objective of this study is to assess the recent trends in, and variability of, daily minimum temperature over South Korea with particular emphasis on its extremes. Temporal characteristics of wintertime daily and extreme minimum temperature-related variables were analysed on a seasonal basis for the period of 1958,59 to 2000,01. The results show continually fewer days with extreme low minimum temperature since the mid-1980s. However, no significant change in the 1 day temperature difference was observed during the same period, indicating little change in the frequency of cold surges. Also, during the period analysed, there is a significant positive trend in the seasonal mean temperature, a negative trend in the frequency of the extreme cold days, and no significant trend in the seasonal occurrence of cold surges. Northern Hemisphere geopotential height fields before and after 1986,87, i.e. the start of successive positive anomalies in the winter surface air temperature over South Korea, showed a substantial decrease throughout the troposphere over the polar region. In the upper levels the overall pattern becomes more wavelike, with eddies embedded between meanders. The differences in the lower troposphere are remarkably similar to the Arctic oscillation, although the centre in the North Atlantic is shifted toward western Europe and differences in the North Pacific are relatively weaker than those in the polar region. The recent positive phase of the Arctic oscillation may contribute to these abrupt changes in wintertime daily minimum temperatures over South Korea. El Niño,southern oscillation phenomena appear to contribute to the interannual variation of cold surge days in South Korea. Years with no cold surges were experienced during La Niña episodes. On the other hand, all years with more than four cases of cold surges were during El Niño episodes. Copyright © 2004 Royal Meteorological Society [source] Synchrotron studies of polymers at DND-CATJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 3-1 2000J.D. Londono Two examples are presented that illustrate the capabilities of DND-CAT instrumentation for the study of the effects of processing on polymers. Firstly, a thermoplastic elastomer, Hytrel®, was stretched while 2-D data were collected simultaneously. The Hytrel® data show that the yield point of the stress-strain curve is associated with the sudden appearance of a four-point pattern. At higher deformations, strain-induced crystallization and the destruction of the hard segment domains lead to a substantial decrease of the contrast as monitored by the SAXS invariant. Prior to breakage, the extent and intensity of an equatorial streak develops as the material fibrillates. Secondly, SAXS and WAXS data were collected from quenched and annealed Poly(ethylene terephthalate) (PET) samples mounted on a DSC cell, to characterize the pre-melting shoulder in this material. Results show that substantial melting and re-crystallization occurs within the range of this shoulder in the quenched sample. [source] Bush encroachment under three contrasting land-use practices in a mesic South African savannaAFRICAN JOURNAL OF ECOLOGY, Issue 2009B. J. Wigley Abstract This study determined the effects of land-use practice had on the rate and extent of bush encroachment in a mesic savanna in KwaZulu-Natal, South Africa. Changes in woody cover were measured for 1 km2 sites in areas under communal, commercial and conservation land-use systems for the period between 1937 and 2000. Land users from each area were interviewed to gain the histories of each area and to determine how the changes in woody cover had impacted them and whether anything was being done to counteract the spread of trees and shrubs on their land. Bush encroachment occurred across all three of the land-use types in the 67-year period between 1937 and 2000. The results showed that land-use practice had enormous impacts on the process of bush encroachment. The communal site showed a decrease in grass (21%) and tree (5%) cover and an increase in shrub cover (13%). At the commercial site, there was a considerable decrease in grass cover (46%) and moderate increase in shrub cover (10%) and a massive increase in tree cover (36%). The area under conservation showed a substantial decrease in grass cover (47%), a slight decrease in shrub cover (19%) and a massive increase in tree cover (66%). The perceived causes of these changes were fairly similar amongst the different land users. The changes were mostly not perceived to be a problem for the communal land users. The main advantages mentioned were increased woody resources for building and firewood and increased browse availability. The commercial and conservation land users perceived the changes to have significant negative connotations including the loss of grazing land and biodiversity and secondary invasion of encroached areas by alien plant species. Despite these perceptions, very little has been done to combat bush encroachment in the commercial and conservation land use systems. [source] Photochemistry of 4- and 5- phenyl substituted isoxazolesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 2 2005James W. Pavlik 5-Phenylisoxazole (4) and 4-phenylisoxazole (22) underwent phototransposition to 5-phenyloxazole (5) and 4-phenyloxazole (24) respectively. Labeling with deuterium or methyl confirmed that these phototranspositions occurred via the P4 pathway which involves only interchange of the N2 and C3 ring position. Thus, 4-deuterio-5-phenylisoxazole (4-4d), 4-methyl-5-phenylisoxazole (10), and 5-methyl-4-phenylisoxazole (23) phototransposed to 4-deuterio-5-phenyloxazole (5-4d), 4-methyl-5-phenyloxazole (11), and 5-methyl-4-phenyloxazole (25) respectively. In addition to phototransposition, isoxazoles 4, 10, and 23 also underwent photo-ring cleavage to yield benzoylacetonitrile (9), ,-benzoylpropionitrile (15), and aceto-,-phenylacetonitrile (26) respectively. Irradiation of 5-phenyl-3-(trifluoromethyl)isoxazole (16) in acetonitrile led to 5-phenyl-2-(trifluoromethyl)oxazole (17), the P4 phototransposition product. Irradiation of 16 in methanol led to a substantial decrease in the yield of 17 and to the formation of a mixture of (E) and (Z)-2-methoxy-2-(trifluoromethyl)-3-benzoylaziridines 18a and 18b. [source] Improved myelin water quantification using spatially regularized non-negative least squares algorithmJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2009Dosik Hwang PhD Abstract Purpose To improve the myelin water quantification in the brain in the presence of measurement noise and to increase the visibility of small focal lesions in myelin-water-fraction (MWF) maps. Materials and Methods A spatially regularized non-negative least squares (srNNLS) algorithm was developed for robust myelin water quantification in the brain. The regularization for the conventional NNLS algorithm was expanded into the spatial domain in addition to the spectral domain. Synthetic data simulations were performed to study the effectiveness of this new algorithm. Experimental free-induction-decay measurements were obtained using a multi-gradient-echo pulse sequence and MWF maps were estimated using the srNNLS algorithm. The results were compared with other conventional methods. Results A substantial decrease in MWF variability was observed in both simulations and experimental data when the srNNLS algorithm was applied. As a result, false lesions in the MWF maps disappeared and the visibility of small focal lesions improved greatly. On average, the contrast-to-noise ratio for focal lesions was improved by a factor of 2. Conclusion The MWF variability due to the measurement noise can be substantially reduced and the detection of small focal lesions can be improved by using the srNNLS algorithm. J. Magn. Reson. Imaging 2009;30:203,208. © 2009 Wiley-Liss, Inc. [source] Inhibition of neural activity depletes orexin from rat hypothalamic slice cultureJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2010Shotaro Michinaga Abstract Orexins (hypocretins) are neuropeptides produced by a small population of hypothalamic neurons whose dysregulation may lead to narcolepsy, a neurological disorder characterized by disorganization of sleep and wakefulness. Excessive stimulation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors causes preferential loss of orexin neurons in the hypothalamus, whereas an adequate level of neuronal excitatory activities is generally known to be important for the maintenance of central neurons. By examining the effect of manipulation of neural activity, we found that 24,72 hr application of tetrodotoxin (TTX) caused a substantial decrease in the number of orexin-immunoreactive neurons, but not of melanin-concentrating hormone-immunoreactive neurons, in hypothalamic slice culture. Similar results were obtained when neural activity was arrested by added extracellular Mg2+. Reduction of orexin expression by TTX and Mg2+ was also observed at mRNA level. The decrease of orexin-immunoreactive neurons was attributable to depletion of orexin, because it was reversible after washout of TTX or elevated extracellular Mg2+ and was not associated with induction of cell death. Blockers of voltage-dependent Ca2+ channels as well as of NMDA receptors also induced a significant and selective decrease of orexin-immunoreactive neurons. Moreover, TTX-induced decrease of orexin immunoreactivity was largely abrogated by concurrent application of a moderate concentration of NMDA. These results suggest that Ca2+ entry associated with nontoxic levels of spontaneous activity of glutamatergic inputs plays an important role in the maintenance of orexin neurons in a tissue culture model. © 2009 Wiley-Liss, Inc. [source] Fluorescein-labeled stable neurotensin derivativesJOURNAL OF PEPTIDE SCIENCE, Issue 8 2006Veronique Maes Abstract Neurotensin(8-13) analogs containing a glycine or 5-aminovaleroyl spacer were labeled with fluorescein through formation of an N -terminal thiourea function. The receptor binding was measured in HT-29 cell cultures and showed a substantial decrease in affinity, especially for the metabolically stabilized [MeArg9, Tle11] analog. Using fluorescence microscopy, the internalization of the fluorescent neurotensin analogs into HT-29 cells was observed. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd. [source] Synthesis, conformation and biological activity of linear and cyclic Thr6 -bradykinin analogues containing N -benzylglycine in place of phenylalanine,JOURNAL OF PEPTIDE SCIENCE, Issue 12 2001L. Biondi Abstract Three linear Thr6 -bradykinin analogues in which either one or both the two phenylalanine residues in the peptide sequence have been substituted by N -benzylglycine (BzlGly) and their head-to-tail cyclic analogues were synthesized and tested on an isolated rat duodenum preparation. The linear (BzlGly5,Thr6 -BK, BzlGly8,Thr6 -BK and BzlGly5,8,Thr6 -BK) and the cyclic (cyclo BzlGly5,Thr6 -BK, cyclo BzlGly8,Thr6 -BK and cyclo BzlGly5,8,Thr6 -BK) peptoid-like analogues were characterized by amino acid analysis, optical rotation, analytical HPLC and MALDI-TOF mass spectroscopy. The conformational features of both the linear and cyclic derivatives were investigated by FT-IR and CD measurements. Preliminary molecular mechanics calculations were also performed on some synthetic peptides. Pharmacological screening using the relaxation of the isolated rat duodenum preparation showed that incorporation of N -benzylglycine at positions 5 and/or 8 in the linear Thr6 -BK causes a substantial decrease in potency. Comparable incorporation in cyclo Thr6 -BK, at position 8, or 5 and 8, resulted in nearly inactive analogues. However, cyclo BzlGly5,Thr6 -BK showed a potency which is of the same order of magnitude as for cyclo -BK and cyclo Thr6 -BK. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source] Leptin levels in gingival crevicular fluid in periodontal health and diseaseJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2007B. V. Karthikeyan Background and Objective:, A high concentration of leptin is associated with healthy gingival tissue, and the concentration of leptin decreases as periodontal disease progresses. However, to date, the leptin concentration in gingival crevicular fluid has not been documented. Hence, the present study was carried out to explore the presence of leptin in gingival crevicular fluid in periodontal health and disease, and to probe further into its possible role in periodontal disease progression. Material and Methods:, A total of 45 adult patients were selected, based on their body mass index, for the study. They were categorized into three groups of 15 patients each, based on their periodontal tissue status, as follows: group I (clinically healthy gingiva with no loss of attachment); group II (chronic gingivitis with no loss of attachment); and group III (chronic periodontitis). Gingival crevicular fluid samples of 1 µL were collected extracrevicularly using white color-coded 1,5 µL calibrated volumetric microcapillary pipettes from one site in each person, and samples were analyzed for leptin using a commercially available enzyme-linked immunosorbent assay kit. Results:, The concentration of leptin in gingival crevicular fluid of patients in group I (2292.69 pg/mL) was statistically higher (p < 0.05) than in those of groups II (1409.95 pg/mL) and III (1071.89 pg/mL). This suggests a negative correlation of gingival crevicular fluid leptin concentration with clinical attachment loss (p < 0.05). Conclusion:, As periodontal tissue destruction increased, there was a substantial decrease in gingival crevicular fluid leptin concentration. This observation extends our knowledge of the protective role of leptin in periodontal health. [source] The large form of ADAR 1 is responsible for enhanced hepatitis delta virus RNA editing in interferon- , -stimulated host cellsJOURNAL OF VIRAL HEPATITIS, Issue 3 2006D. Hartwig Summary., Hepatitis delta virus (HDV) RNA editing controls the formation of hepatitis-delta-antigen-S and -L and therefore indirectly regulates HDV replication. Editing is thought to be catalysed by the adenosine deaminase acting on RNA1 (ADAR1) of which two different forms exist, interferon (IFN)- , -inducible ADAR1-L and constitutively expressed ADAR1-S. ADAR1-L is hypothesized to be a part of the innate cellular immune system, responsible for deaminating adenosines in viral dsRNAs. We examined the influence of both forms on HDV RNA editing in IFN- , -stimulated and unstimulated hepatoma cells. For gene silencing, an antisense oligodeoxyribonucleotide against a common sequence of both forms of ADAR1 and another one specific for ADAR1-L alone were used. IFN- , treatment of host cells led to approximately twofold increase of RNA editing compared with unstimulated controls. If ADAR1-L expression was inhibited, this substantial increase in editing could no longer be observed. In unstimulated cells, ADAR1-L suppression had only minor effects on editing. Inhibition of both forms of ADAR1 simultaneously led to a substantial decrease of edited RNA independently of IFN- , -stimulation. In conclusion, the two forms of ADAR1 are responsible almost alone for HDV editing. In unstimulated cells, ADAR1-S is the main editing activity. The increase of edited RNA under IFN- , -stimulation is because of induction of ADAR1-L, showing for the first time that this IFN-inducible protein is involved in the base modification of replicating HDV RNA. Thus, induction of ADAR1-L may at least partially cause the antiviral effect of IFN- , in natural immune response to HDV as well as in case of therapeutic administration of IFN. [source] Reinvestigation of the Mechanism of the Free Radical Polymerization Photoinitiation Process by Camphorquinone,Coinitiator Systems: New ResultsMACROMOLECULAR CHEMISTRY AND PHYSICS, Issue 17 2004Ilona Pyszka Abstract Summary: Comparative studies of photoinitiation processes using camphorquinone (CQ) and benzophenone (BP) as light absorbers were performed. The experimental results show that after the transformation of (phenylthio)acetic acid (PTAA) into its tetrabutylammonium salt (PTAA AS), a substantial decrease of the polymerization photoinitiation ability for the CQ,PTAA AS pair in comparison to the CQ,PTAA pair is observed. The mechanism of the photoinitiated polymerization for the tested photoredox pair was clarified based on laser flash photolysis experiments obtained using benzophenone as an electron acceptor and (phenylthio)acetic acid and its tetrabutylammonium salt as electron donors in solution in MeCN. It is documented and deduced that the photoreduction of benzophenone in the presence of (phenylthio)acetic acid and its tetrabutylammonium salt occurs by a photoinduced electron transfer process, while for CQ as initiator, the free radicals are formed by hydrogen atom abstraction by the triplet state of camphorquinone. Schematic of the transients formed after an electron-transfer process for benzophenone,PTAA and benzophenone,PTAA AS pairs. [source] Compatibilization of Immiscible Poly(propylene)/Polystyrene Blends Using ClayMACROMOLECULAR RAPID COMMUNICATIONS, Issue 3 2003Yong Wang Abstract Inorganic clay was investigated as a compatibilizer for immiscible poly(propylene)/polystyrene blends. A substantial decrease in the number of polystyrene particles was seen after adding small amounts of an organically treated clay (2,5 wt.-%) to the blends. A possible mechanism for this kind of compatibilization is discussed, but these unique and completely new findings need further verification. Schematic representation of the intercalated structure in PP/PS/OMMT blends: (a) PP and PS confined in the same gallery of OMMT, and (b) parts of PP and PS molecules located outside the gallery serving as a compatibilizer. [source] Women's narratives on experiences of work ability and functioning in fibromyalgiaMUSCULOSKELETAL CARE, Issue 1 2010Merja Sallinen MSc Abstract Background:,Fibromyalgia is a significant health problem for women of working age. However, little is known about the long-term effects of fibromyalgia in everyday life or on work ability. Methods:,A narrative interview study was conducted to explore the experiences of work ability and functioning of patients with a long history of fibromyalgia. Twenty women, aged 34,65 years, were purposively chosen for the interviews, to reach a wide range of patients with different social and professional backgrounds. Results:,Four types of experience concerning work ability were identified in the narratives: confusion, coping with fluctuating symptoms, being ,in between' and being over the edge of exhaustion. Severe pain and fatigue symptoms, combined with a demanding life situation and ageing, seemed to lead to substantial decrease in work ability and functioning over the long term. In the narratives, vocational rehabilitation or adjustments to work tasks were rarely seen or were started too late to be effective. Conclusions:,Exploring the life stories of women with fibromyalgia can reveal the perceived causes and consequences of fibromyalgia related to work ability or disability, which can be utilized in developing client-centred rehabilitation approaches and effective interventions to support work ability and avoid premature retirement in fibromyalgia patients. Copyright © 2009 John Wiley & Sons, Ltd. [source] Effects of Drought on the Competitive Interference of an Early Successional Species (Rubus fruticosus) on Fagus sylvatica L. Seedlings: 15N Uptake and Partitioning, Responses of Amino Acids and other N CompoundsPLANT BIOLOGY, Issue 3 2002M. N. Fotelli Abstract: We assessed the role of water availability as a factor regulating the ability of beech seedlings to cope with competitive interference for nitrogen resources by an early successional species (Rubus fruticosus). A glasshouse experiment was performed with two levels of interference (beech with and without R. fruticosus) and three levels of irrigation (high, intermediate, none). 15N uptake and partitioning of both species, and composition of N pools in leaves, roots and phloem of beech, were determined. Under all irrigation regimes, 15N uptake by beech seedlings decreased when grown together with R. fruticosus. R. fruticosus had higher 15N uptake rates than beech, under all water supply levels. When irrigation was reduced, a substantial decrease in 15N uptake of beech seedlings and a concurrent increase in 15N uptake by R. fruticosus were observed. Interference by R. fruticosus and low irrigation also affected the 15N partitioning in beech seedlings and resulted in reduced allocation of 15N to the roots. The combination of competitive interference and lack of irrigation led to an increase in soluble non-protein N in roots and leaves of beech, due to protein degradation. This response was attributed to an increase in levels of amino acids serving as osmoprotectants under these conditions. The concentration of proline in leaves of beech was negatively correlated to shoot water potential. A competition-induced reduction of total N in leaves of beech under high and intermediate irrigation was found. These results illustrate (1) the advantage of R. fruticosus in terms of N uptake when compared to young beech, particularly under inadequate water supply, and (2) the changes in N composition of beech seedlings in order to cope with reduced soil water and interference by R. fruticosus. [source] Barrier properties of blends based on liquid crystalline polymers and polyethylenePOLYMER ENGINEERING & SCIENCE, Issue 9 2000G. Flodberg Blends of an extrusion-grade polyethylene and two different liquid crystalline polymers of Vectra type were prepared by melt mixing using poly(ethylene-comethacrylic acid) as compatibilizer. Oxygen and water vapor permeability, transparency and welding strength of compression molded and film blown specimens were studied. The compression molded blends showed gas permeabilities conforming to the Maxwell equation assuming low permeability liquid crystalline polymer spheres in a high permeability polyethylene matrix. One of the liquid crystalline polymers with suitable rheological properties formed a more continuous phase in the film blown blends and a substantial decrease in oxygen and water vapor permeability was observed in these blends. The compression molded blends with 50% liquid crystalline polymer and some of blow molded blends showed very high gas permeabilities. It is believed that voids forming continuous paths through the structure were present in these samples. The blends showed significantly higher opacity than pure polyethylene. [source] Probing mechanisms of resistance to the tuberculosis drug isoniazid: Conformational changes caused by inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosisPROTEIN SCIENCE, Issue 8 2007Nicole A. Kruh Abstract The frontline tuberculosis drug isoniazid (INH) inhibits InhA, the NADH-dependent fatty acid biosynthesis (FAS-II) enoyl reductase from Mycobacterium tuberculosis (MTB), via formation of a covalent adduct with NAD+ (the INH-NAD adduct). Resistance to INH can be correlated with many mutations in MTB, some of which are localized in the InhA cofactor binding site. While the InhA mutations cause a substantial decrease in the affinity of InhA for NADH, surprisingly the same mutations result in only a small impact on binding of the INH-NAD adduct. Based on the knowledge that InhA interacts in vivo with other components of the FAS-II pathway, we have initiated experiments to determine whether enzyme inhibition results in structural changes that could affect protein,protein interactions involving InhA and how these ligand-induced conformational changes are modulated in the InhA mutants. Significantly, while NADH binding to wild-type InhA is hyperbolic, the InhA mutants bind the cofactor with positive cooperativity, suggesting that the mutations permit access to a second conformational state of the protein. While cross-linking studies indicate that enzyme inhibition causes dissociation of the InhA tetramer into dimers, analytical ultracentrifugation and size exclusion chromatography reveal that ligand binding causes a conformational change in the protein that prevents cross-linking across one of the dimer,dimer interfaces in the InhA tetramer. Interestingly, a similar ligand-induced conformational change is also observed for the InhA mutants, indicating that the mutations modulate communication between the subunits without affecting the two conformational states of the protein that are present. [source] Why Current Breast Pathology Practices Must Be Evaluated.THE BREAST JOURNAL, Issue 5 2007A Susan G. Komen for the Cure White Paper: June 200 To this end, the organization has a strong interest and proven track record in ensuring public investment in quality breast health and breast cancer care. Recently, Susan G. Komen for the Cure identified major issues in the practice of pathology that have a negative impact on the lives of thousands of breast cancer patients in the United States. These issues were identified through a comprehensive literature review and interviews conducted in 2005,2006 with experts in oncology, breast pathology, surgery, and radiology. The interviewees practiced in community, academic, and cooperative group settings. Komen for the Cure has identified four areas that have a direct impact on the quality of care breast cancer patients receive in the United States, the accuracy of breast pathology diagnostics, the effects of current health insurance, and reimbursement policies on patients who are evaluated for a possible breast cancer diagnosis, the substantial decrease in tissue banking participation, particularly during a time of rapid advances in biologically correlated clinical science and the role for the Susan G. Komen for the Cure, pathology professional societies and the Federal government in ensuring that breast pathology practices meet the highest possible standards in the United States Concerns surrounding the quality and practice of breast pathology are not limited to diagnostic accuracy. Other considerations include, training and proficiency of pathologists who are evaluating breast specimens, the lack of integration of pathologists in the clinical care team, inadequate compensation for the amount of work required to thoroughly analyze specimens, potential loss in translational research as a result of medical privacy regulations, and the lack of mandatory uniform pathology practice standards without any way to measure the degree of variation or to remedy it. [source] Habitat suitability analysis for lacustrine brown trout (Salmo trutta) in Lake Walchensee, Germany: implications for the conservation of an endangered flagship speciesAQUATIC CONSERVATION: MARINE AND FRESHWATER ECOSYSTEMS, Issue 1 2010Marco Denic Abstract 1.The lacustrine brown trout (Salmo trutta) is endangered and of high conservation importance. In the only spawning habitat of the population in the Bavarian Lake Walchensee, the River Obernach, a substantial decrease in spawning runs has been reported. In this study, the present ecological state of the spawning stream was analysed with the objective of identifying life-stage specific limitations to successful recruitment attributable to deficiencies in (i) spawning migration, (ii) spawning habitat quality, and (iii) habitat quality for juveniles. 2.Structural stream analysis showed that discharge and several migration barriers , particularly near the river outlet into the lake , prevent successful spawning migrations at normal water levels. Migration barriers are probably the main limiting factor for reproduction of lacustrine brown trout, whereas structural variability of the Obernach meets the habitat requirements of both spawners and juveniles. 3.Spawning site quality was suitable for trout, as indicated by stream substratum texture and high exchange rates between free-flowing water and the interstitial zone in physico-chemical parameters (redox potential, dissolved oxygen, pH, temperature and conductivity). 4.Analyses of fish community structure revealed dominance of lithophilic species, in particular of riverine brown trout (Salmo trutta). Its density and intact demographic population structure suggest that spawning and juvenile habitat quality for salmonids is not limiting. Recapture of stocked lacustrine trout juveniles also indicates habitat suitability for the juvenile stage. 5.In conclusion, the results show that the methodology used in this study is suitable for the identification of life-stage specific habitat deficiencies in lacustrine brown trout and other fish species. Availability of habitat data throughout the species' distribution range is a first crucial step for the development of an effective recovery plan. Copyright © 2009 John Wiley & Sons, Ltd. [source] Farming flexibility and food security under climatic uncertainty: Manang, Nepal HimalayaAREA, Issue 2 2010Tor Halfdan Aase Climate change is predicted to cause a substantial decrease in food production in poor regions during this century. But since reliable models of future climates have not been produced at local level as yet, this article focuses on the flexibility of farming systems in terms of adaptability to changing conditions of production, whatever those changes may turn out to be. Defining flexibility as ,uncommitted potentiality for change'Bateson 1972, the aim of the article is to identify such potentialities among subsistence farmers in a remote part of the Himalayas. Our analysis reveals four ,uncommitted potentialities' for adaptation to a future situation that will be climatologically different from the present. In order to maintain local food security under changing climate conditions, farmers in the study valley of Manang can reclaim abandoned land, they can depend more on barley, they may reduce the conspicuous exhibition of horses, and relocate farming from the slope to the valley bottom. The inherent flexibility in their farming system renders Mananges quite robust in facing future uncertainties. Thus, Manang is more appropriately labelled ,dynamic' than ,fragile', which is a term often ascribed to high Himalayan communities and environments. [source] Role of CTA1R7K-COL-DD as a novel therapeutic mucosal tolerance,inducing vector for treatment of collagen-induced arthritisARTHRITIS & RHEUMATISM, Issue 6 2009Annemarie Hasselberg Objective To determine whether a cholera toxin,derived, novel immunomodulating fusion protein, CTA1R7K-COL-DD, carrying the class II major histocompatibility complex H-2q,restricted type II collagen peptide aa 259,274, can induce therapeutic tolerance and prevent collagen-induced arthritis (CIA) when administered intranasally in DBA/1 mice, and to assess whether ADP-ribosylation at the mucosal membranes exerts a regulatory function such that the outcome of tolerance or immune enhancement can be controlled. Methods DBA/1 mice with CIA were treated intranasally with CTA1R7K-COL-DD. The therapeutic effect was monitored for 46 days after the onset of disease. Clinical scoring of disease, histologic examination of inflammation, and bone erosion were assessed, and cytokine levels were determined in the serum or supernatants from splenocytes stimulated with recall antigen. Results The protective effect of CTA1R7K-COL-DD resulted in roughly 60% of the mice having no clinical signs or histologic evidence of disease after treatment, and those with CIA had significantly milder disease with less bone erosion. The protective status was associated with lower serum titers of IgG1, IgG2a, IgG2b, and IgG3 anticollagen and a substantial decrease in the production of interleukin-6 (IL-6), IL-17, and interferon-,, while levels of IL-10 were markedly up-regulated both in the serum and at the T cell level. Conclusion The enzymatically inactive mutant fusion protein CTA1R7K-COL-DD provided substantial therapeutic protection against CIA following intranasal administration. The mechanism behind the effect appears to be mediated by peptide-specific regulatory T cells induced by mucosal exposure to the peptide containing CTA1R7K-COL-DD vector. In addition, ADP-ribosylation at the mucosal membranes acts as a key regulator controlling mucosal tolerance or immunity. [source] | |||||||||||||||||||||||||