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General Mechanism (general + mechanism)
Selected AbstractsCultural variation and the psychological contractJOURNAL OF ORGANIZATIONAL BEHAVIOR, Issue 5 2003David C. Thomas Literature on the psychological contract has made significant contributions to our understanding of the exchange relationship between employees and their employer. However, the influence of cultural differences on perceptions of the employment relationship has largely been neglected. We propose both cognitive and motivational mechanisms through which the cultural profiles of individuals influence (a) formation of the psychological contract, (b) perceptions of violations of the psychological contract, and (c) responses to perceived violations. General mechanisms for the influence of culture on the psychological contract are followed by specific examples of the influence of individualism and collectivism. Copyright © 2003 John Wiley & Sons, Ltd. [source] Adaptive advantages of myrmecochory: the predator-avoidance hypothesis tested over a wide geographic rangeECOGRAPHY, Issue 5 2005Antonio J. Manzaneda The predator-avoidance hypothesis states that once released from the parent plant, myrmecochorous seeds are rapidly taken by ants to their nests, where they are protected from predators. Previous studies conducted to test this hypothesis have frequently neglected two major aspects necessary for its verification: 1) the influence of processes acting after the seed release and 2) the spatial evenness of such processes. Thus, large-scale variations in the mechanisms acting beyond seed release, and possibly influencing seed escape from predators, remain poorly documented. Here, we present the results of a post-dispersal seed-removal experiment on the myrmecochorous herb Helleborus foetidus, aimed at verifing the predator-avoidance hypothesis by considering two key post-release aspects of seed fate: seed destination (dispersed or nondispersed) and seed burial (buried or not buried). Experiments were performed in four different regions in the Iberian Peninsula. After three days of exposure of seeds to the main predator (fieldmice Apodemus sylvaticus), ca 30% of the seeds were removed. Seed destination affected the proportion of seeds escaping predation, but the sign, magnitude and statistical significance of the effect varied among the geographical regions. In the southern region (Cazorla), seeds dispersed in ant nests or intermediate destinations suffered scarcely any predation, but seeds under reproductive-age plants experienced losses ca 50%. Conversely, in the northern region (Caurel), seeds in nests suffered significantly greater losses than seeds under plants or intermediate destinations, suggesting that nests were especially unsafe destinations. Seed burial had a strong impact on seed escape from predators, and its effect was highly consistent among geographical regions. In view of the consistency of its effect at different spatial scales, seed burial was a more general mechanism for predation avoidance than seed relocation to ant nests, which was habitat- and/or ant-species-dependent. Our results thus only partially support the predator-avoidance hypothesis for the evolution of myrmecochory. [source] Visual response augmentation in cat (and macaque) LGN: potentiation by corticofugally mediated gain control in the temporal domainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000Javier Cudeiro Abstract Visual responses of neurons are dependent on the context of a stimulus, not only in spatial terms but also temporally, although evidence for temporally separate visual influences is meagre, based mainly on studies in the higher cortex. Here we demonstrate temporally induced elevation of visual responsiveness in cells in the lateral geniculate nucleus (LGN) of cat and monkey following a period of high intensity (elevated contrast) stimulation. This augmentation is seen in 40,70% (monkey,cat) of cells tested and of all subtypes. Peaking at ,,3 min following the period of intense stimulation, it can last for 10,12 min and can be repeated and summed in time. Furthermore, it is dependent on corticofugal input, is seen even when high contrast stimuli of orthogonal orientation are used and therefore results from a/any prior increase in activity in the retino-geniculo-striate pathway. We suggest that this reflects a general mechanism for control of visual responsiveness; both a flexible and dynamic means of changing effectiveness of thalamic activity as visual input changes, but also a mechanism which is an emergent property of the thalamo-cortico-thalamic loop. [source] Transcription of individual tRNAGly1 genes from within a multigene family is regulated by transcription factor TFIIIBFEBS JOURNAL, Issue 20 2005Akhila Parthasarthy Members of a multigene family from the silkworm Bombyx mori have been classified based on their transcriptions in homologous nuclear extracts, into three groups of highly, moderately and poorly transcribed genes. Because all these gene copies have identical coding sequences and consequently identical promoter elements (the A and B boxes), the flanking sequences modulate their expression levels. Here we demonstrate the interaction of transcription factor TFIIIB with these genes and its role in regulating differential transcriptions. The binding of TFIIIB to the poorly transcribed gene -6,7 was less stable compared with binding of TFIIIB to the highly expressed copy, -1. The presence of a 5, upstream TATA sequence closer to the coding region in -6,7 suggested that the initial binding of TFIIIC to the A and B boxes sterically hindered anchoring of TFIIIB via direct interactions, leading to lower stability of TFIIIC,B-DNA complexes. Also, the multiple TATATAA sequences present in the flanking regions of this poorly transcribed gene successfully competed for TFIIIB reducing transcription. The transcription level could be enhanced to some extent by supplementation of TFIIIB but not by TATA box binding protein. The poor transcription of -6,7 was thus attributed both to the formation of a less stable transcription complex and the sequestration of TFIIIB. Availability of the transcription factor TFIIIB in excess could serve as a general mechanism to initiate transcription from all the individual members of the gene family as per the developmental needs within the tissue. [source] DMD exon 1 truncating point mutations: Amelioration of phenotype by alternative translation initiation in exon 6,HUMAN MUTATION, Issue 4 2009Olga L. Gurvich Abstract Mutations in the DMD gene result in two common phenotypes associated with progressive muscle weakness: the more severe Duchenne muscular dystrophy (DMD) and the milder Becker muscular dystrophy (BMD). We have previously identified a nonsense mutation (c.9G>A; p.Trp3X) within the first exon of the DMD gene, encoding the unique N-terminus of the 427-kDa muscle isoform of the dystrophin protein. Although this mutation would be expected to result in severe disease, the clinical phenotype is very mild BMD, with ambulation preserved into the seventh decade. We identify the molecular mechanism responsible for the amelioration of disease severity to be initiation of translation at two proximate AUG codons within exon 6. Analysis of large mutational data sets suggests that this may be a general mechanism of phenotypic rescue for point mutations within at least the first two exons of the DMD gene. Our results directly demonstrate, for the first time, the use of alternate translational initiation codons within the DMD gene, and suggest that dystrophin protein lacking amino acids encoded by the first five exons retains significant function. Hum Mutat 0:1,8, 2009. © 2009 Wiley-Liss, Inc. [source] The complete mitochondrial genome sequence of the Mormon cricket (Anabrus simplex: Tettigoniidae: Orthoptera) and an analysis of control region variabilityINSECT MOLECULAR BIOLOGY, Issue 2 2007J. D. Fenn Abstract The Anabrus simplex is a swarming plague orthopteran found in western North America. The genome is 15 766 bp in length and genome organization follows the ancestral insect gene arrangement. atp6 lacked any readily identifiable stop codon. Examination of mRNA secondary structure for this gene suggested a stem/loop-mediated mRNA post-transcriptional processing to liberate a mature atp6 mRNA with a complete stop codon produced by polyadenylation. Comparison of similar protein with protein gene boundaries in other insect species reveal a general mechanism for mRNA excision and provide further supporting evidence for post-transcriptional mRNA processing in mitochondrial genomes. The A + T-rich region, or control region, was sequenced for 55 A. simplex individuals from 12 different populations. Variance studies between these individuals show that the A + T-rich region contains significant phylogenetic signal to be used in population studies. [source] Oestrogen imprinting causes nuclear changes in epithelial cells and overall inhibition of gene transcription and protein synthesis in rat ventral prostateINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 5 2010T. M. Augusto Summary Oestrogen exposure during the early post-natal period affects male growth, physiology, and susceptibility to disease in adult life. The prostate gland is susceptible to this oestrogen imprinting, showing a reduced expression of the androgen receptor and inability to respond to androgen stimulus. In this context, we decided to study key signalling regulators of ventral prostate (VP) functioning after early postnatal exposure to high-dose oestrogen. Our results showed a decrease of mTOR phosphorylation and its direct downstream target 4EBP. It is known that mTOR-induced signalling is a pivotal pathway of cell metabolism, which is able to control gene transcription and protein synthesis. We then decided to investigate other indicators of a reduced metabolism in the oestrogenized prostate, and found that the luminal epithelial cells were shorter, less polarized and had smaller nuclei containing more compacted chromatin, suggesting that a general mechanism of regulating gene expression and protein synthesis could be installed in the epithelium of the oestrogenized VP. To evaluate this idea, we analysed nucleolar morphology, and measured the amount of ribosomes and the level of methylation of the 45S ribosomal RNA promoter region. These data indicated that the nucleolus was dismantled and that the methylation at the 45S promoter was increased (,five-fold). Taken together, the results support the idea that the oestrogenized prostate maintains a very low transcriptional level and protein turnover by affecting canonical signalling pathways and promoting nuclear and nucleolar changes. [source] Does the "New" Immigration Require a "New" Theory of Intergenerational Integration?,INTERNATIONAL MIGRATION REVIEW, Issue 3 2004Hartmut Esser Starting from discussions on the validity of the classical assimilation concept, a general model for the explanation of different structural outcomes of interethnic relations is developed. The core of the model builds on the assumption that different outcomes are the often unintended and situation-logic results of (mis-)investments in and with ethnic and non-ethnic capital. Central initial conditions of the model are group size, social and cultural distances and the availability of social capital. The model specifies the mutual relations between these three constructs. Different variants of intergenerational integration of immigrants can thus be reconstructed as special cases of a general mechanism. [source] Mechanisms of cytochrome P450 substrate oxidation: MiniReviewJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2007F. Peter Guengerich Abstract Cytochrome P450 (P450) enzymes catalyze a variety of oxidation and some reduction reactions, collectively involving thousands of substrates. A general chemical mechanism can be used to rationalize most of the oxidations and involves a perfenyl intermediate (FeO3+) and odd-electron chemistry, i.e. abstraction of a hydrogen atom or electron followed by oxygen rebound and sometimes rearrangement. This general mechanism can explain carbon hydroxylation, heteroatom oxygenation and dealkylation, epoxidation, desaturation, heme destruction, and other reactions. Another approach to understanding catalysis involves analysis of the more general catalytic cycle, including substrate specificity, because complex patterns of cooperativity are observed with several P450s. Some of the complexity is due to slow conformational changes in the proteins that occur on the same timescale as other steps. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:163,168, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20174 [source] Expression of survivin protein in pterygium and relationship with oxidative DNA damageJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6a 2008C. Maxia Abstract Ultraviolet radiation is known to cause oxidative DNA damage and is thought to be a major factor implicated in the pathogenesis of pterygium. Among all the photo-oxidative DNA products, the 8-hydroxydeoxyguanosine (8-OHdG) is regarded a sensitive and stable biomarker for evaluating the degree of DNA damage. The protein p53 is a major cell stress regulator that acts to integrate signals from a wide range of cellular stresses. UV radiation has a carcinogenic effect resulting in DNA damaged cells with loss of normal growth control. This assumption is supported by the association between UV-B exposure and activation of survivin, a member of the inhibitor of apoptosis protein family (IAP), highly up-regulated in almost all types of human malignancy. In this study we demonstrate, for the first time in pterygium, the immunohistochemical presence of survivin, and investigate the correlation between survivin, p53 and 8-OHdG. Our results demonstrate that oxidative stress could lead to a significant activation of survivin expression, suggesting that this might be an important event in the development of pterygium, inducing and supporting a hyperproliferative condition. Survivin expression in pterygium would counteract UV-B-induced apoptosis and would cooperate with loss of p53. The co-operation between survivin and functional loss of p53 might provide a general mechanism for aberrant inhibition of apoptosis that could be responsible for the development of pterygium and its possible progression to neoplasia. [source] Invasion impacts diversity through altered community dynamicsJOURNAL OF ECOLOGY, Issue 6 2005KATHRYN A. YURKONIS Summary 1Invading plant species often alter community structure, composition and, in some instances, reduce local diversity. However, the community dynamics underlying these impacts are relatively unknown. 2Declines in species richness with invasion may occur via displacement of resident species and/or reduction of seedling establishment by the invader. These two mechanisms differ in the demographic stage of the interaction. 3We document turnover dynamics using long-term permanent plot data to assess the mechanism(s) of invasion impacts of four exotic species on a mixed community of native and exotic species. These mechanisms were evaluated at both the neighbourhood (1-m2 plot) and population (individual species) scales. 4During invasion, species richness declined with increasing invader cover for three of the four invaders. All invaders reduced colonization rates, but had no effect on extinction rates at the neighbourhood scale. Populations differed in their susceptibility to invasion impacts, with significant reductions in colonization for 10 of 25 (40%) species and increases in extinction for only 4 of 29 (14%) species. 5At neighbourhood and population scales, influences of invasion on community dynamics were essentially the same for all invaders regardless of life-form. While individual resident species had some increase in extinction probability, community richness impacts were largely driven by colonization limitation. 6The consistency of invasion impacts across life-forms suggests establishment limitation as a general mechanism of invasion impact. This common causal mechanism should be explored in other systems to determine the extent of its generality. [source] The potential role of plant oxygen and sulphide dynamics in die-off events of the tropical seagrass, Thalassia testudinumJOURNAL OF ECOLOGY, Issue 1 2005J. BORUM Summary 1Oxygen and sulphide dynamics were examined, using microelectrode techniques, in meristems and rhizomes of the seagrass Thalassia testudinum at three different sites in Florida Bay, and in the laboratory, to evaluate the potential role of internal oxygen variability and sulphide invasion in episodes of sudden die-off. The sites differed with respect to shoot density and sediment composition, with an active die-off occurring at only one of the sites. 2Meristematic oxygen content followed similar diel patterns at all sites with high oxygen content during the day and hyposaturation relative to the water column during the night. Minimum meristematic oxygen content was recorded around sunrise and varied among sites, with values close to zero at the die-off site. 3Gaseous sulphide was detected within the sediment at all sites but at different concentrations among sites and within the die-off site. Spontaneous invasion of sulphide into Thalassia rhizomes was recorded at low internal oxygen partial pressure during darkness at the die-off site. 4A laboratory experiment showed that the internal oxygen dynamics depended on light availability, and hence plant photosynthesis, and on the oxygen content of the water column controlling passive oxygen diffusion from water column to leaves and below-ground tissues in the dark. 5Sulphide invasion only occurred at low internal oxygen content, and the rate of invasion was highly dependent on the oxygen supply to roots and rhizomes. Sulphide was slowly depleted from the tissues when high oxygen partial pressures were re-established through leaf photosynthesis. Coexistence of sulphide and oxygen in the tissues and the slow rate of sulphide depletion suggest that sulphide reoxidation is not biologically mediated within the tissues of Thalassia. 6Our results support the hypothesis that internal oxygen stress, caused by low water column oxygen content or poor plant performance governed by other environmental factors, allows invasion of sulphide and that the internal plant oxygen and sulphide dynamics potentially are key factors in the episodes of sudden die-off in beds of Thalassia testudinum. Root anoxia followed by sulphide invasion may be a more general mechanism determining the growth and survival of other rooted plants in sulphate-rich aquatic environments. [source] Characterization of covalently inhibited extracellular lipase from Streptomyces rimosus by matrix-assisted laser desorption/ionization time-of-flight and matrix-assisted laser desorption/ionization quadrupole ion trap reflectron time-of-flight mass spectrometry: localization of the active site serine,JOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 12 2004Martin Zehl Abstract A chemical modification approach combined with matrix-assisted laser desorption/ionization (MALDI) mass spectrometry was used to identify the active site serine residue of an extracellular lipase from Streptomyces rimosus R6-554W. The lipase, purified from a high-level overexpressing strain, was covalently modified by incubation with 3,4-dichloroisocoumarin, a general mechanism-based serine protease inhibitor. MALDI time-of-flight (TOF) mass spectrometry was used to probe the nature of the intact inhibitor-modified lipase and to clarify the mechanism of lipase inhibition by 3,4-dichloroisocoumarin. The stoichiometry of the inhibition reaction revealed that specifically one molecule of inhibitor was bound to the lipase. The MALDI matrix 2,6-dihydroxyacetophenone facilitated the formation of highly abundant [M + 2H]2+ ions with good resolution compared to other matrices in a linear TOF instrument. This allowed the detection of two different inhibitor-modified lipase species. Exact localization of the modified amino acid residue was accomplished by tryptic digestion followed by low-energy collision-induced dissociation peptide sequencing of the detected 2-(carboxychloromethyl)benzoylated peptide by means of a MALDI quadrupole ion trap reflectron TOF instrument. The high sequence coverage obtained by this approach allowed the confirmation of the site specificity of the inhibition reaction and the unambiguous identification of the serine at position 10 as the nucleophilic amino acid residue in the active site of the enzyme. This result is in agreement with the previously obtained data from multiple sequence alignment of S. rimosus lipase with different esterases, which indicated that this enzyme exhibits a characteristic Gly-Asp-Ser-(Leu) motif located close to the N-terminus and is harboring the catalytically active serine residue. Therefore, this study experimentally proves the classification of the S. rimosus lipase as GDS(L) lipolytic enzyme. Copyright © 2004 John Wiley & Sons, Ltd. [source] Gill morphometrics in relation to gas transfer and ram ventilation in high-energy demand teleosts: Scombrids and billfishesJOURNAL OF MORPHOLOGY, Issue 1 2010Nicholas C. Wegner Abstract This comparative study of the gill morphometrics in scombrids (tunas, bonitos, and mackerels) and billfishes (marlins, swordfish) examines features of gill design related to high rates of gas transfer and the high-pressure branchial flow associated with fast, continuous swimming. Tunas have the largest relative gill surface areas of any fish group, and although the gill areas of non-tuna scombrids and billfishes are smaller than those of tunas, they are also disproportionally larger than those of most other teleosts. The morphometric features contributing to the large gill surface areas of these high-energy demand teleosts include: 1) a relative increase in the number and length of gill filaments that have, 2) a high lamellar frequency (i.e., the number of lamellae per length of filament), and 3) lamellae that are long and low in profile (height), which allows a greater number of filaments to be tightly packed into the branchial cavity. Augmentation of gill area through these morphometric changes represents a departure from the general mechanism of area enhancement utilized by most teleosts, which lengthen filaments and increase the size of the lamellae. The gill design of scombrids and billfishes reflects the combined requirements for ram ventilation and elevated energetic demands. The high lamellar frequencies and long lamellae increase branchial resistance to water flow which slows and streamlines the ram ventilatory stream. In general, scombrid and billfish gill surface areas correlate with metabolic requirements and this character may serve to predict the energetic demands of fish species for which direct measurement is not possible. The branching of the gill filaments documented for the swordfish in this study appears to increase its gill surface area above that of other billfishes and may allow it to penetrate oxygen-poor waters at depth. J. Morphol. 2010. © 2009 Wiley-Liss, Inc. [source] Effects of Drink-Stress Sequence and Gender on Alcohol Stress Response Dampening in High and Low Anxiety Sensitive DrinkersALCOHOLISM, Issue 3 2007Martin Zack Background: This study tested the appraisal disruption hypothesis of alcohol stress response dampening (SRD) in male and female high or low anxiety sensitive (AS) undergraduates. The hypothesis predicts that alcohol SRD will be greater when drinking occurs before versus after stress exposure. High AS males' predominant social-evaluative concerns further implied that alcohol SRD to a social stressor (i.e., a speech) would be relatively stronger in high AS males than in high AS females. Methods: Male and female (n=90/gender) high and low AS participants (,70th; ,30th percentile on Anxiety Sensitivity Index-Revised) were matched on drinking habits and randomly assigned to 1 of 9 experimental cells. Drink type,alcohol (0.7 g/kg males; 0.63 g/kg females), placebo, soda,was fully crossed with stress condition,drink before stress (DBS), drink after stress (DAS), and no stress control (NSC). Stress was induced by telling participants they would be required to make a self-revealing speech. Stress response dampening was assessed for state anxiety on the Spielberger scale and Stroop interference to threat-related words. Subjective desire for alcohol was also assessed. Results: Relative to placebo, alcohol (peak blood alcohol concentration, 0.064%) reliably reduced state anxiety in high AS but not in low AS participants. Alcohol decreased STAI scores and Stroop interference to social threat words significantly more in the DBS than the DAS condition in high AS males; high AS females displayed the exact opposite pattern of effects. In contrast to other participants, high AS males also reported relatively strong desire scores under alcohol. Conclusions: Overall, the results do not support the appraisal disruption hypothesis as a general mechanism of alcohol SRD in undergraduate drinkers. The findings for high AS males do support the hypothesis, while the opposing profile for high AS females implies that the nature of the stressor (i.e., social challenge) may contribute to gender differences in alcohol SRD in high AS individuals. [source] Cell death: regulation by the Bcl-2 protein familyPSYCHOGERIATRICS, Issue 2006Yoshihide TSUJIMOTO Abstract An increase in mitochondrial membrane permeability is central to cell death including apoptosis and necrosis. During apoptosis, permeabilization of outer mitochondrial membrane leads to the release of several apoptogenic factors, such as cytochrome c and Smac/Diablo, into the cytoplasm that activate downstream death programs, including apoptotic proteases called caspases, although the detailed mechanism of outer mitochondrial membrane permeabilization remains elusive. Although the mitochondrial membrane permeability transition (MPT), resulting in ,, loss, mitochondrial swelling and rupture of the outer membrane has initially been proposed as a general mechanism for apoptotic permeabilization of outer mitochondrial membrane, the recent studies with cyclophilin D-deficient mice indicate that MPT regulates some forms of necrotic death, but not apoptotic death, and that MPT is involved in ischemia,reperfusion injury in heart and brain. Anti-apoptotic proteins, Bcl-2 and Bcl-xL, efficiently block not only apoptotic mitochondrial permeabilization but also MPT. The present paper focuses on the mechanisms by which Bcl-2 family members control the permeability of mitochondrial membrane during apoptosis and necrosis. [source] Intersubsystem chemical bonds in the misfit layer compounds (LaS)1.13TaS2 and (LaS)1.14NbS2ACTA CRYSTALLOGRAPHICA SECTION B, Issue 2 2002Andreas Jobst The modulated structures of incommensurate composite crystals (La0.912S)1.13TaS2 at room temperature and of (La0.949S)1.14NbS2 at T = 115,K are refined against high-resolution X-ray data. The compounds are isostructural with superspace group F,m2m(,,0,0)00s. For (LaS)1.13TaS2, lattice parameters of the first subsystem TaS2 were obtained as a = 3.2922,(1), b = 5.7776,(2) and c = 23.013,(2),Å. For the second subsystem LaS, the same b and c parameters were found, but a = 5.8090,(8),Å. Refinements led to a final structure model with R = 0.036 for 4767 observed unique reflections (R = 0.023 for 2147 main reflections, R = 0.099 for 1554 first-order satellites and R = 0.112 for 1042 second-order satellites). The final model includes modulation parameters up to the second-order harmonics for the displacements of the atoms, for the occupational parameters and for the temperature parameters. A clear correlation is found between the relative positions of the subsystems, the displacement modulation, the occupational modulation and the modulation of the temperature parameters. The analysis shows that the variations in environments are resolved by correlated variations in the temperature factors. For (LaS)1.14NbS2, lattice parameters at T = 115,K of the NbS2 subsystem were obtained as a = 3.3065,(4), b = 5.7960,(5) and c = 22.956,(3),Å. For the LaS subsystem, the same values for b and c were obtained, but a = 5.7983,(7),Å. Refinements led to a final structure model with R = 0.048 for 5909 observed unique reflections (R = 0.034 for 2528 main reflections, R = 0.092 for 2171 first-order satellites and R = 0.113 for 1103 second-order satellites). The final structure model is similar to that of (LaS)1.13TaS2. In particular, it is found that the values of the modulation parameters are almost equal and it is concluded that the modulations are independent of the temperature and the replacement of Ta with Nb, and thus represent a general mechanism of resolving the strain between the mutually incommensurate layers. [source] Homogeneity of active demyelinating lesions in established multiple sclerosisANNALS OF NEUROLOGY, Issue 1 2008Esther C. W. Breij PhD Objective Four different patterns of demyelination have been described in active demyelinating lesions of multiple sclerosis (MS) patients that were biopsied shortly after disease onset. These patterns were suggested to represent heterogeneity of the underlying pathogenesis. The aim of this study was to determine whether lesion heterogeneity also exists in an unselected collection of autopsy material from patients with established MS. Methods All MS brain tissue available in the VU Medical Center was assessed for the presence of active demyelinating lesions using magnetic resonance imaging,guided sampling and immunohistochemistry. Tissue blocks containing active demyelinating lesions were evaluated for the presence of complement and antibody deposition, oligodendrocyte apoptosis, differential loss of myelin proteins, and hypoxia-like damage using histology, immunohistochemistry, and confocal microscopy. Blocks with active demyelinating lesions were compared with blocks with active (nondemyelinating) and inactive lesions. Results Complement and antibodies were consistently associated with macrophages in areas of active demyelination. Preferential loss of myelin proteins, extensive hypoxia-like damage, and oligodendrocyte apoptosis were absent or rare. This pattern was observed in all tissue blocks containing active demyelinating lesions; lesion heterogeneity between patients was not found. Interpretation The immunopathological appearance of active demyelinating lesions in established MS is uniform. Initial heterogeneity of demyelinating lesions in the earliest phase of MS lesion formation may disappear over time as different pathways converge in one general mechanism of demyelination. Consistent presence of complement, antibodies, and Fc, receptors in phagocytic macrophages suggests that antibody- and complement-mediated myelin phagocytosis is the dominant mechanism of demyelination in established MS. Ann Neurol 2008;63:16,25 [source] Modulation of activity by Arg407: structure of a fungal ,-1,2-mannosidase in complex with a substrate analogueACTA CRYSTALLOGRAPHICA SECTION D, Issue 3 2008Yuri D. Lobsanov Class I ,-mannosidases (glycoside hydrolase family GH47) play key roles in the maturation of N-glycans and the ER-associated degradation of unfolded glycoproteins. The 1.95,Å resolution structure of a fungal ,-1,2-mannosidase in complex with the substrate analogue methyl-,- d -lyxopyranosyl-(1,,2)-,- d -mannopyranoside (LM) shows the intact disaccharide spanning the ,1/+1 subsites, with the d -lyxoside ring in the ,1 subsite in the 1C4 chair conformation, and provides insight into the mechanism of catalysis. The absence of the C5, hydroxymethyl group on the d -lyxoside moiety results in the side chain of Arg407 adopting two alternative conformations: the minor one interacting with Asp375 and the major one interacting with both the d -lyxoside and the catalytic base Glu409, thus disrupting its function. Chemical modification of Asp375 has previously been shown to inactivate the enzyme. Taken together, the data suggest that Arg407, which belongs to the conserved sequence motif RPExxE, may act to modulate the activity of the enzyme. The proposed mechanism for modulating the activity is potentially a general mechanism for this superfamily. [source] The effect of ZD1839 (IressaTM), an epidermal growth factor receptor tyrosine kinase inhibitor, in combination with cisplatin, on apoptosis in SCC-15 cellsCELL PROLIFERATION, Issue 2 2005A. Al-Hazzaa High expression of the epidermal growth factor receptor has been implicated in the development of squamous cell carcinomas of head and neck. ZD1839 (,Iressa') is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor that blocks signal transduction pathways implicated in proliferation and survival of cancer cells, and other host-dependent processes promoting cancer growth. Here, growth arrest was observed with 3.64 µm ZD1839. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (sMTT) viability assay revealed a significant decrease (P < 0.001) in the percentage of surviving cells upon treatment with ZD1839 and cisplatin compared with cisplatin or ZD1839 on their own. Combined therapy of 3.64 µm ZD1839 for 24 h, prior to administration of 100 µm cisplatin, significantly (P < 0.001) and additively increased the cytotoxicity effect of cisplatin. p53-independent apoptosis was seen with cisplatin treatment, a novel finding. These data support the use of ZD1839 in anti-cancer therapy, and particularly in combination therapy. Cisplatin may induce p53-independent apoptosis. Over-expression of Bcl-2 in head and neck squamous cell carcinoma tumour cell lines is unlikely to be a general mechanism to protect these cells from apoptosis. [source] Allosteric Regulation of ProteasesCHEMBIOCHEM, Issue 18 2008Patrick Hauske Abstract Allostery is a basic principle of control of enzymatic activities based on the interaction of a protein or small molecule at a site distinct from an enzyme's active center. Allosteric modulators represent an alternative approach to the design and synthesis of small-molecule activators or inhibitors of proteases and are therefore of wide interest for medicinal chemistry. The structural bases of some proteinaceous and small-molecule allosteric protease regulators have already been elucidated, indicating a general mechanism that might be exploitable for future rational design of small-molecule effectors. [source] Are there general mechanisms of animal home range behaviour?ECOLOGY LETTERS, Issue 6 2008A review, prospects for future research Abstract Home range behaviour is a common pattern of space use, having fundamental consequences for ecological processes. However, a general mechanistic explanation is still lacking. Research is split into three separate areas of inquiry , movement models based on random walks, individual-based models based on optimal foraging theory, and a statistical modelling approach , which have developed without much productive contact. Here we review recent advances in modelling home range behaviour, focusing particularly on the problem of identifying mechanisms that lead to the emergence of stable home ranges from unbounded movement paths. We discuss the issue of spatiotemporal scale, which is rarely considered in modelling studies, as well as highlighting the need to consider more closely the dynamical nature of home ranges. Recent methodological and theoretical advances may soon lead to a unified approach, however, conceptually unifying our understanding of linkages among home range behaviour and ecological or evolutionary processes. [source] Ample genetic variation but no evidence for genotype specificity in an all-parthenogenetic host,parasitoid interactionJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 3 2010C. SANDROCK Abstract Antagonistic coevolution between hosts and parasites can result in negative frequency-dependent selection and may thus be an important mechanism maintaining genetic variation in populations. Negative frequency-dependence emerges readily if interactions between hosts and parasites are genotype-specific such that no host genotype is most resistant to all parasite genotypes, and no parasite genotype is most infective on all hosts. Although there is increasing evidence for genotype specificity in interactions between hosts and pathogens or microparasites, the picture is less clear for insect host,parasitoid interactions. Here, we addressed this question in the black bean aphid (Aphis fabae) and its most important parasitoid Lysiphlebus fabarum. Because both antagonists are capable of parthenogenetic reproduction, this system allows for powerful tests of genotype × genotype interactions. Our test consisted of exposing multiple host clones to different parthenogenetic lines of parasitoids in all combinations, and this experiment was repeated with animals from four different sites. All aphids were free of endosymbiotic bacteria known to increase resistance to parasitoids. We observed ample genetic variation for host resistance and parasitoid infectivity, but there was no significant host clone × parasitoid line interaction, and this result was consistent across the four sites. Thus, there is no evidence for genotype specificity in the interaction between A. fabae and L. fabarum, suggesting that the observed variation is based on rather general mechanisms of defence and attack. [source] Toward a transnational history of the social sciencesJOURNAL OF THE HISTORY OF THE BEHAVIORAL SCIENCES, Issue 2 2008Johan Heilbron Historical accounts of the social sciences have too often accepted local or national institu-tions as a self-evident framework of analysis, instead of considering them as being embed-ded in transnational relations of various kinds. Evolving patterns of transnational mobility and exchange cut through the neat distinction between the local, the national, and the inter-national, and thus represent an essential component in the dynamics of the social sciences, as well as a fruitful perspective for rethinking their historical development. In this pro-grammatic outline, it is argued that a transnational history of the social sciences may be fruitfully understood on the basis of three general mechanisms, which have structured the transnational flows of people and ideas in decisive ways: (a) the functioning of international scholarly institutions, (b) the transnational mobility of scholars, and (c) the politics of trans-national exchange of nonacademic institutions. The article subsequently examines and illustrates each of these mechanisms. © 2008 Wiley Periodicals, Inc. [source] How epithelial cells detect danger: aiding the immune responseALLERGY, Issue 9 2008A. B. Vroling The epithelial layer occupies a strategic important location between an organisms' interior and exterior environment. Although as such it forms a physical barrier between both environments, it became clear that the role of the epithelium extends far beyond this rather passive role. Through specialized receptors and other more general mechanisms, the epithelial layer is not only able to sense changes in its environment but also to actively respond to these changes. These responses allow the epithelium to contribute to wound and tissue repair, to the defense against micro-organisms, and to the control and regulation of the locale immune response. In this review, we focus on signals acting on epithelium from the exterior environment, how these signals are processed and identify research challenges. [source] Generalist Genes: Genetic Links Between Brain, Mind, and EducationMIND, BRAIN, AND EDUCATION, Issue 1 2007Robert Plomin ABSTRACT, Genetics contributes importantly to learning abilities and disabilities,not just to reading, the target of most genetic research, but also to mathematics and other academic areas as well. One of the most important recent findings from quantitative genetic research such as twin studies is that the same set of genes is largely responsible for genetic influence across these domains. We call these "generalist genes" to highlight their pervasive influence. In other words, most genes found to be associated with a particular learning ability or disability (such as reading) will also be associated with other learning abilities and disabilities (such as mathematics). Moreover, some generalist genes for learning abilities and disabilities are even more general in their effect, encompassing other cognitive abilities such as memory and spatial ability. When these generalist genes are identified, they will greatly accelerate research on general mechanisms at all levels of analysis from genes to brain to behavior. [source] Anesthetic considerations for the pediatric oncology patient , part 1: a review of antitumor therapyPEDIATRIC ANESTHESIA, Issue 4 2010GREGORY J. LATHAM MD Abstract The anesthesiologist who cares for children with cancer or for survivors of childhood cancer should possess a basic understanding of cancer treatment. While this is an ever-changing field, a basic knowledge of chemotherapeutic drugs, radiation therapy, and the toxicities of each is necessary to prepare a safe anesthetic plan. Such an understanding also assists the anesthesiologist as the perioperative specialist for these children in consultation with the surgeon and oncologist. This article, which is the first of a three-part review series, will review current principles of cancer therapy and the general mechanisms of toxicity to the child. Although this article is not intended to comprehensively review the fundamentals of chemotherapy and radiation therapy, the consequences of anticancer therapy that impact perioperative care and decision making are presented for the anesthesiologist. [source] Imprinted genes and human disease,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2010Rosanna Weksberg Abstract This issue of Seminars of Medical Genetics features a series of articles on human disorders caused by the dysregulation of imprinted genes. At the outset, there is a review of the general mechanisms by which genomic imprinting is normally regulated followed by an exploration of the clinical and molecular aspects of human imprinting disorders. As we enter an era of bioinformatics and genome-wide analyses with increasing access to high density microarrays and next generation sequencing, it is becoming apparent that the concept of a single mutation or epimutation leading to a disease is outdated. The role of the clinician will become increasingly important, in concert with these molecular advances, in terms of evaluating phenotypic variation to further our understanding of imprinting disorders. Such investigations will benefit children and families as we become better able to define recurrence risk, predict phenotype, and tailor medical management. © 2010 Wiley-Liss, Inc. [source] Induction of type I interferons by bacteriaCELLULAR MICROBIOLOGY, Issue 7 2010Kathryn M. Monroe Summary Type I interferons (IFNs) are secreted cytokines that orchestrate diverse immune responses to infection. Although typically considered to be most important in the response to viruses, type I IFNs are also induced by most, if not all, bacterial pathogens. Although diverse mechanisms have been described, bacterial induction of type I IFNs occurs upon stimulation of two main pathways: (i) Toll-like receptor (TLR) recognition of bacterial molecules such as lipopolysaccharide (LPS); (ii) TLR-independent recognition of molecules delivered to the host cell cytosol. Cytosolic responses can be activated by two general mechanisms. First, viable bacteria can secrete stimulatory ligands into the cytosol via specialized bacterial secretion systems. Second, ligands can be released from bacteria that lyse or are degraded. The bacterial ligands that induce the cytosolic pathways remain uncertain in many cases, but appear to include various nucleic acids. In this review, we discuss recent advances in our understanding of how bacteria induce type I interferons and the roles type I IFNs play in host immunity. [source] | ||||||||||||||||||||||