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Multiple Pathways (multiple + pathway)
Selected AbstractsMultiple Pathways for the Irreversible Inhibition of Steroid Sulfatase with Quinone Methide-Generating Suicide InhibitorsCHEMBIOCHEM, Issue 9 2009Vanessa Ahmed Abstract Unexpected inhibition: 2- and 4-mono- and difluoromethyl estrone sulfate derivatives are suicide inhibitors of steroid sulfatase (STS). Kinetic studies suggest that inhibition by the monofluoro derivatives is a result of a quinone methide intermediate that reacts with active-site nucleophiles, whereas the main inhibition pathway of the 4-difluoromethyl derivative is a result of decomposition of the initial quinone methide to an aldehyde that acts as potent, almost irreversible inhibitor. [source] Multiple pathways for invasion of anurans on a Pacific islandDIVERSITY AND DISTRIBUTIONS, Issue 5 2007Michelle T. Christy ABSTRACT Since 1937, thirteen species of non-indigenous anurans have made their way to Guam. Of these, at least six have established breeding populations. Various pathways led to the introduction of these species to the island. The only anuran intentionally introduced was Chaunus marinus (formerly Bufo marinus), which was brought to Guam as a biocontrol agent. Kaloula picta, K. pulchra, Polypedates leucomystax, and probably Litoria fallax arrived as stowaways via maritime or air-transport vessels. Eleutherodactylus coqui and Euhyas (formerly Eleutherodactylus) planirostris appear to have entered Guam through the horticultural trade. Specimens of Pseudacris regilla were found among agricultural products and Christmas trees. Five species have been transported to Guam via the aquacultural trade. The importation of tilapia, milkfish, and white shrimp from China, Hong Kong, Taiwan, and the Philippines was associated with the introduction to Guam of Fejervarya cancrivora, F. limnocharis sensu lato, Microhyla pulchra, Polypedates megacephalus, and Sylvirana guentheri (formerly Rana guentheri). Presently, no quarantine or containment guidelines have been established for Guam's aquacultural industry. [source] Multiple pathways in the FGF signaling network are frequently deregulated by gene amplification in oral dysplasiasINTERNATIONAL JOURNAL OF CANCER, Issue 9 2009Ivy F.L. Tsui Abstract Genetic alteration in oral premalignant lesions (OPLs), the precursors of oral squamous cell carcinomas (OSCCs), may represent key changes in disease initiation and development. We ask if DNA amplification occurs at this early stage of cancer development and which oncogenic pathways are disrupted in OPLs. Here, we evaluated 50 high-grade dysplasias and low-grade dysplasias that later progressed to cancer for gene dosage aberrations using tiling-path DNA microarrays. Early occurrences of DNA amplification and homozygous deletion were frequently detected, with 40% (20/50) of these early lesions exhibiting such features. Expression for 88 genes in 7 recurrent amplicons were evaluated in 5 independent head and neck cancer datasets, with 40 candidates found to be overexpressed relative to normal tissues. These genes were significantly enriched in the canonical ERK/MAPK, FGF, p53, PTEN and PI3K/AKT signaling pathways (p = 8.95 × 10,3 to 3.18 × 10,2). These identified pathways share interactions in one signaling network, and amplification-mediated deregulation of this network was found in 30.0% of these preinvasive lesions. No such alterations were found in 14 low-grade dysplasias that did not progress, whereas 43.5% (10/23) of OSCCs were found to have altered genes within the pathways with DNA amplification. Multitarget FISH showed that amplification of EGFR and CCND1 can coexist in single cells of an oral dysplasia, suggesting the dependence on multiple oncogenes for OPL progression. Taken together, these findings identify a critical biological network that is frequently disrupted in high-risk OPLs, with different specific genes disrupted in different individuals. © 2009 UICC [source] Multiple pathways for woody plant establishment on floodplains at local to regional scalesJOURNAL OF ECOLOGY, Issue 2 2003David J. Cooper Summary 1The structure and functioning of riverine ecosystems is dependent upon regional setting and the interplay of hydrologic regime and geomorphologic processes. We used a retrospective analysis to study recruitment along broad, alluvial valley segments (parks) and canyon segments of the unregulated Yampa River and the regulated Green River in the upper Colorado River basin, USA. We precisely aged 811 individuals of Populus deltoides ssp. wislizenii (native) and Tamarix ramosissima (exotic) from 182 wooded patches and determined the elevation and character of the germination surface for each. We used logistic regression to relate recruitment events (presence or absence of cohort) to five flow and two weather parameters. 2Woody plant establishment occurred via multiple pathways at patch, reach and segment scales. Recruitment occurred through establishment on (1) vertically accreting bars in the unregulated alluvial valley, (2) high alluvial floodplain surfaces during rare large flood events, (3) vertically accreting channel margin deposits in canyon pools and eddies, (4) vertically accreting intermittent/abandoned channels, (5) low elevation gravel bars and debris fans in canyons during multi-year droughts, and (6) bars and channels formed prior to flow regulation on the dammed river during controlled flood events. 3The Yampa River's peak flow was rarely included in models estimating the likelihood that recruitment would occur in any year. Flow variability and the interannual pattern of flows, rather than individual large floods, control most establishment. 4Regulation of the Green River flow since 1962 has had different effects on woody vegetation recruitment in canyons and valleys. The current regime mimics drought in a canyon setting, accelerating Tamarix invasion whereas in valleys the ongoing geomorphic adjustment of the channel, combined with reduced flow variability, has nearly eliminated Populus establishment. 5A single year's flow or a particular pattern of flows over a sequence of years, whether natural or man-made, produces different recruitment opportunities in alluvial and canyon reaches, in diverse landforms within a particular river reach, and for Populus and Tamarix. The design of flows to restore riparian ecosystems must consider these multiple pathways and adjust the seasonal timing, magnitude and interannual frequency of flows to match the desired outcome. [source] Multiple pathways of maternal effects in black-headed gull eggs: constraint and adaptive compensatory adjustmentJOURNAL OF EVOLUTIONARY BIOLOGY, Issue 4 2006T. G. G. GROOTHUIS Abstract We investigated in the black-headed gull whether female deposition of antioxidants and immunoglobulins (enhancing early immune function), and testosterone (suppressing immune function and increasing early competitive skills) correlate suggesting that evolution has favoured the mutual adjustment of different pathways for maternal effects. We also took egg mass, the position of the egg in the laying sequence and offspring sex into account, as these affect offspring survival. Yolk antioxidant and immunoglobulin concentrations decreased across the laying order, while yolk testosterone concentrations increased. This may substantially handicap the immune defence of last-hatched chicks. The decrease in antioxidant levels was greater when mothers had a low body mass and when the increase in testosterone concentrations was relatively large. This suggests that female black-headed gulls are constrained in the deposition of antioxidants in last-laid eggs and compensate for this by enhanced testosterone deposition. The latter may be adaptive since it re-allocates the chick's investment from costly immune function to growth and competitive skills, necessary to overcome the consequences of hatching late from an egg of reduced quality. [source] Multiple pathways to adulthood: Expanding the learning options for urban youthNEW DIRECTIONS FOR YOUTH DEVELOPMENT, Issue 97 2003Adria Steinberg Some learning environments show particular promise of creating pathways to postsecondary education, careers, and engaged citizenship for urban young adults from ages fifteen to twenty-four. [source] Staying alive , naïve CD4+ T cell homeostasisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007Jared F. Purton Abstract The immune system must maintain a broad repertoire of naïve T cells in order to respond to the diverse range of pathogens that it will encounter over the course of a lifetime. Although it is known that contact with IL-7 is crucial for the survival of naïve T cells, the precise intracellular signals that mediate its effects remain obscure. An article in this issue of the European Journal of Immunology has found that IL-7 requires the coordinated action of multiple pathways to maintain naïve CD4+ T cells. See accompanying article: http://dx.doi.org/10.1002/eji.200737234 [source] Protein Kinase C Regulation of Rat Jejunal Transport Systems: Mechanisms Involved in Lactate MovementEXPERIMENTAL PHYSIOLOGY, Issue 6 2002Marisa Tosco We examined whether protein kinase C (PKC) modulates the transport systems involved in lactate movements across the plasma membranes of rat jejunum. In vitro phosphorylated membrane vesicles were used to perform uptake studies, the results of which suggested that PKC activation exerts an inhibitory effect on basolateral H+ -lactate symport, as well as on apical Na+ -glucose cotransport. The specificity of the response to PKC was confirmed by using staurosporine, chelerythrine or 4-,-PMA. Experiments performed using the whole tissue incubated in vitro confirmed the reduction of lactate transport elicited by PKC and gave evidence for an associated inhibition of fluid transport. Na+,K+ -ATPase activity seems to be unaffected by the kinase and inhibited by Ca2+. Taken together, our results suggest that the overall action of PKC results from the simultananeous modulation of multiple pathways, targeted to a reduction of both lactate and bicarbonate transports without altering cell pH homeostasis. [source] Temporal lobe grey matter volume in schizophrenia is associated with a genetic polymorphism influencing glycogen synthase kinase 3-, activityGENES, BRAIN AND BEHAVIOR, Issue 4 2010F. Benedetti At the crossroad of multiple pathways regulating trophism and metabolism, glycogen synthase kinase (GSK)3 is considered a key factor in influencing the susceptibility of neurons to harmful stimuli (neuronal resilience) and is a target for several psychiatric drugs that directly inhibit it or increase its inhibitory phosphorylation. Inhibition of GSK3 prevents apoptosis and could protect against the neuropathological processes associated with psychiatric disorders. A GSK3- ,promoter single-nucleotide polymorphism (rs334558) influences transcriptional strength, and the less active form was associated with less detrimental clinical features of mood disorders. Here we studied the effect of rs334558 on grey matter volumes (voxel-based morphometry) of 57 patients affected by chronic schizophrenia. Carriers of the less active C allele variant showed significantly higher brain volumes in an area encompassing posterior regions of right middle and superior temporal gyrus, within the boundaries of Brodmann area 21. The temporal lobe is the brain parenchymal region with the most consistently documented morphometric abnormalities in schizophrenia, and neuropathological processes in these regions develop soon at the beginning of the illness. These results support the interest for GSK3- ,as a factor affecting neuropathology in major behavioural disorders, such as schizophrenia, and thus as a possible target for treatment. [source] Oncogenetic tree model of somatic mutations and DNA methylation in colon tumorsGENES, CHROMOSOMES AND CANCER, Issue 1 2009Carol Sweeney Our understanding of somatic alterations in colon cancer has evolved from a concept of a series of events taking place in a single sequence to a recognition of multiple pathways. An oncogenetic tree is a model intended to describe the pathways and sequence of somatic alterations in carcinogenesis without assuming that tumors will fall in mutually exclusive categories. We applied this model to data on colon tumor somatic alterations. An oncogenetic tree model was built using data on mutations of TP53, KRAS2, APC, and BRAF genes, methylation at CpG sites of MLH1 and TP16 genes, methylation in tumor (MINT) markers, and microsatellite instability (MSI) for 971 colon tumors from a population-based series. Oncogenetic tree analysis resulted in a reproducible tree with three branches. The model represents methylation of MINT markers as initiating a branch and predisposing to MSI, methylation of MHL1 and TP16, and BRAF mutation. APC mutation is the first alteration in an independent branch and is followed by TP53 mutation. KRAS2 mutation was placed a third independent branch, implying that it neither depends on, nor predisposes to, the other alterations. Individual tumors were observed to have alteration patterns representing every combination of one, two, or all three branches. The oncogenetic tree model assumptions are appropriate for the observed heterogeneity of colon tumors, and the model produces a useful visual schematic of the sequence of events in pathways of colon carcinogenesis. © 2008 Wiley-Liss, Inc. [source] Caspases and T lymphocytes: a flip of the coin?IMMUNOLOGICAL REVIEWS, Issue 1 2003Saquib Lakhani Summary:, In this review, we consider the role caspases play in cell death downstream of death receptors and cell intrinsic death mechanisms. In particular, we focus on these mechanisms in antigen-induced cell death, a mechanism which regulates the number of surviving T cells at the end of an immune response. The relative role of the apoptosome as an amplifier rather than an initiator of apoptosis is considered. Several factors that regulate the susceptibility to activation-induced cell death are considered. These factors emanate from the stimulation of the T-cell receptors and include multiple pathways. Recent work has shown that death receptor signaling can play an interesting role in cell proliferation in both humans and animals. These recent findings are discussed in the light of models of death receptor signaling. [source] Multiple-Well, multiple-path unimolecular reaction systems.INTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 4 2001Vibrationally excited 2-methylhexyl radicals formed by shock wave activation or by chemical activation can isomerize by multiple pathways to form any of six stable isomers, can fragment by multiple CH and CC bond fission pathways, and can be collisionally stabilized. Master equation simulations of chemical activation and of shock wave activation are used to explore the generic behavior of this complicated coupled system. Selecting the argon pressure in chemical activation systems that produce the 2-methyl-1-hexyl radical isomer (1) can control the yield of specific isomers. Shock heating of 1 also shows a highly regular sequence of isomer formation. This regular behavior is because the first isomerization steps are faster than subsequent steps. Other radical isomers, such as 2-methyl-3-hexyl (3), do not show such regular behavior, because the first isomerization step is slower than subsequent steps. Incubation and unimolecular rate-constant fall-off are observed in the shock wave simulations. The unimolecular rate-constant fall-off for the coupled system produces low-pressure limiting rate constants proportional to [M]n, where n can be greater than unity. The fact that n can be greater than unity is a natural feature of multichannel coupled unimolecular reaction systems, but detection of the effect in experiments may be very demanding. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 246,261, 2001 [source] Hepatocyte progenitors in man and in rodents , multiple pathways, multiple candidatesINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2005Joanna Laurson Summary In severe injury, liver-cell progenitors may play a role in recovery, proliferating, and subsequently differentiating into mature liver cells. Identifying these progenitors has major therapeutic potential for ex vivo pharmaceutical testing, bioartificial liver support, tissue engineering and gene therapy protocols. Potential liver-cell progenitors have been identified from bone marrow, peripheral blood, cord blood, foetal liver, adult liver and embryonic stem cells. Differences and similarities are found among cells isolated from rodents and humans. This review will discuss identifying markers and differentiation potential in in vitro and in vivo models of these putative progenitors in both humans and rodents. [source] Multiple pathways for woody plant establishment on floodplains at local to regional scalesJOURNAL OF ECOLOGY, Issue 2 2003David J. Cooper Summary 1The structure and functioning of riverine ecosystems is dependent upon regional setting and the interplay of hydrologic regime and geomorphologic processes. We used a retrospective analysis to study recruitment along broad, alluvial valley segments (parks) and canyon segments of the unregulated Yampa River and the regulated Green River in the upper Colorado River basin, USA. We precisely aged 811 individuals of Populus deltoides ssp. wislizenii (native) and Tamarix ramosissima (exotic) from 182 wooded patches and determined the elevation and character of the germination surface for each. We used logistic regression to relate recruitment events (presence or absence of cohort) to five flow and two weather parameters. 2Woody plant establishment occurred via multiple pathways at patch, reach and segment scales. Recruitment occurred through establishment on (1) vertically accreting bars in the unregulated alluvial valley, (2) high alluvial floodplain surfaces during rare large flood events, (3) vertically accreting channel margin deposits in canyon pools and eddies, (4) vertically accreting intermittent/abandoned channels, (5) low elevation gravel bars and debris fans in canyons during multi-year droughts, and (6) bars and channels formed prior to flow regulation on the dammed river during controlled flood events. 3The Yampa River's peak flow was rarely included in models estimating the likelihood that recruitment would occur in any year. Flow variability and the interannual pattern of flows, rather than individual large floods, control most establishment. 4Regulation of the Green River flow since 1962 has had different effects on woody vegetation recruitment in canyons and valleys. The current regime mimics drought in a canyon setting, accelerating Tamarix invasion whereas in valleys the ongoing geomorphic adjustment of the channel, combined with reduced flow variability, has nearly eliminated Populus establishment. 5A single year's flow or a particular pattern of flows over a sequence of years, whether natural or man-made, produces different recruitment opportunities in alluvial and canyon reaches, in diverse landforms within a particular river reach, and for Populus and Tamarix. The design of flows to restore riparian ecosystems must consider these multiple pathways and adjust the seasonal timing, magnitude and interannual frequency of flows to match the desired outcome. [source] Functional genomic approach to identify novel genes involved in the regulation of oxidative stress resistance and animal lifespanAGING CELL, Issue 4 2007Yongsoon Kim Summary Genetic studies in many organisms suggest that an increased animal lifespan phenotype is often accompanied by enhanced resistance toward reactive oxygen species (ROS). In Caenorhabditis elegans, mutations in daf-2, which encode an insulin/insulin-like growth factor 1 receptor-like molecule, lead to an extended animal lifespan and increased resistance to ROS. We have optimized an assay to monitor ROS resistance in worms using the ROS-generating chemical paraquat. We have employed this assay to screen the RNAi library along chromosomes III and IV for genes that, when silenced, confer paraquat resistance. The positive RNAi clones were subsequently screened for a lifespan extension phenotype. Using this approach, we have identified 84 genes that, when inactivated by RNAi, lead to significant increases in animal lifespan. Among the 84 genes, 29 were found to act in a manner dependent on daf-16. DAF-16, a forkhead transcription factor, is known to integrate signals from multiple pathways, including the daf-2 pathway, to regulate animal lifespan. Most of the 84 genes have not been previously linked to aging, and potentially participate in important cellular processes such as signal transduction, cell,cell interaction, gene expression, protein degradation, and energy metabolism. Our screen has also identified a group of genes that potentially function in a nutrient-sensing pathway to regulate lifespan in C. elegans. Our study provides a novel approach to identify genes involved in the regulation of aging. [source] What does the male function hypothesis claim?JOURNAL OF EVOLUTIONARY BIOLOGY, Issue 5 2000Burd Paternal, rather than maternal, fitness consequences of reproductive traits are the lynchpin in many hypotheses about reproductive evolution in hermaphroditic angiosperms. These hypotheses often differ in their predictions, so that supporting or contradictory evidence for one hypothesis may not reflect similarly on another, even though both may be referred to as ,the male function hypothesis'. We provide graphical representations of four male function hypotheses from the recent literature in order to highlight their differences. We offer and explain two recommendations to reduce ambiguity in terminology: (1) male function hypotheses should address the evolution of excess flowers per se, rather than total flower number, which is usually highly plastic in modular organisms with open growth form; and (2) attention must be given to whole plant fitness, rather than fitness per flower or per inflorescence. In empirical studies, we recommend the use of path analysis to dissect the multiple pathways (through both male and female function) by which selection may act on excess flower number. [source] Lipophilic regulator of a developmental switch in Caenorhabditis elegansAGING CELL, Issue 6 2004Matthew S. Gill In Caenorhabditis elegans, the decision to develop into a reproductive adult or arrest as a dauer larva is influenced by multiple pathways including insulin-like and transforming growth factor , (TGF,)-like signalling pathways. It has been proposed that lipophilic hormones act downstream of these pathways to regulate dauer formation. One likely target for such a hormone is DAF-12, an orphan nuclear hormone receptor that mediates these developmental decisions and also influences adult lifespan. In order to find lipophilic hormones we have generated lipophilic extracts from mass cultures of C. elegans and shown that they rescue the dauer constitutive phenotype of class 1 daf-2 insulin signalling mutants and the TGF, signalling mutant daf-7. These extracts are also able to rescue the lethal dauer phenotype of daf-9 mutants, which lack a P450 steroid hydroxylase thought to be involved in the synthesis of the DAF-12 ligand; extracts, however, have no effect on a DAF-12 ligand binding domain mutant that is predicted to be ligand insensitive. The production of this hormone appears to be DAF-9 dependent as extracts from a daf-9;daf-12 double mutant do not exhibit this activity. Preliminary fractionation of the lipophilic extracts shows that the activity is hydrophobic with some polar properties, consistent with a small lipophilic hormone. We propose that the dauer rescuing activity is a hormone synthesized by DAF-9 that acts through DAF-12. [source] Parents' Affect, Adolescent Cognitive Representations, and Adolescent Social DevelopmentJOURNAL OF MARRIAGE AND FAMILY, Issue 3 2000Blair Paley Prior research regarding the role of parent-child relationships in children's social development generally has been limited to concurrent or short-term longitudinal data and has focused primarily on mothers' influence in the early or middle childhood years. Using a multimethod, multiinformant design, the present study extends previous findings by examining whether maternal and paternal affect predicted adolescent social behavior and peer acceptance 2 years later. Both maternal and paternal affect had significant direct and indirect effects (via adolescent cognitive representations of parents) on adolescent negative social behavior as reported by siblings, which in turn predicted decreased peer acceptance as rated by teachers. Findings suggest that both mothers and fathers shape adolescent social development and attest to the importance of exploring multiple pathways that may account for continuity in parent-child and peer relationships. [source] Steroid-induced sexual differentiation of the developing brain: multiple pathways, one goalJOURNAL OF NEUROCHEMISTRY, Issue 5 2008Jaclyn M. Schwarz Abstract Hormone exposure, including testosterone and its metabolite estradiol, induces a myriad of effects during a critical period of brain development that are necessary for brain sexual differentiation. Nuclear volume, neuronal morphology, and astrocyte complexity are examples of the wide range of effects by which testosterone and estradiol can induce permanent changes in the function of neurons for the purpose of reproduction in adulthood. This review will examine the multitude of mechanisms by which steroid hormones induce these permanent changes in brain structure and function. Elucidating how steroids alter brain development sheds light on how individual variation in neuronal phenotype is established during a critical period. [source] Molecular and Cellular Events in Alcohol-Induced Muscle DiseaseALCOHOLISM, Issue 12 2007Joaquim Fernandez-Solà Alcohol consumption induces a dose-dependent noxious effect on skeletal muscle, leading to progressive functional and structural damage of myocytes, with concomitant reductions in lean body mass. Nearly half of high-dose chronic alcohol consumers develop alcoholic skeletal myopathy. The pathogenic mechanisms that lie between alcohol intake and loss of muscle tissue involve multiple pathways, making the elucidation of the disease somewhat difficult. This review discusses the recent advances in basic and clinical research on the molecular and cellular events involved in the development of alcohol-induced muscle disease. The main areas of recent research interest on this field are as follows: (i) molecular mechanisms in alcohol exposed muscle in the rat model; (ii) gene expression changes in alcohol exposed muscle; (iii) the role of trace elements and oxidative stress in alcoholic myopathy; and (iv) the role of apoptosis and preapoptotic pathways in alcoholic myopathy. These aforementioned areas are crucial in understanding the pathogenesis of this disease. For example, there is overwhelming evidence that both chronic alcohol ingestion and acute alcohol intoxication impair the rate of protein synthesis of myofibrillar proteins, in particular, under both postabsorptive and postprandial conditions. Perturbations in gene expression are contributory factors to the development of alcoholic myopathy, as ethanol-induced alterations are detected in over 400 genes and the protein profile (i.e., the proteome) of muscle is also affected. There is supportive evidence that oxidative damage is involved in the pathogenesis of alcoholic myopathy. Increased lipid peroxidation is related to muscle fibre atrophy, and reduced serum levels of some antioxidants may be related to loss of muscle mass and muscle strength. Finally, ethanol induces skeletal muscle apoptosis and increases both pro- and antiapoptotic regulatory mechanisms. [source] Genetic instabilities of (CCTG)·(CAGG) and (ATTCT)·(AGAAT) disease-associated repeats reveal multiple pathways for repeat deletionMOLECULAR CARCINOGENESIS, Issue 4 2009Sharon F. Edwards Abstract The DNA repeats (CTG)·(CAG), (CGG)·(CCG), (GAA)·(TTC), (ATTCT)·(AGAAT), and (CCTG)·(CAGG), undergo expansion in humans leading to neurodegenerative disease. A genetic assay for repeat instability has revealed that the activities of RecA and RecB during replication restart are involved in a high rate of deletion of (CTG)·(CAG) repeats in E. coli. This assay has been applied to (CCTG)·(CAGG) repeats associated with myotonic dystrophy type 2 (DM2) that expand to 11,000 copies and to spinocerebellar ataxia type 10 (SCA10) (ATTCT)·(AGAAT) repeats that expand to 4500 copies in affected individuals. DM2 (CCTG)·(CAGG) repeats show a moderate rate of instability, less than that observed for the myotonic dystrophy type 1 (CTG)·(CAG) repeats, while the SCA10 (ATTCT)·(AGAAT) repeats were remarkably stable in E. coli. In contrast to (CTG)·(CAG) repeats, deletions of the DM2 and SCA10 repeats were not dependent on RecA and RecB, suggesting that replication restart may not be a predominant mechanism by which these repeats undergo deletion. These results suggest that different molecular mechanisms, or pathways, are responsible for the instability of different disease-associated DNA repeats in E. coli. These pathways involve simple replication slippage and various sister strand exchange events leading to deletions or expansions, often associated with plasmid dimerization. The differences in the mechanisms of repeat deletion may result from the differential propensity of these repeats to form various DNA secondary structures and their differential proclivity for primer,template misalignment during replication. © 2009 Wiley-Liss, Inc. [source] Adaptation of the Lyme disease spirochaete to the mammalian host environment results in enhanced glycosaminoglycan and host cell bindingMOLECULAR MICROBIOLOGY, Issue 5 2003Nikhat Parveen Summary The Lyme disease spirochaete, Borrelia burgdorferi, is transmitted to mammals by Ixodes ticks and can infect multiple tissues. Host cell attachment may be critical for tissue colonization, and B. burgdorferi cultivated in vitro recognizes heparin- and dermatan sulphate-related glycosaminoglycans (GAGs) on the surface of mammalian cells. To determine whether growth of the spirochaete in the mammalian host alters GAG binding, we assessed the cell attachment activities of B. burgdorferi grown in vitro or in dialysis membrane chambers implanted intraperitoneally in rats. Host-adapted B. burgdorferi exhibited approximately threefold better binding to purified heparin and dermatan sulphate and to GAGs expressed on the surface of cultured endothelial cells. Three B. burgdorferi surface proteins, Bgp, DbpA and DbpB, have been demonstrated previously to bind to GAGs or to GAG-containing molecules, and we show here that recombinant derivatives of each of these proteins were able to bind to purified heparin and dermatan sulphate. Immunofluorescent staining of in vitro -cultivated or host-adapted spirochaetes revealed that DbpA and DbpB were present on the bacterial surface at higher levels after host adaptation. Recombinant Bgp, DbpA and DbpB each partially inhibited attachment of host-adapted B. burgdorferi to cultured mammalian cells, consistent with the hypothesis that these proteins may promote attachment of B. burgdorferi during growth in the mammalian host. Nevertheless, the partial nature of this inhibition suggests that multiple pathways promote mammalian cell attachment by B. burgdorferi in vivo. Given the observed increase in cell attachment activity upon growth in the mammalian host, analysis of host-adapted bacteria will facilitate identification of the cell binding pathways used in vivo. [source] Electrophysiologic Characteristics and Radiofrequency Catheter Ablation in Children with Wolff-Parkinson-White SyndromePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2006PI-CHANG LEE Background: The majority of cardiac arrhythmias in children are supraventricular tachycardia, which is mainly related to an accessory pathway (AP)-mediated reentry mechanism. The investigation for Wolff-Parkinson-White (WPW) syndrome in adults is numerous, but there is only limited information for children. This study was designed to evaluate the specific electrophysiologic characteristics and the outcome of radiofrequency (RF) catheter ablation in children with WPW syndrome. Methods: From December 1989 to August 2005, a total of 142 children and 1,219 adults with atrioventricular reentrant tachycardia (AVRT) who underwent ablation at our institution were included. We compared the clinical and electrophysiologic characteristics between children and adults with WPW syndrome. Results: The incidence of intermittent WPW syndrome was higher in children (7% vs 3%, P=0.025). There was a higher occurrence of rapid atrial pacing needed to induce tachycardia in children (67% vs 53%, P=0.02). However, atrial fibrillation (AF) occurred more commonly in adult patients (28% vs 16%, P = 0.003). The pediatric patients had a higher incidence of multiple pathways (5% vs 1%, P < 0.001). Both the onset and duration of symptoms were significantly shorter in the pediatric patients. The antegrade 1:1 AP conduction pacing cycle length (CL) and antegrade AP effective refractory period (ERP) in children were much shorter than those in adults with manifest WPW syndrome. Furthermore, the retrograde 1:1 AP conduction pacing CL and retrograde AP ERP in children were also shorter than those in adults. The antegrade 1:1 atrioventricular (AV) node conduction pacing CL, AV nodal ERP, and the CL of the tachycardia were all shorter in the pediatric patients. Conclusion: This study demonstrated the difference in the electrophysiologic characteristics of APs and the AV node between pediatric and adult patients. RF catheter ablation was a safe and effective method to manage children with WPW syndrome. [source] Age distributions, birth weights, nephrogenic rests, and heterogeneity in the pathogenesis of Wilms tumorPEDIATRIC BLOOD & CANCER, Issue 3 2006Norman E. Breslow PhD Abstract Background The National Wilms Tumor Study (NWTS) constitutes a unique resource for study of clinical, pathologic, and epidemiologic features of Wilms tumor (WT). Procedure Data from NWTS-3,4,5 were compiled for 7,455 patients with tumors of favorable (FH) or anaplastic (AH) histology. The associations of birth weight (BW) and age-at-onset with gender, intralobar (ILNR), and perilobar (PLNR) nephrogenic rests, tumor focality, congenital malformation syndromes, and tumor histology were analyzed using descriptive statistics and linear regression. Results Mean BWs for male and female patients without PLNR were 3.52 and 3.36 kg, respectively, and for those with PLNR were 0.12 kg and 0.15 kg heavier. Mean age was 45 months for males with no rests whose tumors were unifocal and of triphasic favorable histology. ILNR or multifocality decreased the mean age by 18 and 10 months, respectively, whereas female gender, blastemal/FH or AH increased it by 3, 10, and 16 months. Over 90% of multifocal tumors occurred in the presence of demonstrated ILNR or PLNR or both. The apparent bimodality of the age distributions and later mean ages-at-onset for females with both unifocal and multifocal tumors were explained in part by the relative deficit in females of ILNR versus PLNR-associated tumors. Conclusions These observations support the view that there are multiple pathways to Wilms tumorigenesis. They will facilitate selection of informative subgroups of patients for molecular analysis that may serve to identify the putative pathway for the majority of patients who cannot be classified provisionally on the basis of ILNR or PLNR. Pediatr Blood Cancer 2006;47:260,267. © 2006 Wiley-Liss, Inc. [source] Thin film solar modules: the low cost, high throughput and versatile alternative to Si wafersPROGRESS IN PHOTOVOLTAICS: RESEARCH & APPLICATIONS, Issue 5 2006S. Hegedus Abstract Thin film solar cells (TFSC) have passed adolescence and are ready to make a substantial contribution to the world's electricity generation. They can have advantages over c-Si solar modules in ease of large area, lower cost manufacturing and in several types of applications. Factors which limit TFSC module performance relative to champion cell performance are discussed along with the importance of increased throughput and yield. The consensus of several studies is that all TFSC can achieve costs below 1,$/W if manufactured at sufficiently large scale >100,MW using parallel lines of cloned equipment with high material utilization and spray-on encapsulants. There is significant new commercial interest in TFSC from small investors and large corporations, validating the thin film approach. Unique characteristics are discussed which give TFSC an advantage over c-Si in two specific markets: small rural solar home systems and building integrated photovoltaic installations. TFSC have outperformed c-Si in annual energy production (kWhrs/kW), have demonstrated outdoor durability comparable to c-Si and are being used in MW scale installations worldwide. The merits of the thin film approach cannot be judged on the basis of efficiency alone but must also account for module performance and potential for low cost. TFSC advocates should promote their unique virtues compared to c-Si: lower cost, higher kWhr/kW output, higher battery charging current, attractive visual appearance, flexible substrates, long-term stability comparable to c-Si, and multiple pathways for deposition with room for innovation and evolutionary improvement. There is a huge market for TFSC even at today's efficiency if costs can be reduced. A brief window of opportunity exists for TFSC over the next few years due the Si shortage. The demonstrated capabilities and advantages of TFSC must be proclaimed more persistently to funding decision-makers and customers without minimizing the remaining challenges. Copyright © 2006 John Wiley & Sons, Ltd. [source] The Complexity of Trauma Types in the Lives of Women in Families Referred for Family Violence: Multiple Mediators of Mental HealthAMERICAN JOURNAL OF ORTHOPSYCHIATRY, Issue 4 2008Victoria L. Banyard PhD Responding to calls for further research about the impact of multiple types of trauma across the life span, this study examines the interconnections among types of trauma in childhood and adulthood in a convenience clinical sample of 283 women obtaining social services for family violence. In particular, variables including family of-origin dysfunction and other childhood risk factors, relationship victimization in adulthood, and the presence of adult resources were examined as mediators of links between child maltreatment and adult mental health symptoms. Variables were assessed at different time points, 3 years apart. Path analysis revealed that the conceptual model of multiple pathways between childhood family violence exposure and adult outcomes fit the data well. In particular, the link between child maltreatment and adult trauma symptoms was mediated by more proximal adult sexual and intimate partner violence and its association with childhood risk markers (e.g., negative family environment) and decreased markers of resources. This link was not significant for a more general index of mental health symptoms in adulthood. [source] Change of the unbinding mechanism upon a mutation: A molecular dynamics study of an antibody,hapten complexPROTEIN SCIENCE, Issue 10 2005Raffaele Curcio Abstract We study forced unbinding of fluorescein from the wild type (WT) and a mutant [H(H58)A] of the single-chain variable-fragment (scFv) anti-fluorescein antibody FITC-E2 by molecular dynamics simulations using various pulling techniques. A large number of long simulations were needed to obtain statistically meaningful results as both the wild type and the H(H58)A mutant unbinding occurs through multiple pathways, often with metastable intermediates. For the wild type, the rate-limiting step in the unbinding process corresponds to the breaking of the non-native interactions characteristic of a specific intermediate. The H(H58)A mutation disfavors the occurrence of this intermediate. Two events where the hapten partially unbinds in the absence of pulling force are observed in extensive equilibrium simulations of the wild type, and their analysis indicates that forced unbinding and spontaneous unbinding proceed along similar pathways. The different unbinding mechanisms observed in the simulations suggest a possible reason for the difference in the experimental off-rate between the two antibodies. We predict mutations that are expected to modulate the occurrence of the unbinding intermediate. For two such new mutants [H(H58)A and S(H52)A], our predictions are validated in silico by additional simulations. The accompanying paper in this issue by Honegger et al. reports the X-ray structure of FITC-E2 with a derivative of fluorescein, which was used as the starting conformation for the work presented here. [source] Tic40 is important for reinsertion of proteins from the chloroplast stroma into the inner membraneTHE PLANT JOURNAL, Issue 5 2008Chi-Chou Chiu Summary Chloroplast inner-membrane proteins Tic40 and Tic110 are first imported from the cytosol into the chloroplast stroma, and subsequently reinserted from the stroma into the inner membrane. However, the mechanism of reinsertion remains unclear. Here we show that Tic40 itself is involved in this reinsertion process. When precursors of either Tic40 or a Tic110 C-terminal truncate, tpTic110-Tic110N, were imported into chloroplasts isolated from a tic40 -null mutant, soluble Tic40 and Tic110N intermediates accumulated in the stroma of tic40 -mutant chloroplasts, due to a slower rate of reinsertion. We further show that a larger quantity of soluble Tic21 intermediates also accumulated in the stroma of tic40 -mutant chloroplasts. In contrast, inner-membrane insertion of the triose-phosphate/phosphate translocator was not affected by the tic40 mutation. Our data suggest that multiple pathways exist for the insertion of chloroplast inner-membrane proteins. [source] Pond attributes influence competitive interactions between tadpoles and mosquito larvaeAUSTRAL ECOLOGY, Issue 4 2002Allie Mokany Abstract Tadpoles and mosquito larvae often coexist in natural freshwater bodies. We studied competitive interactions between: (i) tadpoles of the striped marsh frog (Limnodynastes peronii) and larvae of the mosquito Culex quinquefasciatus; and (ii) tadpoles of the common eastern froglet (Crinia signifera) and larvae of the mosquito Aedes australis. These two sets of taxa occur in natural water bodies in the Sydney region. Laboratory trials revealed competition between mosquito larvae and tadpoles in both systems. For example, mosquitoes displayed reduced rates of survival, growth and development, and smaller size at metamorphosis, when they were raised with tadpoles. The intensity of competitive suppression was influenced by attributes such as pond size (and hence, larval density), the location of food (on the water surface vs the substrate), and the extent of opportunities for direct physical interactions between the two competing organisms. These effects differed between the two study systems, suggesting that the mechanisms of suppression also differed. Limnodynastes peronii tadpoles suppressed C. quinquefasciatus even when the two types of organisms were separated by a physical partition, suggesting that chemical or microbiological cues may be responsible. Pond attributes also affected the impact of C. signifera tadpoles on Aedes larvae, but (unlike the Limnodynastes,Culex system) these effects disappeared when densities were lowered or when the tadpoles and mosquito larvae were physically separated. Thus, direct physical interactions may suppress mosquitoes in the Crinia,Aedes system. Our results suggest that tadpoles suppress the viability of larval mosquitoes by multiple pathways. [source] Pathological interactions with the timing of birth and uterine activationAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 6 2007Roger SMITH Abstract The physiological processes that regulate the onset of parturition and birth are slowly being elucidated, and the points at which pathology can intervene are becoming more apparent. The data support the view that multiple pathways lead to myometrial activation. The clinical corollary is that combinations of tocolytics that operate via different mechanisms may be more effective than single agents. It may also be necessary to divide preterm labour into groups based on underlying mechanisms and to tailor therapy accordingly. [source] | |||||||||||||||||||||||||||||||