bluuebunny/crossref_metadata_2025_split huggingface dataset:
Candida albicans Cyr1, Cap1 and G‐actin form a sensor/effector apparatus for activating cAMP synthesis in hyphal growth
Authors: Zou Hao , Fang Hao‐Ming , Zhu Yong , Wang Yue 
Published: November 2009

SummaryA key virulence trait of Candida albicans is its ability to undergo the yeast‐to‐hyphal growth transition in response to environmental signals. This transition critically requires a rapid activation of the adenylyl cyclase Cyr1 to generate a cAMP spike. However, the identity of the signal sensors and mechanisms of signal processing and integration remain largely unclear. Recent evidence suggests that some sensors are embedded in Cyr1 itself. To test this hypothesis, we asked whether purified Cyr1 can respond to hyphal induction. Here, we report that Cyr1 co‐purifies with Cap1 and G‐actin as a tripartite complex which can increase cAMP synthesis in response to hyphal inducing signals in an actin‐dependent manner. Cap1 binds Cyr1 and G‐actin through its N‐ and C‐terminus respectively. Deleting the G‐actin binding sites or treating the complex with the actin toxin latrunculin A or cytochalasin A inhibits the activation of cAMP synthesis. Strains expressing Cap1 mutants lacking the G‐actin binding site are impaired in both cAMP synthesis and hyphal morphogenesis. Thus, our findings reveal an essentially intact sensor/effector apparatus composed of Cyr1, Cap1 and G‐actin. Furthermore, G‐actin's regulatory role in this apparatus may prove to be the missing link whereby cellular actin status knowingly influences cAMP‐mediated cellular processes.
Genetics of the glutamate‐mediated methylamine utilization pathway in the facultative methylotrophic beta‐proteobacterium Methyloversatilis universalis FAM5
Authors: Latypova Ekaterina , Yang Song , Wang Yi‐Shun , Wang Tiansong , Chavkin Theodore A. , Hackett Murray , Schäfer Hendrik , Kalyuzhnaya Marina G. 
Published: November 2009

SummaryThe ability of some microbial species to oxidize monomethylamine via glutamate‐mediated pathways was proposed in the 1960s; however, genetic determinants of the pathways have never been described. In the present study we describe a gene cluster essential for operation of the N‐methylglutamate pathway in the methylotrophic beta‐proteobacterium Methyloversatilis universalis FAM5. Four major polypeptides from protein fractions displaying high activities of N‐methylglutamate synthetase, N‐methylglutamate dehydrogenase and γ‐glutamylmethylamide synthetase were selected for mass spectrometry‐based identification. The activities of enzymes were associated with the presence of peptides identified as ferredoxin‐dependent glutamate synthase (GltB2), large subunit of putative heterotetrameric sarcosine oxidase (SoxA) and glutamine synthetase type III (GSIII) respectively. A gene cluster (8.3 kb) harbouring gltB2, soxA and gsIII‐like genes was amplified from M. universalis FAM5, sequenced and assembled. Two partial and six complete open reading frames arranged in the order soxBDAG‐gsIII‐gltB132 were identified and subjected to mutational analysis, functional and metabolic profiling. We demonstrated that gltB‐like and sox‐like genes play a key role in methylamine utilization and encode N‐methylglutamate synthetase and N‐methylglutamate dehydrogenase respectively. Metabolic, enzymatic and mutational analyses showed that the gsIII‐like gene encodes γ‐glutamylmethylamide synthetase; however, this enzyme is not essential for oxidation of methylamine.
Immunohistological intensity measurements as a tool to assess sarcolemma‐associated protein expression
Authors: Arechavala‐Gomeza V. , Kinali M. , Feng L. , Brown S. C. , Sewry C. , Morgan J. E. , Muntoni F. 
Published: November 2009

V. Arechavala‐Gomeza, M. Kinali, L. Feng, S. C. Brown, C. Sewry, J. E. Morgan and F. Muntoni (2010) Neuropathology and Applied Neurobiology36, 265–274 Immunohistological intensity measurements as a tool to assess sarcolemma‐associated protein expression Aims: The quantification of protein levels in muscle biopsies is of particular relevance in the diagnostic process of neuromuscular diseases, but is difficult to assess in cases of partial protein deficiency, particularly when information on protein localization is required. The combination of immunohistochemistry and Western blotting is often used in these cases, but is not always possible if the sample is scarce. We therefore sought to develop a method to quantify relative levels of sarcolemma‐associated proteins using digitally captured images of immunolabelled sections of skeletal muscle. Methods: To validate our relative quantification method, we labelled dystrophin and other sarcolemmal proteins in transverse sections of muscle biopsies taken from Duchenne muscular dystrophy and Becker muscular dystrophy patients, a manifesting carrier of Duchenne muscular dystrophy and normal controls. Results: Using this method to quantify relative sarcolemmal protein abundance, we were able to accurately distinguish between the different patients on the basis of the relative amount of dystrophin present. Conclusions: This comparative method adds value to techniques that are already part of the diagnostic process and can be used with minimal variation of the standardized protocols, without using extra amounts of valuable biopsy samples. Comparative quantification of sarcolemmal proteins on immunostained muscle sections will be of use to establish both the abundance and localization of the protein. Moreover, it can be applied to assess the efficacy of experimental therapies where only partial restoration or upregulation of the protein may occur.
Control of leaf growth by abscisic acid: hydraulic or non‐hydraulic processes?
Authors: TARDIEU FRANÇOIS , PARENT BORIS , SIMONNEAU THIERRY 
Published: November 2009

ABSTRACTAbscisic acid (ABA) affects plant metabolism and water transfers via multiple mechanisms at cell, organ and whole plant levels. These mechanisms translate into contradictory effects on leaf growth, so the literature reports positive, null or negative effects of ABA on leaf growth upon water deficit. We review evidences based on genetic manipulations of ABA biosynthesis, feeding the plant with artificial ABA or partial root drying and provide elements to avoid confusions of effects. We propose that ABA has mainly three effects on growth. (i) Via its controlling effect on stomatal aperture and transpiration rate, an increased concentration of ABA tends to buffer the day‐night alternations of leaf growth rate and the negative effect of evaporative demand. (ii) ABA tends to improve leaf growth via an increase in the conductance to water transfer in the plant as a result of increased tissue hydraulic conductivity. (iii) ABA has also a modest non‐hydraulic effect which is negative in plants subjected to water deficit, either manipulated for ABA synthesis or fed with artificial ABA, but can be positive in well watered plants deficient of ABA. The overall effect of increasing ABA biosynthesis depends on the relative weight of each of these effects under different environmental scenarios.
Making the most of drought and salinity transcriptomics
Authors: DEYHOLOS MICHAEL K. 
Published: November 2009

ABSTRACTMore than 100 different studies of plant transcriptomic responses to salinity or drought‐related stress have now been published. Most of these use microarrays or related high‐throughput profiling technologies. This compels us to ask three questions in review: (1) what has transcriptomics contributed to our understanding of stress physiology; (2) what limits the ability of transcriptomics to contribute to increases in stress tolerance; and (3) given these limits, what are the most appropriate uses of transcriptomics? We conclude that although microarrays are now a mature technology that accurately describes the transcriptome, the consistently low correlation between transcript abundance and other measures of gene expression imposes an inherent limitation that cannot be ignored. Further limitations on the relevance of transcriptomics arise in some cases from experimental practices related to the treatment regimen and the selection of tissue or germplasm. Nevertheless, there is good evidence to support the continued use of transcriptomics, especially emerging techniques such as RNA‐Seq, as a screening tool for candidate gene discovery. Microarrays can also be valuable in analysing the transcriptome per se (e.g. when describing the phenotype of a transcription factor mutant or discovering non‐coding RNA species), and when integrated with other types of data including metabolomic analyses.
TLR‐related pathway analysis: novel gene–gene interactions in the development of asthma and atopy
Authors: Reijmerink N. E. , Bottema R. W. B. , Kerkhof M. , Gerritsen J. , Stelma F. F. , Thijs C. , Van Schayck C. P. , Smit H. A. , Brunekreef B. , Koppelman G. H. , Postma D. S. 
Published: November 2009

To cite this article: Reijmerink NE, Bottema RWB, Kerkhof M, Gerritsen J, Stelma FF, Thijs C, van Schayck CP, Smit HA, Brunekreef B, Koppelman GH, Postma DS. TLR‐related pathway analysis: novel gene–gene interactions in the development of asthma and atopy. Allergy 2010; 65: 199–207.AbstractBackground:  The toll‐like receptor (TLR)‐related pathway is important in host defence and may be crucial in the development of asthma and atopy. Numerous studies have shown associations of TLR‐related pathway genes with asthma and atopy phenotypes. So far it has not been investigated whether gene–gene interactions in this pathway contribute to atopy and asthma development.Methods:  One hundred and sixty‐nine haplotype tagging single nucleotide polymorphisms (SNPs) of 29 genes (i.e. membrane and intracellular receptors, TLR4 or lipopolysaccharide‐binding/facilitating proteins, adaptors, interleukin‐1 receptor associated kinases, kinases, chaperone molecules, transcription factors and inhibitors) were analysed for single‐ and multilocus associations with atopy [total and specific immunglobulin E (IgE) at 1–2 and 6–8 years] and asthma (6–8 years). A total of 3062 Dutch children from the birth cohorts PIAMA, PREVASC and KOALA (Allergenic study) were investigated. Chi‐squared test, logistic regression and the data mining approach multifactor dimensionality reduction method (MDR) were used in analysis.Results:  Several genes in the TLR‐related pathway were associated with atopy and/or asthma [e.g. IL1RL1, BPI, NOD1, NOD2 and MAP3K7IP1]. Multiple, single associations were found with the phenotypes under study. MDR analysis showed novel, significant gene–gene interactions in association with atopy and asthma phenotypes (e.g. IL1RL1 and TLR4 with sIgE to indoor allergens and IRAK1, NOD1 and MAP3K7IP1 with asthma). Interestingly, gene–gene interactions were identified with SNPs that did not have an effect on their own.Conclusion:  Our unbiased approach provided suggestive evidence for interaction between several TLR‐related pathway genes important in atopy and/or asthma development and pointed to novel genes.
Opposing roles of IL‐17A and IL‐25 in the regulation of TSLP production in human nasal epithelial cells
Authors: Xu G. , Zhang L. , Wang D. Y. , Xu R. , Liu Z. , Han D. M. , Wang X. D. , Zuo K. J. , Li H. B. 
Published: November 2009

To cite this article: Xu G, Zhang L, Wang DY, Xu R, Liu Z, Han DM, Wang XD, Zuo KJ, Li HB. Opposing roles of IL‐17A and IL‐25 in the regulation of TSLP production in human nasal epithelial cells. Allergy 2010; 65: 581–589.AbstractBackground:  The importance of IL‐17A, IL‐17F, and IL‐25 in allergic rhinitis (AR), as well as their possible role in regulation on thymic stromal lymphopoietin (TSLP) production in nasal epithelial cells, is not well understood.Objective:  To determine the possible regulation of IL‐17A, IL‐17F, and IL‐25 on TSLP production in the initiation of allergic responses.Methods:  The levels of IL‐17A, IL‐17F, IL‐25, and TSLP in nasal lavages of patients with AR were measured using an enzyme‐linked immunosorbent assay (ELISA) and compared with that in normal controls. Then, primary human nasal epithelial cells (HNECs) were stimulated with dsRNA (0–75 μg/ml), as well as IL‐17A (100 ng/ml), IL‐17F (100 ng/ml), and IL‐25(100 ng/ml). The mRNA expression of IL‐17A, IL‐17F, IL‐25, TSLP, as well as the chemokines CCL20, IL‐8, and eotaxin was analyzed using quantitative real‐time PCR, and their protein levels in the supernatants of cultured HNECs were determined by ELISA.Results:  Both TSLP and IL‐17 cytokines are significantly elevated in patients with AR. dsRNA was found to increase the production of IL‐17F, IL‐25, TSLP, CCL20, and IL‐8 in HNECs. Furthermore, IL‐25 significantly enhanced dsRNA‐induced TSLP production in primary HNECs and was dominant to the inhibitory effect of IL‐17A on TSLP regulation.Conclusions:  Our study provides the first evidence that both IL‐17F and IL‐25 can be induced by dsRNA in HNECs. Despite of the opposing effects of IL‐17A and IL‐25 on TSLP regulation in HNECs, IL‐25 was dominant to IL‐17A, providing a plausible explanation for the simultaneous upregulation of IL‐17 cytokines and TSLP in patients with AR.
Gene–gene and gene–environment interactions on IgE production in prenatal stage
Authors: Yang K. D. , Chang J.‐C. , Chuang H. , Liang H.‐M. , Kuo H.‐C. , Lee Y.‐S. , Hsu T.‐Y. , Ou C.‐Y. 
Published: November 2009

To cite this article: Yang KD, Chang J‐C, Chuang H, Liang H‐M, Kuo H‐C, Lee Y‐S, Hsu T‐Y, Ou C‐Y. Gene–gene and gene–environment interactions on IgE production in prenatal stage. Allergy 2010; 65: 731–739.AbstractBackground:  Prevalence of allergic diseases in children has increased worldwide over the past decades. Allergy sensitization may occur in fetal life. This study investigated whether gene–gene and gene–environment interactions affected cord blood IgE (CBIgE) levels.Methods:  A total of 575 cord blood DNA samples were subjected to a multiplex microarray for 384 single nucleotide polymorphisms (SNPs) in 159 allergy candidate genes. Genetic association was initially assessed by univariate and multivariate analyses. Multifactor dimensionality reduction (MDR) was used to identify gene–gene and gene–environment interactions. Environmental factors for analysis included maternal atopy, paternal atopy, parental smoking, gender, and prematurity.Results:  Twenty‐one SNPs in 14 genes were associated with CBIgE elevation (≥0.5 KU/l) in univariate analysis. Multivariate analysis identified eleven genes (IL13, IL17A, IL2RA, CCL17, CXCL1, PDGFRA, FGF1, HAVCR1, GNAQ, C11orf72, and ADAM33) which were significantly associated with CBIgE elevation. MDR analyses of gene–gene interactions identified IL13 interacted with IL17A and/or redox genes on CBIgE elevation with the prediction accuracy of 62.52%. Analyses of gene–environment interactions identified that maternal atopy combined with IL13, rs1800925 and CCL22, rs170359 SNPs had the highest prediction accuracy of 67.15%. All the high and low risk classifications on gene–gene and gene–environment interactions by MDR analyses could be validated by Chi‐square test.Conclusions:  Gene–gene (e.g. immune and redox genes) and gene–environment (e.g. maternal atopy and FGF1or redox genes) interactions on IgE production begin in prenatal stage, suggesting that prevention of IgE‐mediated diseases may be made possible by control of maternal atopy and redox responses in prenatal stage.
Proliferative drive and liver carcinogenesis: Too much of a good thing?
Authors: Teoh Narci C 
Published: November 2009

AbstractThere have been innumerable studies published in the attempt to identify gene expression signatures in hepatocellular carcinoma (HCC). When all the regulators and targets of the differentially expressed genes are analyzed from larger studies, the most striking theme is upregulation of mitosis‐promoting and cell proliferation genes in HCC compared with ‘liver‐specific gene clusters’ in non‐tumorous tissue. A major limitation of expression profiling is that it only provides a ‘snapshot’ of what is an evolving process and thus cannot distinguish the differences in gene expression that are primary effectors of dysregulated growth from those that represent downstream consequences. The development of HCC in a chronically diseased liver, often referred to as hepatocarcinogenesis, is a multistep process characterized by the progressive accumulation and interplay of genetic alterations causing aberrant growth, malignant transformation of liver parenchymal cells, followed by vascular invasion and metastasis. This review will discuss HCC precursor lesions, draw on the ‘proliferation cluster’ genes highlighted from HCC expression profiling studies, relate them to a selection of regulatory networks important in liver regeneration, cell cycle control and their potential significance in the pathogenesis of HCC or primary liver cancer.
Epidemiology of colorectal cancer in Asia
Authors: Yee Yuk Kei , Tan Victoria PY , Chan Pierre , Hung Ivan FN , Pang Roberta , Wong Benjamin CY 
Published: November 2009

AbstractThe prevalence of colorectal cancer is increasing in Asia. However, the age‐standardized rate has reached a plateau in some countries. Some studies have shown a male predominance difference and increasing risk in the elderly, but not in the younger population. ‘Right shifting’ of colorectal cancer, not accountable by difference in age or the indications for endoscopic examination, has also been noted. Westernized diet is associated with colorectal cancer, but controversy remains on how it causes colorectal cancer. Alcohol consumption, obesity, diabetes mellitus, consumption of red and processed meat and cigarette smoking are linked to bowel cancer epidemiologically. Only high dietary calcium has a consistent negative (or ‘protective’) effect. The efficacy of fish oil, vitamin D, soy, phytoestrogens, folate, methionine, riboflavin and vitamin B6 has not been established. Aspirin and non‐steroidal anti‐inflammatory drugs use decrease risk of colorectal cancer after 5–10 years of use. There is no evidence for a detrimental effect of proton pump inhibitors or benefit of statins in colorectal cancer. In conclusion, there is a rising trend and prevalence of colorectal cancer in Asia. Dietary modification or supplementation may not be effective in preventing colorectal cancer. Surveillance of colorectal cancer in high‐risk groups, according to current recommendation, is probably most effective.
Maintenance of the relative proportion of oligodendrocytes to axons even in the absence of BAX and BAK
Authors: Kawai Kumi , Itoh Takayuki , Itoh Aki , Horiuchi Makoto , Wakayama Kouji , Bannerman Peter , Garbern James Y. , Pleasure David , Lindsten Tullia 
Published: November 2009

AbstractHighly purified oligodendroglial lineage cells from mice lacking functional bax and bak genes were resistant to apoptosis after in‐vitro differentiation, indicating an essential role of the intrinsic apoptotic pathway in apoptosis of oligodendrocytes in the absence of neurons (axons) and other glial cells. These mice therefore provide a valuable tool with which to evaluate the significance of the intrinsic apoptotic pathway in regulating the population sizes of oligodendrocytes and oligodendroglial progenitor cells. Quantitative analysis of the optic nerves and the dorsal columns of the spinal cord revealed that the absolute numbers of mature oligodendrocytes immunolabeled for aspartoacylase and adult glial progenitor cells expressing NG2 chondroitin sulfate proteoglycan were increased in both white matter tracts of adult bax/bak‐deficient mice and, to a lesser extent, bax‐deficient mice, except that there was no increase in NG2‐positive progenitor cells in the dorsal columns of these strains of mutant mice. These increases in mature oligodendrocytes and progenitor cells in bax/bak‐deficient mice were unexpectedly proportional to increases in numbers of axons in these white matter tracts, thus retaining the oligodendroglial lineage to axon ratios of at most 1.3‐fold of the physiological numbers. This is in contrast to the prominent expansion in numbers of neural precursor cells in the subventricular zones of these adult mutant mice. Our study indicates that homeostatic control of cell number is different for progenitors of the oligodendroglial and neuronal lineages. Furthermore, regulatory mechanism(s) operating in addition to apoptotic elimination through the intrinsic pathway, appear to prevent the overproduction of highly mitotic oligodendroglial progenitor cells.
Short‐term synaptic plasticity at the main and vomeronasal olfactory receptor to mitral cell synapse in frog
Authors: Delaney K. R. , Qnais E. Y. , Hardy A. B. 
Published: November 2009

AbstractSynaptic responses resulting from stimulation of the main olfactory and vomeronasal (VN) nerves were measured in main and accessory olfactory bulb (AOB) of frog, Rana pipiens, to test the hypothesis that properties of these synapses would reflect the distinct differences in the time course of odour delivery to each of these olfactory structures. Paired‐pulse depression dominated responses to repetitive stimulation of the main olfactory nerve for interstimulus intervals (ISI) up to several seconds. Inhibition of voltage‐gated Ca2+ channels by GABAb receptors contributes significantly to this inhibition of transmitter release, particularly for ISI > 0.5 s. In contrast, the monosynaptic connection between VN sensory neurons and mitral cells in the AOB showed enhancement with pairs or short trains of stimuli for ISI of 0.5 to > 10 s. A small inhibitory effect of GABAb receptors on presynaptic Ca2+ influx and release was only evident when a large proportion of the VN axons were stimulated simultaneously but even with inhibition present an overall enhancement of release was observed. Increasing the number of conditioning stimuli from one to five increased residual [Ca2+] and enhancement but a direct correlation between residual [Ca2+] and either the magnitude or the time course of enhancement was not observed. Enhanced transmitter release from VN afferent terminals results in effective integration of sustained low‐frequency activity, which may play a role in the detection of low‐intensity odourant stimuli by the VN system.
Role of polysialylated neural cell adhesion molecule in rapid eye movement sleep regulation in rats
Authors: Black Michelle A. , Deurveilher Samüel , Seki Tatsunori , Marsh Daniel R. , Rutishauser Urs , Rafuse Victor F. , Semba Kazue 
Published: November 2009

AbstractRecent evidence suggests that synaptic plasticity occurs during homeostatic processes, including sleep–wakefulness regulation, although the underlying mechanisms are not well understood. Polysialylated neural cell adhesion molecule (PSA NCAM) is a transmembrane protein that has been implicated in various forms of plasticity. To investigate whether PSA NCAM is involved in the neuronal plasticity associated with spontaneous sleep–wakefulness regulation and sleep homeostasis, four studies were conducted using rats. First, we showed that PSA NCAM immunoreactivity is present in close proximity to key neurons in several nuclei of the sleep–wakefulness system, including the tuberomammillary hypothalamic nucleus, dorsal raphe nucleus, and locus coeruleus. Second, using western blot analysis and densitometric image analysis of immunoreactivity, we found that 6 h of sleep deprivation changed neither the levels nor the general location of PSA NCAM in the sleep–wakefulness system. Finally, we injected endoneuraminidase (Endo N) intracerebroventricularly to examine the effects of polysialic acid removal on sleep–wakefulness states and electroencephalogram (EEG) slow waves at both baseline and during recovery from 6 h of sleep deprivation. Endo N‐treated rats showed a small but significant decrease in baseline rapid eye movement (REM) sleep selectively in the late light phase, and a facilitated REM sleep rebound after sleep deprivation, as compared with saline‐injected controls. Non‐REM sleep and wakefulness were unaffected by Endo N. These results suggest that PSA NCAM is not particularly involved in the regulation of wakefulness or non‐REM sleep, but plays a role in the diurnal pattern of REM sleep as well as in some aspects of REM sleep homeostasis.