bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of Vibration-based Damage Identification Methods Using Displacement and Distributed Strain Measurements
Authors: Philips Adewuyi A. , Wu Zhishen , Kammrujaman Serker N.H.M.
Published: August 2009

Accurate measurement and monitoring of vibration characteristics is critical for proper detection of the location and severity of damage. However, experimentally measured modal properties are inevitably corrupted by measurement noise and errors, which could render most vibration-based structural damage identification algorithms unreliable for civil structural health monitoring (SHM). This article, through computer simulation and experimental investigation of a simply supported beam, comparatively evaluates the performance of these techniques for practical civil SHM by using displacement modes from accelerometers and long-gage distributed strain measurements. Most of all the techniques proved unreliable for damage identification using noisy measurements from accelerometers, while successful with distributed strain measurements. The findings reveal that long-gage distributed strain measurements are much more efficient choice over the traditional measurement techniques for reliable civil SHM. It may therefore be concluded that the performance of some algorithms might be improved for application to civil infrastructure by using distributed strain fiber optic sensing measurement techniques.
The Neurobiological Toll of Child Abuse and Neglect
Authors: Neigh Gretchen N. , Gillespie Charles F. , Nemeroff Charles B.
Published: August 2009

Exposure to interpersonal violence or abuse affects the physical and emotional well-being of affected individuals. In particular, exposure to trauma during development increases the risk of psychiatric and other medical disorders beyond the risks associated with adult violence exposure. Alterations in the hypothalamic-pituitary-adrenal (HPA) axis, a major mediating pathway of the stress response, contribute to the long-standing effects of early life trauma. Although early life trauma elevates the risk of psychiatric and medical disease, not all exposed individuals demonstrate altered HPA axis physiology, suggesting that genetic variation influences the consequences of trauma exposure. In addition, the effects of abuse may extend beyond the immediate victim into subsequent generations as a consequence of epigenetic effects transmitted directly to offspring and/or behavioral changes in affected individuals. Recognition of the biological consequences and transgenerational impact of violence and abuse has critical importance for both disease research and public health policy.
Noninflammatory mechanisms of airway hyper-responsiveness in bronchial asthma: an overview
Authors: Baroffio Michele , Barisione Giovanni , Crimi Emanuele , Brusasco Vito
Published: August 2009

Airway hyper-responsiveness (AHR) is a cardinal feature of asthma. Its absence has been considered useful in excluding asthma, whereas it may be present in other diseases such as atopic rhinitis and chronic obstructive pulmonary disease. AHR is often considered an epiphenomenon of airway inflammation. Actually, the response of airways to constrictor stimuli is modulated by a complex array of factors, some facilitating and others opposing airway narrowing. Thus, it has been suggested that AHR, and perhaps asthma, might be present even without or before the development of airway inflammation. We begin this review by highlighting some terminological and methodological issues concerning the measurement of AHR. Then we describe the neurohumoral mechanisms controlling airway tone. Finally, the pivotal role of airway smooth muscle and internal and external modulation of airway caliber in vivo are discussed in detail.
Diffusion in diamond. II. High-pressure-temperature experiments
Authors: Harte B. , Taniguchi T. , Chakraborty S.
Published: August 2009

High-pressure-temperature (P-T) experiments were conducted in an attempt to determine the diffusion rates of C atoms in diamond, and the possibility of changes in the isotope compositions of diamond at high P-T in the Earth’s mantle. The starting material consisted of a polished plate of natural diamond (very largely 12C), which had been coated with 13C diamond by chemical-vapourdeposition to form a sharp interface between 12C and 13C diamond. Three experiments were performed at 1800, 2000 and 2300ºC, all at 7.7 GPa, for0.5 –20 h. Isotopic profiles obtained by ion microprobe before and after each experiment showed no evidence of relaxation of the sharp interface between 12C and 13C, and so diffusion must have been on a scale less than the ~32 nm depth resolution for this technique. Using 32 nm as the maximum length scale of diffusion across the interface, the maximum ln D (diffusion coefficient) values for the experiments were calculated to be in the range –38 to –42. Unlike previous experimental data, these results show that changes in the isotopic compositions of diamond on long time scales in the Earth’s upper mantle are unlikely. Furthermore, the results support empirical evidence from mapping of C isotope distributions in natural diamonds that C isotope compositions reflect diamond growth compositions.
The geochemistry of Middle Jurassic dykes associated with the Straumsvola–Tvora alkaline plutons, Dronning Maud Land, Antarctica and their association with the Karoo large igneous province
Authors: Riley T. R. , Curtis M. L. , Leat P. T. , Millar I. L.
Published: August 2009

Jurassic dykes of western Dronning Maud Land (Antarctica) form a minor component of the Karoo large igneous province. An extensive local dyke swarm intrudes Neoproterozoic gneisses and Jurassic syenite plutons on the margins of the Jutulstraumen palaeo rift in the Svedrupfjella region. The dykes were intruded in three distinct episodes (~204, ~176 and ~170 Ma). The 204 Ma dykes are overwhelminglylow-Ti, olivine tholeiites including some primitive (picritic) compositions (MgO >12 wt.%; Fe2O3 >12 wt.%; Cr >1000 ppm; Ni >600 ppm). This 204 Ma event precedes the main Karoo volcanic event by~25 Ma, so anycorrelations to the wider province are difficult to make. However, it mayrecord the earliest phase of rift activity along the Jutulstraumen. The 176 Ma dyke event is more intimately associated with the two syenite plutons. The dykes are alkaline (basanite/ tephrite) and were small-degree melts from an enriched, locallyderived source and underwent at least some degree of interaction with a syenitic contaminant. This ~176 Ma dyke event is widespread elsewhere in the Karoo (southern Africa and Dronning Maud Land). Later-stage (170 Ma) felsic (phonolite–comendite) dykes intrude the 176 Ma basanite–tephrite suite and represent the last phase of magmatic activityin the region.
The crystal structure of tedhadleyite, Hg2+Hg101+O4l2(Cl,Br)2, from the Clear Creek Claim, San Benito County, California
Authors: Cooper M. A. , Hawthorne F. C.
Published: August 2009

The crystal structure of tedhadleyite, ideally Hg2+Hg101+O4l2(Cl,Br)2,triclinic, AĪ, a 7.0147(5), b 11.8508(7), c 12.5985(8) Å, α 115.583(5), β 82.575(2), γ 100.619(2)º, V 927.0(2) Å3, Z = 2,was solved by direct methods and refined to an R1 index of 4.5% for 2677 unique reflections. There are six symmetrically distinct Hg sites in tedhadleyite: Hg(1) is occupied by Hg2+ and Hg(2–6) are occupied by Hg+ that forms three [Hg–Hg]2+ dimers with Hg–Hg separations between 2.527 and 2.556 Å. These [Hg–Hg]2+ dimers have strong covalent bonds to O atoms,forming pseudo-linear O–Hg–Hg–O arrangements,and weak bonds to halogen and O atoms at high angles to the dimer axis. The [O–Hg–Hg-O] groups share anions to form four-membered square rings of composition [Hg8O4] that link along [100] via [O–Hg–Hg-O] groups and along [001] via [O–Hg–O] groups, forming rectangular rings of composition [Hg14O8]. The rings form a corrugated layer that interweaves with a symmetrically related layer whereby the [O–Hg(6)–Hg(6)–O] linking groups of one layer pass through the centres of the square [Hg8O4] rings of the other layer to form [Hg11O4] complex slabs parallel to (010) that link through Hg-I and Hg-Br,Cl bonds.
The crystal structure of Ba2F2(S6+O3S2–), a natural thiosulphate weathering product of old smelting slags at the Surrender Mill, Yorkshire, UK
Authors: Kampf A. R.
Published: August 2009

The crystal structure of Ba2F2(S6+O3S2–), a natural thiosulphate weathering product of old smelting slags at the Surrender Mill, Yorkshire, England, UK, has been solved to R1 = 0.88% for 399 unique [Fo > 4α F] reflections and 0.91% for all 407 reflections. The compound is monoclinic, C2/m, a 15.3172(5), b 4.5898(1), c 4.6320(2) Å, β 101.449(1)º, V 319.17(2) Å3. The structure of Ba2F2(S6+O3S2–) consists of BaF2Ba layer fragments of the fluorite-type structure of frankdicksonite (BaF2) parallel to (100) alternating with layers of thiosulphate groups. The layer sequence in one unit cell is (S6+O3S2–)-BaF2Ba-(S6+O3S2–)-BaF2Ba. The structure resembles that of grandreefite, Pb2F2SO4.
HIV-1 Tat and heparan sulfate proteoglycan interaction: a novel mechanism of lymphocyte adhesion and migration across the endothelium
Authors: Urbinati Chiara , Nicoli Stefania , Giacca Mauro , David Guido , Fiorentini Simona , Caruso Arnaldo , Alfano Massimo , Cassetta Luca , Presta Marco , Rusnati Marco
Published: August 2009

The HIV-1 transactivating factor Tat accumulates on the surface of endothelium by interacting with heparan sulfate proteoglycans (HSPGs). Tat also interacts with B-lymphoid Namalwa cells but only when these overexpress HSPGs after syndecan-1 cDNA transfection (SYN-NCs). Accordingly, SYN-NCs, but not mock-transfected cells, adhere to endothelial cells (ECs) when Tat is bound to the surface of either one of the 2 cell types or when SYN-NCs are transfected with a Tat cDNA. Moreover, endogenously produced Tat bound to cell-surface HSPGs mediates cell adhesion of HIV+ ACH-2 lymphocytes to the endothelium. This heterotypic lymphocyte-EC interaction is prevented by HSPG antagonist or heparinase treatment, but not by integrin antagonists and requires the homodimerization of Tat protein. Tat tethered to the surface of SYN-NCs or of peripheral blood monocytes from healthy donors promotes their transendothelial migration in vitro in response to CXCL12 or CCL5, respectively, and SYN-NC extravasation in vivo in a zebrafish embryo model of inflammation. In conclusion, Tat homodimers bind simultaneously to HSPGs expressed on lymphoid and EC surfaces, leading to HSPG/Tat-Tat/HSPG quaternary complexes that physically link HSPG-bearing lymphoid cells to the endothelium, promoting their extravasation. These data provide new insights about how lymphoid cells extravasate during HIV infection.
Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production
Authors: Choi Yeon-Sook , Choi Hyun-Jung , Min Jeong-Ki , Pyun Bo-Jeong , Maeng Yong-Sun , Park Hongryeol , Kim Jihye , Kim Young-Myeong , Kwon Young-Guen
Published: August 2009

Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is emerging as a new regulator of immune responses and inflammatory vascular diseases. Although IL-33 and its cognate receptor ST2 appear to be expressed in vascular cells, the precise role of IL-33 in the vasculature has not been determined. In this study, we report a novel role of IL-33 as a potent endothelial activator, promoting both angiogenesis and vascular permeability. IL-33 increased proliferation, migration, and morphologic differentiation of human endothelial cells, consistently with increased angiogenesis in vivo. IL-33 also increased endothelial permeability with reduced vascular endothelial–cadherin-facilitated cell–cell junctions in vitro and induced vascular leakage in mouse skin. These effects of IL-33 were blocked by knockdown of ST2. Ligation of IL-33 with ST2 rapidly increased endothelial nitric oxide (NO) production through TRAF6-mediated activation of phosphoinoside-3-kinase, Akt, and endothelial NO synthase. Moreover, pharmacologic or genetic blockage of endothelial NO generation resulted in the inhibition of angiogenesis and vascular hyperpermeability induced by IL-33. These data demonstrate that IL-33 promotes angiogenesis and vascular leakage by stimulating endothelial NO production via the ST2/TRAF6-Akt-eNOS signaling pathway. These findings open new perspectives for the role of IL-33 in the pathogenesis of angiogenesis-dependent and inflammatory vascular diseases.
R/BHC: fast Bayesian hierarchical clustering for microarray data
Authors: Savage Richard S , Heller Katherine , Xu Yang , Ghahramani Zoubin , Truman William M , Grant Murray , Denby Katherine J , Wild David L
Published: August 2009

Background

Although the use of clustering methods has rapidly become one of the standard computational approaches in the literature of microarray gene expression data analysis, little attention has been paid to uncertainty in the results obtained.

Results

We present an R/Bioconductor port of a fast novel algorithm for Bayesian agglomerative hierarchical clustering and demonstrate its use in clustering gene expression microarray data. The method performs bottom-up hierarchical clustering, using a Dirichlet Process (infinite mixture) to model uncertainty in the data and Bayesian model selection to decide at each step which clusters to merge.

Conclusion

Biologically plausible results are presented from a well studied data set: expression profiles of A. thaliana subjected to a variety of biotic and abiotic stresses. Our method avoids several limitations of traditional methods, for example how many clusters there should be and how to choose a principled distance metric.
Correlations between RNA and protein expression profiles in 23 human cell lines
Authors: Gry Marcus , Rimini Rebecca , Strömberg Sara , Asplund Anna , Pontén Fredrik , Uhlén Mathias , Nilsson Peter
Published: August 2009

Background

The Central Dogma of biology holds, in famously simplified terms, that DNA makes RNA makes proteins, but there is considerable uncertainty regarding the general, genome-wide correlation between levels of RNA and corresponding proteins. Therefore, to assess degrees of this correlation we compared the RNA profiles (determined using both cDNA- and oligo-based microarrays) and protein profiles (determined immunohistochemically in tissue microarrays) of 1066 gene products in 23 human cell lines.

Results

A high mean correlation coefficient (0.52) was obtained from the pairwise comparison of RNA levels determined by the two platforms. Significant correlations, with correlation coefficients exceeding 0.445, between protein and RNA levels were also obtained for a third of the specific gene products. However, the correlation coefficients between levels of RNA and protein products of specific genes varied widely, and the mean correlations between the protein and corresponding RNA levels determined using the cDNA- and oligo-based microarrays were 0.25 and 0.20, respectively.

Conclusion

Significant correlations were found in one third of the examined RNA species and corresponding proteins. These results suggest that RNA profiling might provide indirect support to antibodies' specificity, since whenever a evident correlation between the RNA and protein profiles exists, this can sustain that the antibodies used in the immunoassay recognized their cognate antigens.
Multiple displacement amplification for complex mixtures of DNA fragments
Authors: Shoaib Muhammad , Baconnais Sonia , Mechold Undine , Le Cam Eric , Lipinski Marc , Ogryzko Vasily
Published: August 2009

Background

A fundamental requirement for genomic studies is the availability of genetic material of good quality and quantity. The desired quantity and quality are often hard to obtain when target DNA is composed of complex mixtures of relatively short DNA fragments. Here, we sought to develop a method to representatively amplify such complex mixtures by converting them to long linear and circular concatamers, from minute amounts of starting material, followed by phi29-based multiple displacement amplification.

Results

We report here proportional amplification of DNA fragments that were first converted into concatamers starting from DNA amounts as low as 1 pg. Religations at low concentration (< 1 ng/μL) preferentially lead to fragment self-circularization, which are then amplified independently, and result in non-uniform amplification. To circumvent this problem, an additional (stuffer) DNA was added during religation (religation concentration > 10 ng/μL), which helped in the formation of long concatamers and hence resulted in uniform amplification. To confirm its usefulness in research, DP1 bound chromatin was isolated through ChIP and presence of DHFR promoter was detected using q-PCR and compared with an irrelevant GAPDH promoter. The results clearly indicated that when ChIP material was religated in presence of stuffer DNA (improved MDA), it allowed to recover the original pattern, while standard MDA and MDA without stuffer DNA failed to do so.

Conclusion

We believe that this method allows for generation of abundant amounts of good quality genetic material from a complex mixture of short DNA fragments, which can be further used in high throughput genetic analysis.
Annotation of mammalian primary microRNAs
Authors: Saini Harpreet K , Enright Anton J , Griffiths-Jones Sam
Published: August 2009

Background

MicroRNAs (miRNAs) are important regulators of gene expression and have been implicated in development, differentiation and pathogenesis. Hundreds of miRNAs have been discovered in mammalian genomes. Approximately 50% of mammalian miRNAs are expressed from introns of protein-coding genes; the primary transcript (pri-miRNA) is therefore assumed to be the host transcript. However, very little is known about the structure of pri-miRNAs expressed from intergenic regions. Here we annotate transcript boundaries of miRNAs in human, mouse and rat genomes using various transcription features. The 5' end of the pri-miRNA is predicted from transcription start sites, CpG islands and 5' CAGE tags mapped in the upstream flanking region surrounding the precursor miRNA (pre-miRNA). The 3' end of the pri-miRNA is predicted based on the mapping of polyA signals, and supported by cDNA/EST and ditags data. The predicted pri-miRNAs are also analyzed for promoter and insulator-associated regulatory regions.

Results

We define sets of conserved and non-conserved human, mouse and rat pre-miRNAs using bidirectional BLAST and synteny analysis. Transcription features in their flanking regions are used to demarcate the 5' and 3' boundaries of the pri-miRNAs. The lengths and boundaries of primary transcripts are highly conserved between orthologous miRNAs. A significant fraction of pri-miRNAs have lengths between 1 and 10 kb, with very few introns. We annotate a total of 59 pri-miRNA structures, which include 82 pre-miRNAs. 36 pri-miRNAs are conserved in all 3 species. In total, 18 of the confidently annotated transcripts express more than one pre-miRNA. The upstream regions of 54% of the predicted pri-miRNAs are found to be associated with promoter and insulator regulatory sequences.

Conclusion

Little is known about the primary transcripts of intergenic miRNAs. Using comparative data, we are able to identify the boundaries of a significant proportion of human, mouse and rat pri-miRNAs. We confidently predict the transcripts including a total of 77, 58 and 47 human, mouse and rat pre-miRNAs respectively. Our computational annotations provide a basis for subsequent experimental validation of predicted pri-miRNAs.
Genetic characterization of clinical and agri-food isolates of multi drug resistant Salmonella enterica serovar Heidelberg from Canada
Authors: Andrysiak Ashleigh K , Olson Adam B , Tracz Dobryan M , Dore Kathryn , Irwin Rebecca , Ng Lai-King , Gilmour Matthew W ,   Canadian Integrated Program for Antimicrobial Resistance Surveillance Collaborative
Published: August 2009

Background

Salmonella enterica serovar Heidelberg ranks amongst the most prevalent causes of human salmonellosis in Canada and an increase in resistance to extended spectrum cephalosporins (ESC) has been observed by the Canadian Integrated Program for Antimicrobial Resistance Surveillance. This study examined the genetic relationship between S. Heidelberg isolates from livestock, abattoir, retail meat, and clinical human specimens to determine whether there was a link between the emergence of MDR S. Heidelberg in chicken agri-food sources and the simultaneous increase of MDR S. Heidelberg in human clinical samples.

Results

Chromosomal genetic homogeneity was observed by pulsed-field gel electrophoresis (PFGE), DNA sequence-based typing (SBT) and DNA microarray-based comparative genomic hybridization (CGH). Sixty one percent of isolates were indistinguishable by PFGE conducted using Xba I and Bln I restriction enzymes. An additional 15% of isolates had PFGE patterns that were closely related to the main cluster. SBT did not identify DNA polymorphisms and CGH revealed only genetic differences between the reference S. Typhimurium strain and S. Heidelberg isolates. Genetic variation observed by CGH between S. Heidelberg isolates could be attributed to experimental variation. Alternatively, plasmid content was responsible for differences in antimicrobial susceptibility, and restriction fragment length polymorphism (RFLP) analyses followed by replicon typing identified two divergent plasmid types responsible for ESC resistance.

Conclusion

Due to the overall limited genetic diversity among the isolates, it was not possible to identify variable traits that would be suitable for source tracking between human and agri-food isolates of S. Heidelberg in Canada.
Quantitative proteomics of nutrient limitation in the hydrogenotrophic methanogen Methanococcus maripaludis
Authors: Xia Qiangwei , Wang Tiansong , Hendrickson Erik L , Lie Thomas J , Hackett Murray , Leigh John A
Published: August 2009

Background

Methanogenic Archaea play key metabolic roles in anaerobic ecosystems, where they use H2 and other substrates to produce methane. Methanococcus maripaludis is a model for studies of the global response to nutrient limitations.

Results

We used high-coverage quantitative proteomics to determine the response of M. maripaludis to growth-limiting levels of H2, nitrogen, and phosphate. Six to ten percent of the proteome changed significantly with each nutrient limitation. H2 limitation increased the abundance of a wide variety of proteins involved in methanogenesis. However, one protein involved in methanogenesis decreased: a low-affinity [Fe] hydrogenase, which may dominate over a higher-affinity mechanism when H2 is abundant. Nitrogen limitation increased known nitrogen assimilation proteins. In addition, the increased abundance of molybdate transport proteins suggested they function for nitrogen fixation. An apparent regulon governed by the euryarchaeal nitrogen regulator NrpR is discussed. Phosphate limitation increased the abundance of three different sets of proteins, suggesting that all three function in phosphate transport.

Conclusion

The global proteomic response of M. maripaludis to each nutrient limitation suggests a wider response than previously appreciated. The results give new insight into the function of several proteins, as well as providing information that should contribute to the formulation of a regulatory network model.
Virus variation resources at the National Center for Biotechnology Information: dengue virus
Authors: Resch Wolfgang , Zaslavsky Leonid , Kiryutin Boris , Rozanov Michael , Bao Yiming , Tatusova Tatiana A
Published: August 2009

Background

There is an increasing number of complete and incomplete virus genome sequences available in public databases. This large body of sequence data harbors information about epidemiology, phylogeny, and virulence. Several specialized databases, such as the NCBI Influenza Virus Resource or the Los Alamos HIV database, offer sophisticated query interfaces along with integrated exploratory data analysis tools for individual virus species to facilitate extracting this information. Thus far, there has not been a comprehensive database for dengue virus, a significant public health threat.

Results

We have created an integrated web resource for dengue virus. The technology developed for the NCBI Influenza Virus Resource has been extended to process non-segmented dengue virus genomes. In order to allow efficient processing of the dengue genome, which is large in comparison with individual influenza segments, we developed an offline pre-alignment procedure which generates a multiple sequence alignment of all dengue sequences. The pre-calculated alignment is then used to rapidly create alignments of sequence subsets in response to user queries. This improvement in technology will also facilitate the incorporation of additional virus species in the future. The set of virus-specific databases at NCBI, which will be referred to as Virus Variation Resources (VVR), allow users to build complex queries against virus-specific databases and then apply exploratory data analysis tools to the results. The metadata is automatically collected where possible, and extended with data extracted from the literature.

Conclusion

The NCBI Dengue Virus Resource integrates dengue sequence information with relevant metadata (sample collection time and location, disease severity, serotype, sequenced genome region) and facilitates retrieval and preliminary analysis of dengue sequences using integrated web analysis and visualization tools.
Analysis of current and alternative phenol based RNA extraction methodologies for cyanobacteria
Authors: Pinto Fernando Lopes , Thapper Anders , Sontheim Wolfgang , Lindblad Peter
Published: August 2009

Background

The validity and reproducibility of gene expression studies depend on the quality of extracted RNA and the degree of genomic DNA contamination. Cyanobacteria are gram-negative prokaryotes that synthesize chlorophyll a and carry out photosynthetic water oxidation. These organisms possess an extended array of secondary metabolites that impair cell lysis, presenting particular challenges when it comes to nucleic acid isolation. Therefore, we used the NHM5 strain of Nostoc punctiforme ATCC 29133 to compare and improve existing phenol based chemistry and procedures for RNA extraction.

Results

With this work we identify and explore strategies for improved and lower cost high quality RNA isolation from cyanobacteria. All the methods studied are suitable for RNA isolation and its use for downstream applications. We analyse different Trizol based protocols, introduce procedural changes and describe an alternative RNA extraction solution.

Conclusion

It was possible to improve purity of isolated RNA by modifying protocol procedures. Further improvements, both in RNA purity and experimental cost, were achieved by using a new extraction solution, PGTX.
Greatly attenuated experimental autoimmune encephalomyelitis in aquaporin-4 knockout mice
Authors: Li Lihua , Zhang Hua , Verkman AS
Published: August 2009

Background

The involvement of astrocyte water channel aquaporin-4 (AQP4) in autoimmune diseases of the central nervous system has been suggested following the identification of AQP4 autoantibodies in neuromyelitis optica, an inflammatory demyelinating disease.

Results

We investigated the involvement of AQP4 in disease severity in an established mouse model of experimental autoimmune encephalomyelitis (EAE) produced by immunization with myelin oligodendrocyte glycoprotein (MOG35–55) peptide. EAE was remarkably attenuated in AQP4 null mice compared to identically treated wildtype mice. Whereas most wildtype mice developed progressive tail and hindlimb paralysis, clinical signs were virtually absent in AQP4 null mice. Brain and spinal cords from AQP1 null mice showed greatly reduced mononuclear cell infiltration compared to wildtype mice, with relatively little myelin loss and axonal degeneration.

Conclusion

The reduced severity of autoimmune encephalomyelitis in AQP4 deficiency suggests AQP4 as a novel determinant in autoimmune inflammatory diseases of the central nervous system and hence a potential drug target.
Gene expression changes following extinction testing in a heroin behavioral incubation model
Authors: Kuntz-Melcavage Kara L , Brucklacher Robert M , Grigson Patricia S , Freeman Willard M , Vrana Kent E
Published: August 2009

Background

A number of gene expression studies have investigated changes induced by drug exposure, but few reports describe changes that persist following relapse. In this study, genome-wide analysis of gene expression was conducted following an extinction session (90 min) in rats that expressed behavioral incubation of heroin-seeking and goal-directed behavior. As an important modulator of goal-directed behavior, the medial prefrontal cortex (mPFC) was the target of genomic analysis. Rats were trained to self-administer heroin during 3 h daily sessions for 14 d. Following the self-administration period, rats were reintroduced to the self-administration chambers for a 90-minute extinction session in which they could seek heroin, but received none. Extinction sessions were conducted on groups after either 1 d or 14 d of drug-free enforced abstinence to demonstrate behavioral incubation.

Results

Behavioral data demonstrated incubation (increased expression) of heroin-seeking and goal-directed behavior after the 14 d abstinent period. That is, following 14 d of enforced abstinence, animals displayed heightened drug-seeking behavior when returned to the environment where they had previously received heroin. This increased drug-seeking took place despite the fact that they received no drug during this extinction session. Whole genome gene expression analysis was performed and results were confirmed by quantitative real-time PCR (RT-qPCR). Microarrays identified 66 genes whose expression was identified as changed by at least 1.4 fold (p < 0.02) following 14 d of abstinence and the 90-minute extinction session compared to the saline treated controls. Orthogonal confirmation by RT-qPCR demonstrated significant alterations in bdnf, calb1, dusp5, dusp6, egr1, npy, rgs2.

Conclusion

Ontological analysis indicates that several of the genes confirmed to be changed are important for neuroplasticity, and through that role may impact learning and behavior. The importance of drug-seeking behavior and memory of previous drug-taking sessions suggest that such genes may be important for relapse. The global gene expression analysis adds to the knowledge of heroin-induced changes and further highlights similarities between heroin and other drugs of abuse.
Identification of novel light-induced genes in the suprachiasmatic nucleus
Authors: Porterfield Veronica M , Piontkivska Helen , Mintz Eric M
Published: August 2009

Background

The transmission of information about the photic environment to the circadian clock involves a complex array of neurotransmitters, receptors, and second messenger systems. Exposure of an animal to light during the subjective night initiates rapid transcription of a number of immediate-early genes in the suprachiasmatic nucleus of the hypothalamus. Some of these genes have known roles in entraining the circadian clock, while others have unknown functions. Using laser capture microscopy, microarray analysis, and quantitative real-time PCR, we performed a comprehensive screen for changes in gene expression immediately following a 30 minute light pulse in suprachiasmatic nucleus of mice.

Results

The results of the microarray screen successfully identified previously known light-induced genes as well as several novel genes that may be important in the circadian clock. Newly identified light-induced genes include early growth response 2, proviral integration site 3, growth-arrest and DNA-damage-inducible 45 beta, and TCDD-inducible poly(ADP-ribose) polymerase. Comparative analysis of promoter sequences revealed the presence of evolutionarily conserved CRE and associated TATA box elements in most of the light-induced genes, while other core clock genes generally lack this combination of promoter elements.

Conclusion

The photic signalling cascade in the suprachiasmatic nucleus activates an array of immediate-early genes, most of which have unknown functions in the circadian clock. Detected evolutionary conservation of CRE and TATA box elements in promoters of light-induced genes suggest that the functional role of these elements has likely remained the same over evolutionary time across mammalian orders.
Passive tobacco exposure may impair symptomatic improvement in patients with chronic angina undergoing enhanced external counterpulsation
Authors: Efstratiadis Stilianos , Kennard Elizabeth D , Kelsey Sheryl F , Michaels Andrew D ,   the International EECP Patient Registry-2 Investigators
Published: August 2009

Background

The adverse effects of tobacco abuse on cardiovascular outcomes are well-known. However, the impact of passive smoke exposure on angina status and therapeutic response is less well-established. We examined the impact of second-hand smoke (SHS) exposure on symptomatic improvement in patients with chronic ischemic coronary disease undergoing enhanced external counterpulsation (EECP).

Methods

This observational study included 1,026 non-smokers (108 exposed and 918 not-exposed to SHS) from the Second International EECP Patient Registry. We also assessed angina response in 363 current smokers. Patient demographics, symptomatic improvement and quality of life assessment were determined by self-report prior and after EECP treatment.

Results

Non-smoking SHS subjects had a lower prevalence of prior revascularization (85% vs 90%), and had an increased prevalence of stroke (13% vs 7%) and prior smoking (72% vs 61%; all p < 0.05) compared to non-smokers without SHS exposure. Despite comparable degrees of coronary disease, baseline angina class, medical regimens and side effects during EECP, fewer SHS non-smokers completed a full 35-hour treatment course (77% vs 85%, p = 0.020) compared to non-smokers without SHS. Compared to non-smokers without SHS, non-smoking SHS subjects had less angina relief after EECP (angina class decreased ≥ 1 class: 68% vs 79%; p = 0.0082), both higher than that achieved in current smokers (66%). By multivariable logistic regression, SHS exposure was an independent predictor of failure to symptomatic improvement after EECP among non-smokers (OR 1.81, 95% confidence intervals 1.16–2.83).

Conclusion

Non-smokers with SHS exposure had an attenuated improvement in anginal symptoms compared to those without SHS following EECP.
Lewy bodies and neuronal loss in subcortical areas and disability in non-demented older people: a population based neuropathological cohort study
Authors: Byford M , Brayne C , McKeith I , Chatfield M , Ince PG , Matthews FE ,   MRC CFAS Neuropathology group
Published: August 2009

Background

Functional disability, the loss of ability to carry out daily tasks unaided, is a major adverse outcome more common with increasing age. The potential contribution of neuropathological changes in subcortical areas of the brain associated with normal ageing may be a contributing factor to this loss of function. This study investigates the clinicopathological relationship between functional ability during life and pathological correlates identified at post mortem in an UK population of older people (66–102 years).

The aim is to examine the clinicopathological correlates of functional disability in subcortical neuronal populations of non-demented elderly individuals.

Methods

156 non-demented participants in the brain donation programme of the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) were included in this study. Neuropathological examination was based on the CERAD protocol; pathologies of interest were amyloid plaques, neurofibrillary tangles, Lewy bodies, vascular disease and neuronal loss. Self-reported functional ability was scored according to a combined activities of daily living and instrumental activities of daily living scale.

Results

Functional disability was equally common in men and women over 65 years, and in both sexes disability was more common at older ages. Neuronal loss in several subcortical regions elevated the risk of functional disability by three-fold (95% CI 1.3–6.6). There was evidence for a relationship between Lewy bodies in the SN and functional disability.

Conclusion

Neuronal loss in subcortical regions is associated with functional disability in the older population. The causal relationships are not defined and require further investigation.
Impact of viral replication inhibition by entecavir on peripheral T lymphocyte subpopulations in chronic hepatitis B patients
Authors: You Jing , Sriplung Hutcha , Geater Alan , Chongsuvivatwong Virasakdi , Zhuang Lin , Li Yun-Li , Lei Hua , Liu Jun , Chen Hong-Ying , Tang Bao-Zhang , Huang Jun-Hua
Published: August 2009

Background

To investigate dynamic fluctuations of serum viral load and peripheral T-lymphocyte subpopulations of chronic hepatitis B patients and their correlation during entecavir therapy.

Methods

Fifty-five patients received entecavir 0.5 mg/d therapy. Serum HBV DNA load was measured by Real-Time-PCR, and the levels of peripheral T-lymphocyte subpopulations by flow cytometry biweekly, every four weeks and every eight weeks during weeks 1–12, 13–24 and 24–48, respectively. Multilevel modelling was used to analyse the relationship between these variables.

Results

Of the 55 patients, all HBeAg positive and with detectable HBV DNA, the majority (81.8%) had serum levels of HBV DNA over 107copies per milliliter. HBV viral load dropped sharply during the first two weeks. In 28 and 43 patients, the level became undetectable from week 24 and 48, respectively. Using pre-therapy level as the reference, a significant decrease in CD8+T cells and increase in CD4+T cells were found from week 12. Both parameters and CD4+/CD8+ratio steadily improved throughout the 48 weeks. Multilevel analyses showed that the level of decrement of HBV DNA was associated with the increment of T-lymphocyte activities only in the later period (4–48 week). After 4 weeks of therapy, for each log10scale decrement of HBV DNA, the percentage of CD4+lymphocyte was increased by 0.49 and that of CD8+decreased by 0.51.

Conclusion

T-lymphocyte subpopulations could be restored partially by entecavir treatment in patients with chronic hepatitis B concurrently with reduction of viremia.
Mycobacterium tuberculosis ecology in Venezuela: epidemiologic correlates of common spoligotypes and a large clonal cluster defined by MIRU-VNTR-24
Authors: Abadía Edgar , Sequera Monica , Ortega Dagmarys , Méndez María Victoria , Escalona Arnelly , Da Mata Omaira , Izarra Elix , Rojas Yeimy , Jaspe Rossana , Motiwala Alifiya S , Alland David , de Waard Jacobus , Takiff Howard E
Published: August 2009

Background

Tuberculosis remains an endemic public health problem, but the ecology of the TB strains prevalent, and their transmission, can vary by country and by region. We sought to investigate the prevalence of Mycobacterium tuberculosis strains in different regions of Venezuela. A previous study identified the most prevalent strains in Venezuela but did not show geographical distribution nor identify clonal genotypes. To better understand local strain ecology, we used spoligotyping to analyze 1298 M. tuberculosis strains isolated in Venezuela from 1997 to 2006, predominantly from two large urban centers and two geographically distinct indigenous areas, and then studied a subgroup with MIRU-VNTR 24 loci.

Results

The distribution of spoligotype families is similar to that previously reported for Venezuela and other South American countries: LAM 53%, T 10%, Haarlem 5%, S 1.9%, X 1.2%, Beijing 0.4%, and EAI 0.2%. The six most common shared types (SIT's 17, 93, 605, 42, 53, 20) accounted for 49% of the isolates and were the most common in almost all regions, but only a minority were clustered by MIRU-VNTR 24. One exception was the third most frequent overall, SIT 605, which is the most common spoligotype in the state of Carabobo but infrequent in other regions. MIRU-VNTR homogeneity suggests it is a clonal group of strains and was named the "Carabobo" genotype. Epidemiologic comparisons showed that patients with SIT 17 were younger and more likely to have had specimens positive for Acid Fast Bacilli on microscopy, and patients with SIT 53 were older and more commonly smear negative. Female TB patients tended to be younger than male patients. Patients from the high incidence, indigenous population in Delta Amacuro state were younger and had a nearly equal male:female distribution.

Conclusion

Six SIT's cause nearly half of the cases of tuberculosis in Venezuela and dominate in nearly all regions. Strains with SIT 17, the most common pattern overall may be more actively transmitted and SIT 53 strains may be less virulent and associated with reactivation of past infections in older patients. In contrast to other common spoligotypes, strains with SIT 605 form a clonal group centered in the state of Carabobo.
Trends in incidence and mortality of nasopharyngeal carcinoma over a 20–25 year period (1978/1983–2002) in Sihui and Cangwu counties in southern China
Authors: Jia Wei-Hua , Huang Qi-Hong , Liao Jian , Ye Weimin , Shugart YY , Liu Qing , Chen Li-Zhen , Li Yan-Hua , Lin Xiao , Wen Fa-Lin , Adami Hans-Olov , Zeng Yi , Zeng Yi-Xin
Published: August 2009

Background

Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world but is common in southern China. A recent report from the Hong Kong Cancer Registry, a high-risk area for NPC in southern China, showed that incidence rate decreased by 29% for males and by 30% for females from 1980–1999, while mortality rate decreased by 43% for males and 50% for females. Changing environmental risk factors and improvements in diagnosis and treatment were speculated to be the major factors contributing to the downward trend of the incidence and mortality rates of NPC. To investigate the secular trends in different Cantonese populations with different socio-economic backgrounds and lifestyles, we report the incidences and mortality rates from two population-based cancer registries in Sihui and Cangwu counties from 1978–2002.

Methods

Incidence and mortality rates were aggregated by 5-year age groups and 5 calendar years. To adjust for the effect of difference in age composition for different periods, the total and age-specific rates of NPC incidence and mortality rate were adjusted by direct standardization according to the World Standard Population (1960). The Estimated Annual Percentage Change (EAPC) was used as an estimate of the trend.

Results

The incidence rate of NPC has remained stable during the recent two decades in Sihui and in females in Cangwu, with a slight increase observed in males in Cangwu from 17.81 to 19.76 per 100,000. The incidence rate in Sihui is 1.4–2.0 times higher during the corresponding years than in Cangwu, even though the residents of both areas are of Cantonese ethnicity. A progressive decline in mortality rate was observed in females only in Sihui, with an average reduction of 6.3% (p = 0.016) per five-year period.

Conclusion

To summarize, there is great potential to work in the area of NPC prevention and treatment in southern China to decrease NPC risk and improve survival risk rates in order to reduce M:I ratios. Future efforts on effective prevention, early detection and treatment strategies were also discussed in this paper. Furthermore, the data quality and completeness also need to be improved.
Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression
Authors: Roth Eira S , Fetzer David T , Barron Bruce J , Joseph Usha A , Gayed Isis W , Wan David Q
Published: August 2009

Background

It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis.

Methods

We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression.

Results

No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does.
The Nigerian national blindness and visual impairment survey: Rationale, objectives and detailed methodology
Authors: Dineen Brendan , Gilbert Clare E , Rabiu Mansur , Kyari Fatima , Mahdi Abdull M , Abubakar Tafida , Ezelum Christian C , Gabriel Entekume , Elhassan Elizabeth , Abiose Adenike , Faal Hannah , Jiya Jonathan Y , Ozemela Chinenyem P , Lee Pak Sang , Gudlavalleti Murthy VS
Published: August 2009

Background

Despite having the largest population in Africa, Nigeria has no accurate population based data to plan and evaluate eye care services. A national survey was undertaken to estimate the prevalence and determine the major causes of blindness and low vision. This paper presents the detailed methodology used during the survey.

Methods

A nationally representative sample of persons aged 40 years and above was selected. Children aged 10–15 years and individuals aged <10 or 16–39 years with visual impairment were also included if they lived in households with an eligible adult. All participants had their height, weight, and blood pressure measured followed by assessment of presenting visual acuity, refractokeratomery, A-scan ultrasonography, visual fields and best corrected visual acuity. Anterior and posterior segments of each eye were examined with a torch and direct ophthalmoscope. Participants with visual acuity of < = 6/12 in one or both eyes underwent detailed examination including applanation tonometry, dilated slit lamp biomicroscopy, lens grading and fundus photography. All those who had undergone cataract surgery were refracted and best corrected vision recorded. Causes of visual impairment by eye and for the individual were determined using a clinical algorithm recommended by the World Health Organization. In addition, 1 in 7 adults also underwent a complete work up as described for those with vision < = 6/12 for constructing a normative data base for Nigerians.

Discussion

The field work for the study was completed in 30 months over the period 2005–2007 and covered 305 clusters across the entire country. Concurrently persons 40+ years were examined to form a normative data base. Analysis of the data is currently underway.

Conclusion

The methodology used was robust and adequate to provide estimates on the prevalence and causes of blindness in Nigeria. The survey would also provide information on barriers to accessing services, quality of life of visually impaired individuals and also provide normative data for Nigerian eyes.