bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tropheryma whipplei
Infective Endocarditis as the Only Manifestation of Whipple's Disease
Authors: Marín Mercedes , Muñoz Patricia , Sánchez Mónica , del Rosal Marina , Rodríguez-Créixems Marta , Bouza E. 
Published: April 2007

ABSTRACT

Here we describe a case of infective endocarditis caused by
Tropheryma whipplei
in a patient with no other symptoms of Whipple's disease. The case was diagnosed using broad-range PCR and confirmed by specific PCRs. We review the cases of infective endocarditis presenting as the only manifestation of Whipple's disease reported in the literature.
THERMOACOUSTIC TOMOGRAPHY AND THE CIRCULAR RADON TRANSFORM: EXACT INVERSION FORMULA
Authors: HALTMEIER MARKUS , SCHERZER OTMAR , BURGHOLZER PETER , NUSTER ROBERT , PALTAUF GUENTHER 
Published: April 2007

Thermoacoustic computed tomography (TACT) is an emerging hybrid imaging method for non-invasive medical diagnosis and fully three-dimensional visualization of biological probes. Within this modality electromagnetic illumination is used to induce acoustic waves inside an object of interest. In this paper, we assume that a cylindrical array of line detectors is used to record the acoustical data. This leads to the mathematical problem of inverting the circular Radon transform. The circular Radon transform arises in several other up-to-date imaging modalities, such as RADAR imaging or ultrasound tomography. In this paper we prove a novel stable formula for recovering a planar function from its circular Radon transform. We apply this formula to obtain an exact three-dimensional imaging algorithm for TACT. Numerical reconstructions from real and synthetic data demonstrate the potential and robustness of our algorithm.
Brain Atrophy Is Related to Lacunar Lesions and Tissue Microstructural Changes in CADASIL
Authors: Jouvent Eric , Viswanathan Anand , Mangin Jean-François , O’Sullivan Mike , Guichard Jean-Pierre , Gschwendtner Andreas , Cumurciuc Rodica , Buffon Frédérique , Peters Nils , Pachaï Chahin , Bousser Marie-Germaine , Dichgans Martin , Chabriat Hugues 
Published: April 2007

Background and Purpose—Cerebral atrophy has been recently recognized as a key marker of disease progression in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The contribution of subcortical cerebral lesions in this process remains undetermined. The aim of this study was to investigate the relationships between cerebral volume and different types of subcortical MRI lesions in CADASIL.Methods—Demographic, clinical, and laboratory data from 147 patients with CADASIL recruited from a prospective cohort study were analyzed. Validated methods were used to determine the ratio of brain volume to intracranial cavity volume (brain parenchymal fraction [BPF]), volume of white matter hyperintensities, volume of lacunar lesions, number of cerebral microhemorrhages, and mean apparent diffusion coefficient. Associations between BPF, clinical scales, and the different subcortical MRI markers were tested.Results—BPF obtained in 129 patients was significantly associated with the Mattis dementia rating scale (P<0.0001), Mini-Mental State Examination (P=0.002), and modified Rankin scale (P<0.0001) after adjustment for age and sex. Multiple linear regression modeling showed that BPF was independently associated with mean apparent diffusion coefficient (P<0.0001), volume of lacunar lesions (P=0.004), and age (P<0.0001), accounting for 46% of the observed variance in BPF but not with volume of white matter hyperintensities or number of microhemorrhages.Conclusions—In association with age, mean apparent diffusion coefficient and volume of lacunar lesions are strong and independent MRI predictors of BPF, a key marker of cognitive and motor disability in CADASIL. These results suggest brain atrophy is related to remote and/or diffuse consequences of both lacunar lesions and widespread microstructural alterations within the brain outside lacunar lesions.
Mortality rates, life expectancy, and causes of death in people with hemophilia A or B in the United Kingdom who were not infected with HIV
Authors: Darby Sarah C. , Kan Sau Wan , Spooner Rosemary J. , Giangrande Paul L. F. , Hill Frank G. H. , Hay Charles R. M. , Lee Christine A. , Ludlam Christopher A. , Williams Michael 
Published: April 2007

Abstract
Since the 1970s, mortality in the hemophilia population has been dominated by human immunodeficiency virus (HIV) and few reports have described mortality in uninfected individuals. This study presents mortality in 6018 people with hemophilia A or B in the United Kingdom during 1977 to 1998 who were not infected with HIV, with follow-up until January 1, 2000. Given disease severity and factor inhibitor status, all-cause mortality did not differ significantly between hemophilia A and hemophilia B. In severe hemophilia, all-cause mortality did not change significantly during 1977 to 1999. During this period, it exceeded mortality in the general population by a factor of 2.69 (95% confidence interval [CI]: 2.37-3.05), and median life expectancy in severe hemophilia was 63 years. In moderate/mild hemophilia, all-cause mortality did not change significantly during 1985 to 1999, and median life expectancy was 75 years. Compared with mortality in the general population, mortality from bleeding and its consequences, and from liver diseases and Hodgkin disease, was increased, but for ischemic heart disease it was lower, at only 62% (95% CI: 51%-76%) of general population rates, and for 14 other specific causes it did not differ significantly from general population rates. There was no evidence of any death from variant Creutzfeldt-Jakob disease or from conditions that could be confused with it.
The spectrum of mutations in the PCFT gene, coding for an intestinal folate transporter, that are the basis for hereditary folate malabsorption
Authors: Zhao Rongbao , Min Sang Hee , Qiu Andong , Sakaris Antoinette , Goldberg Gary L. , Sandoval Claudio , Malatack J. Jeffrey , Rosenblatt David S. , Goldman I. David 
Published: April 2007

AbstractHereditary folate malabsorption (HFM) is a rare autosomal recessive disorder caused by impaired intestinal folate absorption and impaired folate transport into the central nervous system. Recent studies in 1 family revealed that the molecular basis for this disorder is a loss-of-function mutation in the PCFT gene encoding a proton-coupled folate transporter. The current study broadens the understanding of the spectrum of alterations in the PCFT gene associated with HFM in 5 additional patients. There was no racial, ethnic, or sex pattern. A total of 4 different homozygous mutations were detected in 4 patients; 2 heterozygous mutations were identified in the fifth patient. Mutations involved 4 of the 5 exons, all at highly conserved amino acid residues. A total of 4 of the mutated transporters resulted in a complete loss of transport function, primarily due to decreased protein stability and/or defects in membrane trafficking, while 2 of the mutated carriers manifested residual function. Folate transport at low pH was markedly impaired in transformed lymphocytes from 2 patients. These findings further substantiate the role that mutations in PCFT play in the pathogenesis of HFM and will make possible rapid diagnosis and treatment of this disorder in infants, and prenatal diagnosis in families that carry a mutated gene.
Revisiting the Krogh Principle in the post-genome era:Caenorhabditis elegansas a model system for integrative physiology research
Authors: Strange Kevin 
Published: April 2007

SUMMARYMolecular biology drove a powerful reductionist or `molecule-centric'approach to biological research in the last half of the 20th century. Reductionism is the attempt to explain complex phenomena by defining the functional properties of the individual components that comprise multi-component systems. Systems biology has emerged in the post-genome era as the successor to reductionism. In my opinion, systems biology and physiology are synonymous. Both disciplines seek to understand multi-component processes or `systems' and the underlying pathways of information flow from an organism's genes up through increasingly complex levels of organization.The physiologist and Nobel laureate August Krogh believed that there is an ideal organism in which almost every physiological problem could be studied most readily (the `Krogh Principle'). If an investigator's goal were to define a physiological process from the level of genes to the whole animal, the optimal model organism for him/her to utilize would be one that is genetically and molecularly tractable. In other words, an organism in which forward and reverse genetic analyses could be carried out readily, rapidly and economically. Non-mammalian model organisms such as Escherichia coli, Saccharomyces, Caenorhabditis elegans, Drosophila,zebrafish and the plant Arabidopsis are cornerstones of systems biology research.The nematode C. elegans provides a particularly striking example of the experimental utility of non-mammalian model organisms. The aim of this paper is to illustrate how genetic, functional genomic, molecular and physiological methods can be combined in C. elegans to develop a systems biological understanding of fundamental physiological processes common to all animals. I present examples of the experimental tools available for the study of C. elegans and discuss how we have used them to gain new insights into osmotic stress signaling in animal cells.
Functional genomics and proteomics of the cellular osmotic stress response in `non-model' organisms
Authors: Kültz Dietmar , Fiol Diego , Valkova Nelly , Gomez-Jimenez Silvia , Chan Stephanie Y. , Lee Jinoo 
Published: April 2007

SUMMARY
All organisms are adapted to well-defined extracellular salinity ranges. Osmoregulatory mechanisms spanning all levels of biological organization, from molecules to behavior, are central to salinity adaptation. Functional genomics and proteomics approaches represent powerful tools for gaining insight into the molecular basis of salinity adaptation and euryhalinity in animals. In this review, we discuss our experience in applying such tools to so-called`non-model' species, including euryhaline animals that are well-suited for studies of salinity adaptation. Suppression subtractive hybridization,RACE-PCR and mass spectrometry-driven proteomics can be used to identify genes and proteins involved in salinity adaptation or other environmental stress responses in tilapia, sharks and sponges. For protein identification in non-model species, algorithms based on sequence homology searches such as MSBLASTP2 are most powerful. Subsequent gene ontology and pathway analysis can then utilize sets of identified genes and proteins for modeling molecular mechanisms of environmental adaptation. Current limitations for proteomics in non-model species can be overcome by improving sequence coverage, N- and C-terminal sequencing and analysis of intact proteins. Dependence on information about biochemical pathways and gene ontology databases for model species represents a more severe barrier for work with non-model species. To minimize such dependence, focusing on a single biological process (rather than attempting to describe the system as a whole) is key when applying `omics'approaches to non-model organisms.
Constructing the landscape of the mammalian transcriptome
Authors: Carninci Piero 
Published: April 2007

SUMMARYThe principal route to understanding the biological significance of the genome sequence comes from discovery and characterization of that portion of the genome that is transcribed into RNA products. We now know that this`transcriptome' is unexpectedly complex and its precise definition in any one species requires multiple technical approaches and an ability to work on a very large scale. A key step is the development of technologies able to capture snapshots of the complexity of the various kinds of RNA generated by the genome. As the human, mouse and other model genome sequencing projects approach completion, considerable effort has been focused on identifying and annotating the protein-coding genes as the principal output of the genome. In pursuing this aim, several key technologies have been developed to generate large numbers and highly diverse sets of full-length cDNAs and their variants. However, the search has identified another hidden transcriptional universe comprising a wide variety of non-protein coding RNA transcripts. Despite initial scepticism, various experiments and complementary technologies have demonstrated that these RNAs are dynamically transcribed and a subset of them can act as sense–antisense RNAs, which influence the transcriptional output of the genome. Recent experimental evidence suggests that the list of non-protein coding RNAs is still largely incomplete and that transcription is substantially more complex even than currently thought.
Modelling genotype–phenotype relationships and human disease with genetic interaction networks
Authors: Lehner Ben 
Published: April 2007

SUMMARY
Probably all heritable traits, including disease susceptibility, are affected by interactions between mutations in multiple genes. We understand little, however, about how genes interact to produce phenotypes, and there is little power to detect interactions between genes in human population studies. An alternative approach towards understanding how mutations combine to produce phenotypes is to construct systematic genetic interaction networks in model organisms. Here I describe the methods that are being used to map genetic interactions in yeast and C. elegans, and the insights that these networks provide for human disease. I also discuss the mechanistic interpretation of genetic interaction networks, how genetic interactions can be used to understand gene function, and methods that have been developed to predict genetic interactions on a genome-wide scale.
Variable gene expression in eukaryotes: a network perspective
Authors: Wittkopp Patricia J. 
Published: April 2007

SUMMARYChanges in gene expression underlie phenotypic plasticity, variation within species, and phenotypic divergence between species. These expression differences arise from modulation of regulatory networks. To understand the source of expression differences, networks of interactions among genes and gene products that orchestrate gene expression must be considered. Here I review the basic structure of eukaryotic regulatory networks and discuss selected case studies that provide insight into how these networks are altered to create expression differences within and between species.
Historical reconstructions of evolving physiological complexity:O2 secretion in the eye and swimbladder of fishes
Authors: Berenbrink Michael 
Published: April 2007

SUMMARYThe ability of some fishes to inflate their compressible swimbladder with almost pure oxygen to maintain neutral buoyancy, even against the high hydrostatic pressure several thousand metres below the water surface, has fascinated physiologists for more than 200 years. This review shows how evolutionary reconstruction of the components of such a complex physiological system on a phylogenetic tree can generate new and important insights into the origin of complex phenotypes that are difficult to obtain with a purely mechanistic approach alone. Thus, it is shown that oxygen secretion first evolved in the eyes of fishes, presumably for improved oxygen supply to an avascular, metabolically active retina. Evolution of this system was facilitated by prior changes in the pH dependence of oxygen-binding characteristics of haemoglobin (the Root effect) and in the specific buffer value of haemoglobin. These changes predisposed teleost fishes for the later evolution of swimbladder oxygen secretion, which occurred at least four times independently and can be associated with increased auditory sensitivity and invasion of the deep sea in some groups. It is proposed that the increasing availability of molecular phylogenetic trees for evolutionary reconstructions may be as important for understanding physiological diversity in the postgenomic era as the increase of genomic sequence information in single model species.
The biological importance of measuring individual variation
Authors: Crawford Douglas L. , Oleksiak Marjorie F. 
Published: April 2007

SUMMARY
Functional genomics research using Fundulus heteroclitus has focused on variation among individuals because of the evolutionary importance and value of Fundulus in explaining the human condition (why individual humans are different and are affected differently by stress,disease and drugs). Among different populations and species of Fundulus, there are evolutionarily adaptive differences in gene expression. This natural variation in gene expression seems to affect cardiac metabolism because up to 81% of the variation in glucose utilization observed in isolated heart ventricles is related to specific patterns of gene expression. The surprising result from this research is that among different groups of individuals, the expression of mRNA from different metabolic pathways explains substrate-specific metabolism. For example, variation in oxidative phosphorylation mRNAs explains glucose metabolism for one group of individuals but expression of glucose metabolism genes explains this metabolism in a different group of individuals. This variation among individuals has important implications for studies using inbred strains:conclusions based on one individual or one strain will not necessarily reflect a generalized conclusion for a population or species. Finally, there are surprisingly strong positive and negative correlations among metabolic genes,both within and between pathways. These data suggest that measures of mRNA expression are meaningful, yet there is a complexity in how gene expression is related to physiological processes.
University students' emotions, interest and activities in a web‐based learning environment
Authors: Nummenmaa Minna. , Nummenmaa Lauri. 
Published: April 2007

BackgroundWithin academic settings, students experience varied emotions and interest towards learning. Although both emotions and interest can increase students' likelihood to engage in traditional learning, little is known about the influence of emotions and interest in learning activities in a web‐based learning environment (WBLE).AimsThis study examined how emotions experienced while using a WBLE, students' interest towards the course topic and interest towards web‐based learning are associated with collaborative visible and non‐collaborative invisible activities and ‘lurking’ in the WBLE.SampleParticipants were 99 Finnish university students from five web‐based courses.MethodsAll the students enrolled in the courses filled out pre‐ and post‐test questionnaires of interest, and repeatedly completed an on‐line questionnaire on emotions experienced while using the WBLE during the courses.ResultsThe fluctuation of emotional reactions was positively associated with both visible collaborative and invisible non‐collaborative activities in the WBLE. Further, interest towards the web‐based learning was positively associated with invisible activity. The results also demonstrated that students not actively participating in the collaborative activities (i.e. lurkers) had more negative emotional experiences during the courses than other students.ConclusionThe results highlight the distinct impacts that emotions and interest have on different web‐based learning activities and that they should be considered when designing web‐based courses.
Improving outcomes for COPD patients with mild‐to‐moderate anxiety and depression: A systematic review of cognitive behavioural therapy
Authors: Coventry Peter A. , Gellatly Judith L. 
Published: April 2007

Purpose Anxiety and depression are highly prevalent in patients with chronic obstructive pulmonary disease (COPD) and are associated with lower levels of self‐efficacy, impaired health status, poorer treatment outcomes and reduced survival following emergency admission. Cognitive behavioural therapy (CBT) may be effective for treating anxiety and depression in COPD patients but evidence for this is uncertain.Methods A systematic review of controlled trials that evaluated the effectiveness of CBT for treating mild‐to‐moderate anxiety or depression in adults with clinically stable COPD. Ovid electronic bibliographic databases were searched from inception to May 2006; all content held by the Cochrane Library Issue 3, 2006 was also searched.Results One small randomized controlled trial (RCT) of moderate quality showed that CBT, when given with exercise training and education, was associated with large and significant treatment effects for both anxiety (−1.39 (95% CIs −2.19, −0.59)) and depression (−0.86 (95% CIs −1.61, −0.11)). Additionally, a larger RCT of higher quality demonstrated that CBT, when given with exercise and education, was associated with large and significant treatment effects for depression (−0.76 (95% CIs −1.34, −0.17)), but not for anxiety. No other included study reported significant reductions in either anxiety or depression in COPD patients given CBT.Conclusion There is only limited evidence that CBT, when used with exercise and education, can contribute to significant reductions in anxiety and depression in COPD patients. There is scope for a well‐powered RCT to evaluate the effectiveness and acceptability of CBT among this patient population.
Ultrasensitive Densitometry Detection of Cytokines with Nanoparticle-Modified Aptamers
Authors: Li Yuan-Yuan , Zhang Chi , Li Bo-Sheng , Zhao Li-Fan , Li Xiao-bo , Yang Wen-Jie , Xu Shun-Qing 
Published: April 2007

AbstractBackground: Aptamers mimic properties of antibodies and sometimes turn out to be even better than antibodies as reagents for assays. We describe the establishment of an ultrasensitive densitometry method for cytokine detection by nanoparticle (NP)-modified aptamers.Methods: The assay simultaneously uses a gold NP–modified aptamer and a biotin-modified aptamer to bind to the target protein, forming a sandwich complex. The absorbance signal generated by the aptamer-protein complex is amplified and detected with a microplate reader.Results: The assay for platelet-derived growth factor B-chain homodimer (PDGF-BB) was linear from 1 fmol/L to 100 pmol/L (R2 = 0.9869). The analytical detection limit was 83 amol/L. The intraassay and interassay imprecision (CVs) was ≤7.5%. Serum concentrations of PDGF-BB determined with the gold NP–modified aptamer assay and with ELISA were not significantly different.Conclusions: The gold NP–modified aptamer assay provides a fast, convenient method for cytokine detection and improves the detection range and the detection limit compared with ELISA.
Quantitative Mitochondrial DNA Mutation Analysis by Denaturing HPLC
Authors: Lim Kok Seong , Naviaux Robert K , Haas Richard H 
Published: April 2007

AbstractBackground: In recent years, denaturing HPLC (DHPLC) has been widely used to screen the whole mitochondrial genome or specific regions of the genome for DNA mutations. The quantification and mathematical modeling of DHPLC results is, however, underexplored.Methods: We generated site-directed mutants containing some common mutations in the mitochondrial DNA (mtDNA) tRNA(leu) region with different mutation loads and used PCR to amplify the gene segment of interest in these mutants. We then performed restriction digestion followed by slow reannealing to induce heteroduplex formation and analyzed the samples by use of DHPLC.Results: We observed a quadratic relationship between the heteroduplex peak areas and mutant loads, consistent with the kinetics of heteroduplex formation reported by others. This was modeled mathematically and used to quantify mtDNA mutation load. The method was able to detect a mutation present in a concentration as low as 1% and gave reproducible measurements of the mutations in the range of 2.5%–97.5%.Conclusion: The quantitative DHPLC assay is well suited for simultaneous detection and quantification of DNA mutations.