Alternatives to colonoscopy for population-wide colorectal cancer screening

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IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD

Index matching between passive and active tellurite glasses for use in microstructured fiber lasers: Erbium doped lanthanum-tellurite glass

Active and passive variants of La-containing tellurite glasses have been developed with matched refractive indices. The consequences of adding lanthanum to the glass was studied through measurements of the crystallization stability, glass viscosity and the loss of unstructured fibers. Doping the glass with erbium allowed for any spectroscopic changes to be observed through measurements of the absorption and energy level lifetimes. The fluorescence emission spectra were measured at 1.5 microm and, to the best of our knowledge, for the first time in tellurite glass at 2.7 microm.Michael R. Oermann, Heike Ebendorff-Heidepriem, Yahua Li, Tze-Cheung Foo, and Tanya M. Monrohttp://www.opticsinfobase.org/abstract.cfm?URI=oe-17-18-1557

A newly-developed community microarray resource for transcriptome profiling in Brassica species enables the confirmation of Brassica-specific expressed sequences

<p>Abstract</p> <p>Background</p> <p>The <it>Brassica </it>species include an important group of crops and provide opportunities for studying the evolutionary consequences of polyploidy. They are related to <it>Arabidopsis thaliana</it>, for which the first complete plant genome sequence was obtained and their genomes show extensive, although imperfect, conserved synteny with that of <it>A. thaliana</it>. A large number of EST sequences, derived from a range of different <it>Brassica </it>species, are available in the public database, but no public microarray resource has so far been developed for these species.</p> <p>Results</p> <p>We assembled unigenes using ~800,000 EST sequences, mainly from three species: <it>B. napus</it>, <it>B. rapa </it>and <it>B. oleracea</it>. The assembly was conducted with the aim of co-assembling ESTs of orthologous genes (including homoeologous pairs of genes in <it>B. napus </it>from each of the A and C genomes), but resolving assemblies of paralogous, or paleo-homoeologous, genes (<it>i.e</it>. the genes related by the ancestral genome triplication observed in diploid <it>Brassica </it>species). 90,864 unique sequence assemblies were developed. These were incorporated into the BAC sequence annotation for the <it>Brassica rapa </it>Genome Sequencing Project, enabling the identification of cognate genomic sequences for a proportion of them. A 60-mer oligo microarray comprising 94,558 probes was developed using the unigene sequences. Gene expression was analysed in reciprocal resynthesised <it>B. napus </it>lines and the <it>B. oleracea </it>and <it>B. rapa </it>lines used to produce them. The analysis showed that significant expression could consistently be detected in leaf tissue for 35,386 unigenes. Expression was detected across all four genotypes for 27,355 unigenes, genome-specific expression patterns were observed for 7,851 unigenes and 180 unigenes displayed other classes of expression pattern. Principal component analysis (PCA) clearly resolved the individual microarray datasets for <it>B. rapa</it>, <it>B. oleracea </it>and resynthesised <it>B. napus</it>. Quantitative differences in expression were observed between the resynthesised <it>B. napus </it>lines for 98 unigenes, most of which could be classified into non-additive expression patterns, including 17 that showed cytoplasm-specific patterns. We further characterized the unigenes for which A genome-specific expression was observed and cognate genomic sequences could be identified. Ten of these unigenes were found to be <it>Brassica</it>-specific sequences, including two that originate from complex loci comprising gene clusters.</p> <p>Conclusion</p> <p>We succeeded in developing a <it>Brassica </it>community microarray resource. Although expression can be measured for the majority of unigenes across species, there were numerous probes that reported in a genome-specific manner. We anticipate that some proportion of these will represent species-specific transcripts and the remainder will be the consequence of variation of sequences within the regions represented by the array probes. Our studies demonstrated that the datasets obtained from the arrays can be used for typical analyses, including PCA and the analysis of differential expression. We have also demonstrated that <it>Brassica</it>-specific transcripts identified <it>in silico </it>in the sequence assembly of public EST database accessions are indeed reported by the array. These would not be detectable using arrays designed using <it>A. thaliana </it>sequences.</p

Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study.

BackgroundExisting evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients.Patients and methodsChemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain.ResultsNinety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022).ConclusionsWhile elevated concentrations of IL-6 and IL-1β were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes

Sequencing and analysis of the gene-rich space of cowpea

<p>Abstract</p> <p>Background</p> <p>Cowpea, <it>Vigna unguiculata </it>(L.) Walp., is one of the most important food and forage legumes in the semi-arid tropics because of its drought tolerance and ability to grow on poor quality soils. Approximately 80% of cowpea production takes place in the dry savannahs of tropical West and Central Africa, mostly by poor subsistence farmers. Despite its economic and social importance in the developing world, cowpea remains to a large extent an underexploited crop. Among the major goals of cowpea breeding and improvement programs is the stacking of desirable agronomic traits, such as disease and pest resistance and response to abiotic stresses. Implementation of marker-assisted selection and breeding programs is severely limited by a paucity of trait-linked markers and a general lack of information on gene structure and organization. With a nuclear genome size estimated at ~620 Mb, the cowpea genome is an ideal target for reduced representation sequencing.</p> <p>Results</p> <p>We report here the sequencing and analysis of the gene-rich, hypomethylated portion of the cowpea genome selectively cloned by methylation filtration (MF) technology. Over 250,000 gene-space sequence reads (GSRs) with an average length of 610 bp were generated, yielding ~160 Mb of sequence information. The GSRs were assembled, annotated by BLAST homology searches of four public protein annotation databases and four plant proteomes (<it>A. thaliana</it>, <it>M. truncatula, O. sativa</it>, and <it>P. trichocarpa</it>), and analyzed using various domain and gene modeling tools. A total of 41,260 GSR assemblies and singletons were annotated, of which 19,786 have unique GenBank accession numbers. Within the GSR dataset, 29% of the sequences were annotated using the Arabidopsis Gene Ontology (GO) with the largest categories of assigned function being catalytic activity and metabolic processes, groups that include the majority of cellular enzymes and components of amino acid, carbohydrate and lipid metabolism. A total of 5,888 GSRs had homology to genes encoding transcription factors (TFs) and transcription associated factors (TAFs) representing about 5% of the total annotated sequences in the dataset. Sixty-two (62) of the 64 well-characterized plant transcription factor (TF) gene families are represented in the cowpea GSRs, and these families are of similar size and phylogenetic organization to those characterized in other plants. The cowpea GSRs also provides a rich source of genes involved in photoperiodic control, symbiosis, and defense-related responses. Comparisons to available databases revealed that about 74% of cowpea ESTs and 70% of all legume ESTs were represented in the GSR dataset. As approximately 12% of all GSRs contain an identifiable simple-sequence repeat, the dataset is a powerful resource for the design of microsatellite markers.</p> <p>Conclusion</p> <p>The availability of extensive publicly available genomic data for cowpea, a non-model legume with significant importance in the developing world, represents a significant step forward in legume research. Not only does the gene space sequence enable the detailed analysis of gene structure, gene family organization and phylogenetic relationships within cowpea, but it also facilitates the characterization of syntenic relationships with other cultivated and model legumes, and will contribute to determining patterns of chromosomal evolution in the Leguminosae. The micro and macrosyntenic relationships detected between cowpea and other cultivated and model legumes should simplify the identification of informative markers for marker-assisted trait selection and map-based gene isolation necessary for cowpea improvement.</p

A meta-analysis on the clinical outcomes of bridge to surgery stenting versus emergency surgery in malignant left-sided colonic obstruction

Poster PresentationINTRODUCTION: Left-sided malignant colonic obstruction was conventionally managed by emergency operation until the introduction of bridge to surgery stenting (BTS stenting). Despite evidence showing superior short-term outcome, the long-term oncological safety for BTS stenting is still questionable. Large-scale comparative studies on the long-term outcomes were scarce. The aim of this meta-analysis was to compare the short-term and long-term outcomes of BTS stenting and emergency surgery for ...postprin

Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure