2,207 research outputs found
RNA-seq transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis
Bovine tuberculosis, caused by infection with Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including gene expression microarrays and RNA-sequencing (RNA-seq), has enabled detailed analysis of the host transcriptome to M. bovis infection, particularly at the macrophage and peripheral blood level. In the present study, we have analyzed the peripheral blood leukocyte (PBL) transcriptome of eight natural M. bovis-infected and eight age- and sex-matched non-infected control Holstein-Friesian animals using RNA-seq. In addition, we compared gene expression profiles generated using RNA-seq with those previously generated using the high-density Affymetrix(®) GeneChip(®) Bovine Genome Array platform from the same PBL-extracted RNA. A total of 3,250 differentially expressed (DE) annotated genes were detected in the M. bovis-infected samples relative to the controls (adjusted P-value ≤0.05), with the number of genes displaying decreased relative expression (1,671) exceeding those with increased relative expression (1,579). Ingenuity(®) Systems Pathway Analysis (IPA) of all DE genes revealed enrichment for genes with immune function. Notably, transcriptional suppression was observed among several of the top-ranking canonical pathways including Leukocyte Extravasation Signaling. Comparative platform analysis demonstrated that RNA-seq detected a larger number of annotated DE genes (3,250) relative to the microarray (1,398), of which 917 genes were common to both technologies and displayed the same direction of expression. Finally, we show that RNA-seq had an increased dynamic range compared to the microarray for estimating differential gene expression
Whole-transcriptome, high-throughput RNA sequence analysis of the bovine macrophage response to Mycobacterium bovis infection in vitro
BACKGROUND: Mycobacterium bovis, the causative agent of bovine tuberculosis, is an intracellular pathogen that can persist inside host macrophages during infection via a diverse range of mechanisms that subvert the host immune response. In the current study, we have analysed and compared the transcriptomes of M. bovis-infected monocyte-derived macrophages (MDM) purified from six Holstein-Friesian females with the transcriptomes of non-infected control MDM from the same animals over a 24 h period using strand-specific RNA sequencing (RNA-seq). In addition, we compare gene expression profiles generated using RNA-seq with those previously generated by us using the high-density Affymetrix® GeneChip® Bovine Genome Array platform from the same MDM-extracted RNA. RESULTS: A mean of 7.2 million reads from each MDM sample mapped uniquely and unambiguously to single Bos taurus reference genome locations. Analysis of these mapped reads showed 2,584 genes (1,392 upregulated; 1,192 downregulated) and 757 putative natural antisense transcripts (558 upregulated; 119 downregulated) that were differentially expressed based on sense and antisense strand data, respectively (adjusted P-value ≤ 0.05). Of the differentially expressed genes, 694 were common to both the sense and antisense data sets, with the direction of expression (i.e. up- or downregulation) positively correlated for 693 genes and negatively correlated for the remaining gene. Gene ontology analysis of the differentially expressed genes revealed an enrichment of immune, apoptotic and cell signalling genes. Notably, the number of differentially expressed genes identified from RNA-seq sense strand analysis was greater than the number of differentially expressed genes detected from microarray analysis (2,584 genes versus 2,015 genes). Furthermore, our data reveal a greater dynamic range in the detection and quantification of gene transcripts for RNA-seq compared to microarray technology. CONCLUSIONS: This study highlights the value of RNA-seq in identifying novel immunomodulatory mechanisms that underlie host-mycobacterial pathogen interactions during infection, including possible complex post-transcriptional regulation of host gene expression involving antisense RNA
Direct observation of molecular cooperativity near the glass transition
We describe direct observations of molecular cooperativity near the glass
transition in poly-vinyl-acetate (PVAc), through nanometer-scale probing of
dielectric fluctuations. Molecular clusters switched spontaneously between two
to four distinct configurations, producing complex random-telegraph-signals
(RTS). Analysis of the RTS and their power spectra shows that individual
clusters exhibit both transient dynamical heterogeneity and non-exponential
kinetics.Comment: 14 pages pdf, need Acrobat Reade
Mind before matter: reversing the arrow of fundamentality
In this contribution to FQXi's essay contest 2018, I suggest that it is
sometimes a step forward to reverse our intuition on "what is fundamental", a
move that is somewhat reminiscent of the idea of noncommutative geometry. I
argue that some foundational conceptual problems in physics and related fields
motivate us to attempt such a reversal of perspective, and to take seriously
the idea that an information-theoretic notion of observer ("mind") could in
some sense be more fundamental than our intuitive idea of a physical world
("matter"). I sketch what such an approach could look like, and why it would
complement but not contradict the view that the material world is the cause of
our experience.Comment: Contribution to the 2018 FQXi essay contest "What is fundamental?
Physical activity types and atrial fibrillation risk in the middle-aged and elderly: The Rotterdam Study
Background: The association between physical activity and atrial fibrillation remains controversial. Physical activity has been associated with a higher and lower atrial fibrillation risk. These inconsistent results might be related to the type of physical activity. We aimed to investigate the association of total and types of physical activity, including walking, cycling, domestic work, gardening and sports, with atrial fibrillation. Design: Prospective cohort study. Methods: Our study was performed in the Rotterdam Study, a prospective population-based cohort. We included 7018 participants aged 55 years and older with information on physical activity between 1997–2001. Cox proportional hazards models were used to examine the association of physical activity with atrial fibrillation risk. Models were adjusted for biological and behavioural risk factors and the remaining physical activity types. Physical activity was categorised in te
The Effective Lagrangian for Bulk Fermions in Models with Extra Dimensions
We compute the dimension 6 effective Lagrangian arising from the tree level
integration of an arbitrary number of bulk fermions in models with warped extra
dimensions. The coefficients of the effective operators are written in terms of
simple integrals of the metric and are valid for arbitrary warp factors, with
or without an infrared brane, and for a general Higgs profile. All relevant
tree level fermion effects in electroweak and flavor observables can be
computed using this effective Lagrangian.Comment: 22 pages. V2: typos corrected, matches published versio
Low Scale Flavor Gauge Symmetries
We study the possibility of gauging the Standard Model flavor group. Anomaly
cancellation leads to the addition of fermions whose mass is inversely
proportional to the known fermion masses. In this case all flavor violating
effects turn out to be controlled roughly by the Standard Model Yukawa,
suppressing transitions for the light generations. Due to the inverted
hierarchy the scale of new gauge flavor bosons could be as low as the
electroweak scale without violating any existing bound but accessible at the
Tevatron and the LHC. The mechanism of flavor protection potentially provides
an alternative to Minimal Flavor Violation, with flavor violating effects
suppressed by hierarchy of scales rather than couplings.Comment: 24 pages + appendices; v2) Refs. added and numerical examples
improved. Results unchanged; v3) small typos in appendix B correcte
Diversification dynamics of freshwater bivalves (Unionidae: Parreysiinae: Coelaturini) indicate historic hydrographic connections throughout the East African Rift System
Invertebrates are exceptionally diverse, but many are in decline because of anthropogenic changes to their habitat. This situation is particularly problematic for taxa that are not well monitored or taxonomically poorly understood, because the lack of knowledge hampers conservation. Despite their important functional role in freshwater ecosystems, African bivalves of the family Unionidae remain poorly studied compared to their highly threatened relatives in Europe, the U.S.A. and Canada. To resolve relationships and to study diversification dynamics in space and time, we performed time-calibrated phylogenetic studies and biogeographical modeling on the unionids from the East African Rift System and surroundings, including representatives of all currently recognized Afrotropical genera except for Brazzaea (and Unio from southern Africa). Our analyses indicate that all sampled Afrotropical unionids belong to the tribe Coelaturini (subfamily Parreysiinae), as does the genus Moncetia from Lake Tanganyika, which is currently attributed to the family Iridinidae. Colonization of Africa from Eurasia by Parreysiinae occurred ~17 Ma ago, and the subsequent diversification of Coelaturini in Africa continued at a steady pace, although net diversification decreased over time as more niches and ecoregions became occupied. Clades in Coelaturini largely reflect drainage basins, with the oldest lineages and highest regional diversity occurring in Lake Tanganyika, followed by the Congo Basin watershed in general. The species assemblage of Lake Tanganyika reflects multiple independent events of colonization and intralacustrine diversification since the Late Miocene or Early Pliocene. The clades of other regions, including that containing the species from Lake Malawi, are comparatively young. Biogeographical analyses indicate that the colonization history was mainly driven by cladogenesis in sympatry, whereas few anagenetic events contributed to the modern distribution of Coelaturini. Ancestral range estimations demonstrate that Coelaturini originated in the Victoria and/or Tanganyika ecoregions, and that the Congo Basin played an essential role in the colonization of Africa by Coelaturini.The attached document is the authors’ final accepted/submitted version of the journal article. You are advised to consult the publisher’s version if you wish to cite from it
Multimodality Treatment with Conventional Transcatheter Arterial Chemoembolization and Radiofrequency Ablation for Unresectable Hepatocellular Carcinoma
Background/Aims: To evaluate the efficacy of multimodality treatment consisting of conventional transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) in patients with non-resectable and non-ablatable hepatocellular carcinoma (HCC). Methods: In this retrospective study, 85 consecutive patients with HCC (59 solitary, 29 multifocal HCC) received TACE followed by RFA between 2001 and 2010. The mean number of tumors per patient was 1.6 +/- 0.7 with a mean size of 3.0 +/- 0.9 cm. Both local efficacy and patient survival were evaluated. Results: Of 120 treated HCCs, 99 (82.5%) showed a complete response (CR), while in 21 HCCs (17.5%) a partial response was depicted. Patients with solitary HCC revealed CR in 91% (51/56); in patients with multifocal HCC (n = 29) CR was achieved in 75% (48 of 64 HCCs). The median survival for all patients was 25.5 months. The 1-, 2-, 3- and 5-year survival rates were 84.6, 58.7, 37.6 and 14.6%, respectively. Statistical analysis revealed a significant difference in survival between Barcelona Clinic Liver Cancer (BCLC) A (73.4 months) and B (50.3 months) patients, while analyses failed to show a difference for Child-Pugh score, Cancer of Liver Italian Program (CLIP) score and tumor distribution pattern. Conclusion: TACE combined with RFA provides an effective treatment approach with high local tumor control rates and promising survival data, especially for BCLC A patients. Randomized trials are needed to compare this multimodality approach with a single modality approach for early-stage HCC. Copyright (C) 2011 S. Karger AG, Base
Adaptive Filtering Enhances Information Transmission in Visual Cortex
Sensory neuroscience seeks to understand how the brain encodes natural
environments. However, neural coding has largely been studied using simplified
stimuli. In order to assess whether the brain's coding strategy depend on the
stimulus ensemble, we apply a new information-theoretic method that allows
unbiased calculation of neural filters (receptive fields) from responses to
natural scenes or other complex signals with strong multipoint correlations. In
the cat primary visual cortex we compare responses to natural inputs with those
to noise inputs matched for luminance and contrast. We find that neural filters
adaptively change with the input ensemble so as to increase the information
carried by the neural response about the filtered stimulus. Adaptation affects
the spatial frequency composition of the filter, enhancing sensitivity to
under-represented frequencies in agreement with optimal encoding arguments.
Adaptation occurs over 40 s to many minutes, longer than most previously
reported forms of adaptation.Comment: 20 pages, 11 figures, includes supplementary informatio
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