61 research outputs found
Fusing Climate Data Products using a Spatially Varying Autoencoder
Autoencoders are powerful machine learning models used to compress
information from multiple data sources. However, autoencoders, like all
artificial neural networks, are often unidentifiable and uninterpretable. This
research focuses on creating an identifiable and interpretable autoencoder that
can be used to meld and combine climate data products. The proposed autoencoder
utilizes a Bayesian statistical framework, allowing for probabilistic
interpretations while also varying spatially to capture useful spatial patterns
across the various data products. Constraints are placed on the autoencoder as
it learns patterns in the data, creating an interpretable consensus that
includes the important features from each input. We demonstrate the utility of
the autoencoder by combining information from multiple precipitation products
in High Mountain Asia.Comment: 13 pages, 7 figure
Modelling interactions of acid–base balance and respiratory status in the toxicity of metal mixtures in the American oyster Crassostrea virginica
Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Comparative Biochemistry and Physiology - Part A: Molecular & Integrative Physiology 155 (2010): 341-349, doi:10.1016/j.cbpa.2009.11.019.Heavy metals, such as copper, zinc and cadmium, represent some of the most common and
serious pollutants in coastal estuaries. In the present study, we used a combination of linear and
artificial neural network (ANN) modelling to detect and explore interactions among low-dose
mixtures of these heavy metals and their impacts on fundamental physiological processes in
tissues of the Eastern oyster, Crassostrea virginica. Animals were exposed to Cd (0.001 – 0.400
μM), Zn (0.001 – 3.059 μM) or Cu (0.002 – 0.787 μM), either alone or in combination for 1 to
27 days. We measured indicators of acid-base balance (hemolymph pH and total CO2), gas
exchange (Po2), immunocompetence (total hemocyte counts, numbers of invasive bacteria),
antioxidant status (glutathione, GSH), oxidative damage (lipid peroxidation; LPx), and metal
accumulation in the gill and the hepatopancreas. Linear analysis showed that oxidative
membrane damage from tissue accumulation of environmental metals was correlated with
impaired acid-base balance in oysters. ANN analysis revealed interactions of metals with
hemolymph acid-base chemistry in predicting oxidative damage that were not evident from
linear analyses. These results highlight the usefulness of machine learning approaches, such as
ANNs, for improving our ability to recognize and understand the effects of sub-acute exposure to
contaminant mixtures.This study was supported by NOAA’s Center of Excellence in Oceans and Human Health at HML and the National Science Foundation
Cell cycle regulation in hematopoietic stem cells
Hematopoietic stem cells (HSCs) give rise to all lineages of blood cells. Because HSCs must persist for a lifetime, the balance between their proliferation and quiescence is carefully regulated to ensure blood homeostasis while limiting cellular damage. Cell cycle regulation therefore plays a critical role in controlling HSC function during both fetal life and in the adult. The cell cycle activity of HSCs is carefully modulated by a complex interplay between cell-intrinsic mechanisms and cell-extrinsic factors produced by the microenvironment. This fine-tuned regulatory network may become altered with age, leading to aberrant HSC cell cycle regulation, degraded HSC function, and hematological malignancy
Genome-wide association study confirm major QTL for backfat fatty acid composition on SSC14 in Duroc pigs
Background: Fatty acid composition contributes importantly to meat quality and is essential to the nutritional
value of the meat. Identification of genetic factors underlying levels of fatty acids can be used to breed for pigs
with healthier meat. The aim of this study was to conduct genome-wide association studies (GWAS) to identify QTL
regions affecting fatty acid composition in backfat from the pig breeds Duroc and Landrace.
Results: Using data from the Axiom porcine 660 K array, we performed GWAS on 454 Duroc and 659 Landrace
boars for fatty acid phenotypes measured by near-infrared spectroscopy (NIRS) technology (C16:0, C16:1n-7, C18:0,
C18:1n-9, C18:2n-6, C18:3n-3, total saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty
acids). Two QTL regions on SSC4 and SSC14 were identified in Duroc for the de novo synthesized fatty acids traits,
whereas one QTL on SSC8 was detected in Landrace for C16:1n-7. The QTL region on SSC14 has been reported in
previous studies and a putative causative mutation has been suggested in the promoter region of the SCD gene.
Whole genome re-sequencing data was used for genotype imputation and to fine map the SSC14 QTL region in
Norwegian Duroc. This effort confirms the location of the QTL on this chromosome as well as suggesting other
putative candidate genes in the region. The most significant single nucleotide polymorphisms (SNPs) located on
SSC14 explain between 55 and 76% of the genetic variance and between 27 and 54% of the phenotypic variance
for the de novo synthesized fatty acid traits in Norwegian Duroc. For the QTL region on SSC8 in Landrace, the most
significant SNP explained 19% of the genetic variance and 5% of the phenotypic variance for C16:1n-7.
Conclusions: This study confirms a major QTL affecting fatty acid composition on SSC14 in Duroc, which can be
used in genetic selection to increase the level of fatty acid desaturation. The SSC14 QTL was not segregating in the
Landrace population, but another QTL on SSC8 affecting C16:1n-7 was identified and might be used to increase the
level of desaturation in meat products from this breed
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Cell cycle regulation in hematopoietic stem cells.
Hematopoietic stem cells (HSCs) give rise to all lineages of blood cells. Because HSCs must persist for a lifetime, the balance between their proliferation and quiescence is carefully regulated to ensure blood homeostasis while limiting cellular damage. Cell cycle regulation therefore plays a critical role in controlling HSC function during both fetal life and in the adult. The cell cycle activity of HSCs is carefully modulated by a complex interplay between cell-intrinsic mechanisms and cell-extrinsic factors produced by the microenvironment. This fine-tuned regulatory network may become altered with age, leading to aberrant HSC cell cycle regulation, degraded HSC function, and hematological malignancy
Shiga toxin remodels the intestinal epithelial transcriptional response to Enterohemorrhagic Escherichia coli.
Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that causes diarrheal disease and the potentially lethal hemolytic uremic syndrome. We used an infant rabbit model of EHEC infection that recapitulates many aspects of human intestinal disease to comprehensively assess colonic transcriptional responses to this pathogen. Cellular compartment-specific RNA-sequencing of intestinal tissue from animals infected with EHEC strains containing or lacking Shiga toxins (Stx) revealed that EHEC infection elicits a robust response that is dramatically shaped by Stx, particularly in epithelial cells. Many of the differences in the transcriptional responses elicited by these strains were in genes involved in immune signaling pathways, such as IL23A, and coagulation, including F3, the gene encoding Tissue Factor. RNA FISH confirmed that these elevated transcripts were found almost exclusively in epithelial cells. Collectively, these findings suggest that Stx potently remodels the host innate immune response to EHEC
An Oral Inoculation Infant Rabbit Model for Shigella Infection
Shigella species are the leading bacterial cause of diarrheal death globally. The pathogen causes bacillary dysentery, a bloody diarrheal disease characterized by damage to the colonic mucosa and is usually spread through the fecal-oral route. Small animal models of shigellosis that rely on the oral route of infection are lacking. Here, we found that orogastric inoculation of infant rabbits with S. flexneri led to a diarrheal disease and colonic pathology reminiscent of human shigellosis. Diarrhea, intestinal colonization, and pathology in this model were dependent on the S. flexneri type III secretion system and IcsA, canonical Shigella virulence factors. Thus, oral infection of infant rabbits offers a feasible model to study the pathogenesis of shigellosis and to develop and test new therapeutics.Shigella species cause diarrheal disease globally. Shigellosis is typically characterized by bloody stools and colitis with mucosal damage and is the leading bacterial cause of diarrheal death worldwide. After the pathogen is orally ingested, it invades and replicates within the colonic epithelium through mechanisms that rely on its type III secretion system (T3SS). Currently, oral infection-based small animal models to study the pathogenesis of shigellosis are lacking. Here, we found that orogastric inoculation of infant rabbits with Shigella flexneri resulted in diarrhea and colonic pathology resembling that found in human shigellosis. Fasting animals prior to S. flexneri inoculation increased the frequency of disease. The pathogen colonized the colon, where both luminal and intraepithelial foci were observed. The intraepithelial foci likely arise through S. flexneri spreading from cell to cell. Robust S. flexneri intestinal colonization, invasion of the colonic epithelium, and epithelial sloughing all required the T3SS as well as IcsA, a factor required for bacterial spreading and adhesion in vitro. Expression of the proinflammatory chemokine interleukin 8 (IL-8), detected with in situ mRNA labeling, was higher in animals infected with wild-type S. flexneri versus mutant strains deficient in icsA or T3SS, suggesting that epithelial invasion promotes expression of this chemokine. Collectively, our findings suggest that oral infection of infant rabbits offers a useful experimental model for studies of the pathogenesis of shigellosis and for testing of new therapeutics
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