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- Ohno, Tomoyuki, et al.
(författare)
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Effects of BabA expression during H. pylori infection of Mongolian gerbils
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Helicobacter pylori outer membrane proteins, such as the BabA adhesin are associated with severe pathological outcome. However, the in vivo role of the BabA adhesin during long-term infection is not clear. Design and Setting: Mongolian gerbils were inoculated with the H. pylori TN2GF4 and were necropsied at 1, 3, 6, and 18 months. Main outcome measures: Bacterial clones recovered from the infected gerbils were evaluated by immunoblot for BabA expression, radioimmunoassay for Leb-binding, and bacterial binding to gastric tissue. H1 antigen expression and the increase in sialylation levels were monitored by immunohistochemistry. Results: BabA expression increased, then progressively decreased, and was completely absent by 6 months post-infection. Loss of BabA expression was caused by nucleotide changes/deletions within the babA gene that resulted in a truncated BabA. Infection with a BabA-expressing H. pylori caused severe mucosal injury, whereas infection with a BabA non-expressing strain caused only mild inflammation. In response to the infection, changes in the epithelial glycosylation pattern were observed, similar to responses observed in humans and monkeys. Conclusion: Down-regulation of BabA is probably a result of adaptation to the host response during long-term H. pylori infection. BabA expression is most likely not essential for colonisation, but for the obtained gerbil host response, which confirms the role of BabA adhesin as a virulence factor and its impact in the induction of a severe inflammatory response. The changes in glycosylation of gastric mucosa demonstrate the relevance of the Mongolian gerbil as a model for H. pylori infection and host responses.
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- Younan, Diana, et al.
(författare)
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Ambient Temperature and Externalizing Behaviors of Adolescents in Southern California : A Longitudinal Analysis
- 2016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The climate-violence relationship has been debated for over 20 years, primarily because the supportive evidence was either ecological in nature or based on cross-sectional data. We conducted an individual-level, longitudinal analysis to investigate the association between temperature and externalizing behaviors in an urban-dwelling population.Methods: Participants (N=1287) of the Risk Factors for Antisocial Behavior Study, a multi-ethnic cohort of twins/triplets living in Southern California, were examined in 2000-2012 (aged 9 to 18 years) with repeated assessments of their aggressive and delinquent behaviors by the parent-reported Child Behavior Checklist. Ambient temperature was obtained from the local Meteorological Information System, with recordings from the closest site assigned to each geocoded residence. A monthly time-series from 1990 to 2012 was constructed and aggregated in 1-, 3-, and 6-month and 1-, 2-, and 3-year averages prior to each behavioral assessment. Multilevel mixed-effects models were used to estimate the effects of temperature, adjusting for within-family/within-individual correlations and other potential confounders.Results: Statistically significant associations (all p<0.05) were found between aggression and average temperature aggregated over 6 months or longer. Increasing aggressive behaviors were associated with rising 6-month average temperatures. However, longer-term (1- to 3-year average) temperatures showed a non-linear U-shaped association, with less aggressive behaviors at moderate temperatures (15-20°C), but increasing aggression at higher or lower temperatures. No significant effects were found on delinquency.Conclusions: Our study provides the first individual-level epidemiologic evidence supporting the adverse temperature effects on aggressive human behaviors. Similar approaches to studying violent crimes may further inform the scientific debates on climate changes and violence.
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- Andersson, Alma, et al.
(författare)
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Spatial Deconvolution of HER2-positive Breast Tumors Reveals Novel Intercellular Relationships
- 2020
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In the past decades, transcriptomic studies have revolutionized cancer treatment and diagnosis. However, tumor sequencing strategies typically result in loss of spatial information, critical to understand cell interactions and their functional relevance. To address this, we investigate spatial gene expression in HER2-positive breast tumors using Spatial Transcriptomics technology. We show that expression-based clustering enables data-driven tumor annotation and assessment of intra-and interpatient heterogeneity; from which we discover shared gene signatures for immune and tumor processes. We integrate and spatially map tumor-associated types from single cell data to find: segregated epithelial cells, interactions between B and T-cells and myeloid cells, co-localization of macrophage and T-cell subsets. A model is constructed to infer presence of tertiary lymphoid structures, applicable across tissue types and technical platforms. Taken together, we combine different data modalities to define novel interactions between tumor-infiltrating cells in breast cancer and provide tools generalizing across tissues and diseases.
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- Rising, Anna, et al.
(författare)
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Artificial Spider Silk for Stem Cell Culture
- 2015
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- There is a great need for defined cell culture systems that allow expansion of human pluripotent stem cells (hPSCs) and subsequent controlled differentiation, ideally in an implantable three-dimensional (3D) matrix. Spider silk appears to be an ideal biomaterial, since it is strong, extendible, and has favorable properties when implanted in living tissues. Spiders are difficult to house and therefor methods for recombinant production of spider silk are warranted. We have developed a method for production of recombinant spider silk fibers, films and foams that are used for the design of defined and xeno-free cell culture matrices. The matrices enable long-term expansion of multiple hPSC lines and subsequent differentiation into all three germ layers in 3D. This hPSC culture method provides robust, defined, easily produced and flexible culture environments for hPSCs (1). These matrices are promising but to realize their full potential, we need to spin continuous fibers in a reproducible way. Spider silk fibers are produced from soluble spidroins under ambient conditions. The spidroins are large and highly repetitive in sequence but capped by non-repetitive N- and C-terminal domains (NT and CT). In the gland, a pH gradient, that goes from 7.6 to <5.7, is generated by active carbonic anhydrase. The terminal domains respond in opposite ways when pH is decreased from 7 to 5: Urea denaturation and temperature stability assays show that NT dimers get significantly stabilized and then lock the spidroins into multimers, while CT on the other hand is destabilized and unfolds into b-sheet amyloid fibrils, which can trigger fiber formation (2,3). There is a high pCO2 in distal parts of the gland, and a CO2 analogue interacts with buried regions in CT as determined by NMR spectroscopy. These simultaneous events constitute a novel CO2 and proton dependent lock and trigger mechanism of spider silk formation that possibly can be harnessed in biomimetic spinning of artificial spider silk. 1. Wu S, Johansson J, Damdimopoulou P, Shahsavani M, Falk A, Hovatta O, Rising A. Spider silk for xeno-free long-term self-renewal and differentiation of human pluripotent stem cells. Biomaterials. 2014 Oct;35(30):8496-502. 2. Kronqvist, N., Otikovs, M., Chmyrov, V., Chen, G., Andersson M., Nordling, K., Landreh, M., Sarr, M., Jörnvall, H, Wennmalm, S., Widengren, J., Meng, Q., Rising, A., Otzen, D., Knight, S. D., Jaudzems, K., Johansson, J. Sequential pH-driven dimerization and stabilization of the N-terminal domain enables rapid spider silk formation Nat Comm. 2014. 10(5):3254. 3. Andersson M, Chen G, Otikovs M, Landreh M, Nordling K, Kronqvist N, Westermark P, Jörnvall H, Knight S, Ridderstråle Y, Holm L, Meng Q, Jaudzems K, Chesler M, Johansson J, Rising A. Carbonic Anhydrase Generates CO2 and H+ That Drive Spider Silk Formation Via Opposite Effects on the Terminal Domains. PLoS Biol. 2014 Aug 5;12(8):e1001921
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- Saers, Markus, 1978-
(författare)
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Translation as Linear Transduction : Models and Algorithms for Efficient Learning in Statistical Machine Translation
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Automatic translation has seen tremendous progress in recent years, mainly thanks to statistical methods applied to large parallel corpora. Transductions represent a principled approach to modeling translation, but existing transduction classes are either not expressive enough to capture structural regularities between natural languages or too complex to support efficient statistical induction on a large scale. A common approach is to severely prune search over a relatively unrestricted space of transduction grammars. These restrictions are often applied at different stages in a pipeline, with the obvious drawback of committing to irrevocable decisions that should not have been made. In this thesis we will instead restrict the space of transduction grammars to a space that is less expressive, but can be efficiently searched. First, the class of linear transductions is defined and characterized. They are generated by linear transduction grammars, which represent the natural bilingual case of linear grammars, as well as the natural linear case of inversion transduction grammars (and higher order syntax-directed transduction grammars). They are recognized by zipper finite-state transducers, which are equivalent to finite-state automata with four tapes. By allowing this extra dimensionality, linear transductions can represent alignments that finite-state transductions cannot, and by keeping the mechanism free of auxiliary storage, they become much more efficient than inversion transductions. Secondly, we present an algorithm for parsing with linear transduction grammars that allows pruning. The pruning scheme imposes no restrictions a priori, but guides the search to potentially interesting parts of the search space in an informed and dynamic way. Being able to parse efficiently allows learning of stochastic linear transduction grammars through expectation maximization. All the above work would be for naught if linear transductions were too poor a reflection of the actual transduction between natural languages. We test this empirically by building systems based on the alignments imposed by the learned grammars. The conclusion is that stochastic linear inversion transduction grammars learned from observed data stand up well to the state of the art.
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