| 1. |
- Kalkunte, Satyan S., et al.
(författare)
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Transthyretin Is Dysregulated in Preeclampsia, and Its Native Form Prevents the Onset of Disease in a Preclinical Mouse Model
- 2013
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Ingår i: American Journal of Pathology. - : ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA. - 0002-9440 .- 1525-2191. ; 183:5, s. 1425-1436
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is a major pregnancy complication with potential short- and long-term consequences for both mother and fetus. Understanding its pathogenesis and causative biomarkers is likely to yield insights for prediction and treatment. Herein, we provide evidence that transthyretin, a transporter of thyroxine and retinal, is aggregated in preeclampsia and is present at reduced levels in sera of preeclamptic women, as detected by proteomic screen. We demonstrate that transthyretin aggregates form deposits in preeclampsia placental tissue and cause apoptosis. By using in vitro approaches and a humanized mouse model, we provide evidence for a causal link between dysregulated transthyretin and preeclampsia. Native transthyretin inhibits all preeclampsia-like features in the humanized mouse model, including new-onset proteinuria, increased blood pressure, glomerular endotheliosis, and production of anti-angiogenic factors. Our findings suggest that a focus on transthyretin structure and function is a novel strategy to understand and combat preeclampsia.
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| 2. |
- van Es, Michael A, et al.
(författare)
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Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis
- 2011
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Ingår i: Annals of Neurology. - : Wiley-Blackwell. - 0364-5134 .- 1531-8249. ; 70:6, s. 964-973
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD.METHODS: We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios.RESULTS: Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10(-6) for ALS and p = 4.3 × 10(-5) for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD.INTERPRETATION: The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.
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| 3. |
- Acatauassu, Diogo, et al.
(författare)
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Simple and Causal Copper Cable Model Suitable for G.fast Frequencies
- 2014
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Ingår i: IEEE Transactions on Communications. - 0090-6778. ; 62:11, s. 4040-4051
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Tidskriftsartikel (refereegranskat)abstract
- G.fast is a new standard from the International Telecommunication Union, which targets 1 Gb/s over short copper loops using frequencies up to 212 MHz. This new technology requires accurate parametric cable models for simulation, design, and performance evaluation tests. Some existing copper cable models were designed for the very high speed digital subscriber line spectra, i.e., frequencies up to 30 MHz, and adopt assumptions that are violated when the frequency range is extended to G.fast frequencies. This paper introduces a simple and causal cable model that is able to accurately characterize copper loops composed by single or multiple segments, in both frequency and time domains. Results using G.fast topologies show that, apart from being accurate, the new model is attractive due to its low computational cost and closed-form expressions for fitting its parameters to measurement data.
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| 4. |
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| 5. |
- Arking, D. E., et al.
(författare)
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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- 2014
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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| 6. |
- Berg, Ina, 1982-, et al.
(författare)
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Efficient imaging of amyloid deposits in Drosophila models of human amyloidoses
- 2010
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Ingår i: Nature Protocols. - : Macmillan Publishers Ltd.. - 1754-2189 .- 1750-2799. ; 5:5, s. 935-944
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Tidskriftsartikel (refereegranskat)abstract
- Drosophila melanogaster is emerging as an important model system for neurodegenerative disease research. In this protocol, we describe an efficient method for imaging amyloid deposits in the Drosophila brain, by the use of a luminescent-conjugated oligothiophene (lco), p-Ftaa polymer probe. We also demonstrate the feasibility of co-staining with antibodies and compare the lco staining with standard amyloid-specific probes. the lco protocol enables high-resolution imaging of several different protein aggregates, such as aβ1-42, aβ1-42e22G, transthyretin V30M and human tau, in the Drosophila brain. aβ and tau aggregates could also be distinguished from each other because of distinct lco emission spectra. Furthermore, this protocol enables threedimensional brain mapping of amyloid distribution in whole-mount Drosophila brains. the use of p-Ftaa combined with other probes, antibodies and/or dyes will aid the rapid characterization of various amyloid deposits in the rapidly growing number of Drosophila models of neurodegenerative diseases.
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| 7. |
- Berg, Ina, 1982-
(författare)
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Modeling Amyloid Disease in Drosophila melanogaster
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Amyloid diseases are caused by protein misfolding and aggregation. To date there are 27 known proteins causing amyloid disorders involving brain and peripheral protein deposition. The proteins involved in this mechanism do not share sequence homology, but the amyloid fibrils share biophysical properties and possibly a common pathogenic mechanism. Amyloid deposits are known to be involved in a broad range of neurodegenerative diseases, such as Alzheimer’s disease and Creutzfeldt-Jakob disease, as well as in non-neuropathic diseases, such as senile systemic amyloidosis and type II diabetes.During the last decade the fruit fly, Drosophila melanogaster (Drosophila), have increasingly been used as a model for neurodegenerative disease, such as Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and familial amyloidotic polyneuropathy. The advantages of using the Drosophila model are the well-defined genetic characteristics, the quantity, short life span, simplicity in genetic manipulation and the powerful binary UAS-Gal4 transgenic system. The UAS-Gal4 system allows for rapid generation of individual strains in which expression of a specific gene of interest can be directed to different tissues or cell types. The system allows the target gene to be activated in different cell- and tissue-types by altering the activator-expressing lines.This thesis has been focused on modeling amyloid diseases in Drosophila. This has been performed by:Creating new model systems of senile systemic amyloidosis and familial amyloidotic polyneuropathy in DrosophilaDeveloping a new staining protocol for detection of amyloid in DrosophilaInitiate a compound screen of Alzheimer’s disease modeled in Drosophila
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| 8. |
- Berg, Marcus, 1973-, et al.
(författare)
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Growth Histories in Bimetric Massive Gravity
- 2012
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Ingår i: Journal of Cosmology and Astroparticle Physics. - Bristol : Institute of Physics (IOP). - 1475-7516. ; :12
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Tidskriftsartikel (refereegranskat)abstract
- We perform cosmological perturbation theory in Hassan-Rosen bimetric gravity for general homogeneous and isotropic backgrounds. In the de Sitter approximation, we obtain decoupled sets of massless and massive scalar gravitational fluctuations. Matter perturbations then evolve like in Einstein gravity. We perturb the future de Sitter regime by the ratio of matter to dark energy, producing quasi-de Sitter space. In this more general setting the massive and massless fluctuations mix. We argue that in the quasi-de Sitter regime, the growth of structure in bimetric gravity differs from that of Einstein gravity.
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| 9. |
- Berg, Marcus, 1973-, et al.
(författare)
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Towards the One-loop Kahler Metric of Calabi-Yau Orientifolds
- 2014
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Ingår i: Journal of High Energy Physics (JHEP). - New York : Springer. - 1126-6708 .- 1029-8479. ; 12, s. 077-
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Tidskriftsartikel (refereegranskat)abstract
- We evaluate string one-loop contributions to the Kahler metric of closed string moduli in toroidal minimally supersymmetric (Calabi-Yau) orientifolds with D-branes. We focus on the poorly understood N = 1 sectors that receive contributions from all massive string states.
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| 10. |
- Berg, Marcus, et al.
(författare)
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Two-field high-scale inflation in a sub-Planckian region of field space
- 2010
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Ingår i: Physical Review D. Particles and fields. - 0556-2821 .- 1089-4918. ; 81:10
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Tidskriftsartikel (refereegranskat)abstract
- We present a simple two-field model of inflation and show how to embed it in string theory as a straightforward generalization of axion monodromy models. Phenomenologically, the predictions are equivalent to those of chaotic inflation, and, in particular, include observably large tensor modes. The whole high-scale large-field inflationary dynamics takes place within a region of field space that is parametrically sub-Planckian in diameter, hence improving our ability to control quantum corrections and achieve slow-roll inflation.
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