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1.
Adv Funct Mater ; 34(35): 2303622, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39355087

ABSTRACT

Hydrogels are useful drug release systems and tissue engineering scaffolds. However, synthetic hydrogels often require harsh gelation conditions and can contain toxic by-products while naturally derived hydrogels can transmit pathogens and in general have poor mechanical properties. Thus, there is a need for a hydrogel that forms under ambient conditions, is non-toxic, xeno-free, and has good mechanical properties. A recombinant spider silk protein-derived hydrogel that rapidly forms at 37 °C is recently developed. The temperature and gelation times are well-suited for an injectable in situ polymerising hydrogel, as well as a 3D cell culture scaffold. Here, it is shown that the diffusion rate and the mechanical properties can be tuned by changing the protein concentration and that human fetal mesenchymal stem cells encapsulated in the hydrogels show high survival and viability. Furthermore, mixtures of recombinant spider silk proteins and green fluorescent protein (GFP) form gels from which functional GFP is gradually released, indicating that bioactive molecules are easily included in the gels, maintain activity and can diffuse through the gel. Interestingly, encapsulated ARPE-19 cells are viable and continuously produce the growth factor progranulin, which is detected in the cell culture medium over the study period of 31 days.

2.
Environ Sci Technol ; 56(13): 9593-9603, 2022 07 05.
Article in English | MEDLINE | ID: mdl-35735988

ABSTRACT

This research investigates carbon footprint impacts for full fleet electrification of Swedish passenger car travel in combination with different charging conditions, including electric road system (ERS) that enables dynamic on-road charging. The research applies a prospective life cycle analysis framework for estimating carbon footprints of vehicles, fuels, and infrastructure. The framework includes vehicle stock turnover modeling of fleet electrification and modeling of optimal battery capacity for different charging conditions based on Swedish real-world driving patterns. All new car sales are assumed to be electric after 2030 following phase-out policies for gasoline and diesel cars. Implementing ERS on selected high-traffic roads could yield significant avoided emissions in battery manufacturing compared to the additional emissions in ERS construction. ERS combined with stationary charging could enable additional reductions in the cumulative carbon footprint of about 12-24 million tons of CO2 over 30 years (2030-2060) compared to an electrified fleet only relying on stationary charging. The range depends on uncertainty in emission abatement in global manufacturing, where the lower is based on Paris Agreement compliance and the higher on current climate policies. A large share of the reduction could be achieved even if only a small share of the cars adopts the optimized battery capacities.


Subject(s)
Automobiles , Vehicle Emissions , Gasoline , Motor Vehicles , Prospective Studies , Vehicle Emissions/analysis , Vehicle Emissions/prevention & control
3.
Arterioscler Thromb Vasc Biol ; 38(8): e145-e158, 2018 08.
Article in English | MEDLINE | ID: mdl-29880490

ABSTRACT

Objective- Dyslipidemia is a component of the metabolic syndrome, an established risk factor for atherosclerotic cardiovascular disease, and is also observed in various autoimmune and chronic inflammatory conditions. However, there are limited opportunities to study the impact of acquired dyslipidemia on cardiovascular and immune pathology. Approach and Results- We designed a model system that allows for the conversion to a state of acute hyperlipidemia in adult life, so that the consequences of such a transition could be observed, through conditionally deleting APOE (apolipoprotein E) in the adult mouse. The transition to hypercholesterolemia was accompanied by adaptive immune responses, including the expansion of T lymphocyte helper cell 1, T follicular helper cell, and T regulatory subsets and the formation of germinal centers. Unlike steady-state Apoe-/- mice, abrupt loss of APOE induced rapid production of antibodies recognizing rheumatoid disease autoantigens. Genetic ablation of the germinal center reduced both autoimmunity and atherosclerosis, indicating that the immune response that follows loss of APOE is independent of atherosclerosis but nevertheless promotes plaque development. Conclusions- Our findings suggest that immune activation in response to hyperlipidemia could contribute to a wide range of inflammatory autoimmune diseases, including atherosclerosis.


Subject(s)
Adaptive Immunity , Aorta/immunology , Aortic Diseases/immunology , Apolipoproteins E/immunology , Atherosclerosis/immunology , Autoimmunity , Dyslipidemias/immunology , Inflammation/immunology , Animals , Aorta/metabolism , Aorta/pathology , Aortic Diseases/genetics , Aortic Diseases/metabolism , Aortic Diseases/pathology , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Atherosclerosis/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Cells, Cultured , Disease Models, Animal , Disease Progression , Dyslipidemias/genetics , Dyslipidemias/metabolism , Dyslipidemias/pathology , Germinal Center/immunology , Germinal Center/metabolism , Immunity, Humoral , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Mice, Inbred C57BL , Mice, Knockout, ApoE , Plaque, Atherosclerotic , Signal Transduction , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Time Factors
4.
Eur J Nutr ; 57(4): 1651-1666, 2018 Jun.
Article in English | MEDLINE | ID: mdl-28417207

ABSTRACT

PURPOSE: Rye products have been reported to elicit postprandial insulin and glucose responses which may be beneficial for prevention of type-2 diabetes. However, mechanisms underlying variations in responses related to processing techniques are not fully understood. METHODS: Five differently processed rye products (sourdough-fermented bread, fermented and unfermented crispbread, extrusion-cooked rye, and porridge) and refined wheat bread were characterised. Two in vitro methods, a dynamic method simulating digestion in the stomach and small intestine and a static method, simulating conditions in the stomach were used to determine viscosity development, structural changes and release of glucose during digestion. RESULTS: Structural and compositional differences induced by processing influenced product digestion. Gastric disintegration and digesta particle size were related to characteristics of the starch/protein matrix, while digesta viscosity was reduced due to fibre degradation during fermentation. More cohesive boluses were associated with slower glucose release. Sourdough fermentation increased amylose leakage and appeared to inhibit starch hydrolysis despite low digesta viscosity and rapid disintegration. CONCLUSIONS: The net release of glucose during digestion of foods is determined by several factors which may vary in their importance depending on product specific properties.


Subject(s)
Digestion/physiology , Food Handling , Secale/metabolism , Triticum/metabolism , Blood Glucose , Bread , Dietary Fiber , Postprandial Period , Starch
5.
Arterioscler Thromb Vasc Biol ; 36(1): 25-36, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26564818

ABSTRACT

OBJECTIVE: The V1 (VHS107.1.42) immunoglobulin heavy chain gene is thought to be critical in producing IgM natural antibodies of the T15-idiotype that protect against both atherosclerosis and infection from Streptococcus pneumoniae. Our aim was to determine whether genetic loss of the V1 gene increased atherosclerotic plaque burden in vivo because of a reduction in the T15-idiotype or other atheroprotective antibodies. APPROACH AND RESULTS: We crossed VHS107.1.42-deficient mice with the atherosclerosis-prone Apoe(-/-) and Ldlr(-/-) strains. Although these double knockout strains manifested no defects in B-cell development, we did observe a substantial reduction in early immune responses against phosphocholine after immunization. However, the titers of plasma antibodies reacting against defined atherosclerotic antigens such as oxidized low-density lipoprotein, as well as the T15-idiotype, were unaffected by loss of the VHS107.1.42 gene in hypercholesterolemic mice. Furthermore, we observed no increase in atherosclerotic lesion formation, either within the aortic arch or aortic root. Robust deposition of IgM within atherosclerotic plaques could also be readily observed in both control and experimental mice. CONCLUSIONS: Our data indicate that IgM-dependent protection against atherosclerosis is unlikely to be dependent on antibodies that use the VHS107.1.42 gene, in contrast to the acute immune response conferred by this heavy chain in the response to phosphocholine and in providing resistance against lethal S pneumoniae infection.


Subject(s)
Aortic Diseases/genetics , Atherosclerosis/genetics , Genes, Immunoglobulin Heavy Chain , Animals , Aorta/immunology , Aorta/metabolism , Aorta/pathology , Aortic Diseases/immunology , Aortic Diseases/metabolism , Aortic Diseases/pathology , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Atherosclerosis/immunology , Atherosclerosis/metabolism , Atherosclerosis/pathology , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Disease Models, Animal , Hypercholesterolemia/genetics , Hypercholesterolemia/metabolism , Immunity, Humoral , Immunoglobulin M/blood , Lipoproteins, LDL/blood , Lipoproteins, LDL/immunology , Mice, Inbred C57BL , Mice, Knockout , Phosphorylcholine/immunology , Plaque, Atherosclerotic , Receptors, LDL/genetics , Receptors, LDL/metabolism , Spleen/immunology , Spleen/metabolism
6.
Br J Nutr ; 118(9): 686-697, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29185930

ABSTRACT

Sourdough fermentation is considered to have beneficial effects on postprandial satiety and metabolic responses, but studies demonstrating effects at physiological conditions are lacking. The aim of this acute breakfast intervention study was to determine the effect of consumption of sourdough-fermented and unfermented rye crispbread on self-rated appetite, postprandial glucose and insulin response in healthy subjects. In all, twenty-four Swedish adults were included in a single-blinded, randomised cross-over trial. Three crispbreads (sourdough-fermented and unfermented whole grain rye and yeast-fermented refined wheat as control) were consumed as part of a standardised breakfast. Subjective appetite score, assessed using visual analogue scale, and plasma glucose and insulin concentrations were measured at baseline and postprandially until 360 and 240 min, respectively. Structural changes and viscosity during mastication and gastric digestion were investigated using in vitro methods. Hunger and desire to eat were lower (P<0·05) based on AUC measurements after intake of sourdough-fermented rye crispbread compared with after intake of yeast-fermented refined wheat crispbread. On the basis of AUC (0-230 min), insulin response was lowest after intake of unfermented rye crispbread compared with sourdough-fermented rye and yeast-fermented refined wheat crispbread. Degradation of viscous fibres and faster bolus disintegration for the sourdough-fermented bread may partly explain the less favourable metabolic responses compared with unfermented bread. Our results showed that food processing affects the composition and structural characteristics of rye bread, which has implications for appetite and metabolic responses.


Subject(s)
Appetite , Blood Glucose/metabolism , Bread , Fermented Foods , Postprandial Period , Secale/chemistry , Adult , Breakfast , Cross-Over Studies , Dietary Fiber/administration & dosage , Digestion , Female , Glucagon-Like Peptide 1/blood , Humans , Insulin/blood , Male , Middle Aged , Satiation , Single-Blind Method , Sweden , Triticum/chemistry , Whole Grains/chemistry , Young Adult
7.
BMC Ecol ; 17(1): 14, 2017 04 05.
Article in English | MEDLINE | ID: mdl-28381278

ABSTRACT

BACKGROUND: Establishing populations in ecologically marginal habitats may require substantial phenotypic changes that come about through phenotypic plasticity, local adaptation, or both. West-Eberhard's "plasticity-first" model suggests that plasticity allows for rapid colonisation of a new environment, followed by directional selection that develops local adaptation. Two predictions from this model are that (i) individuals of the original population have high enough plasticity to survive and reproduce in the marginal environment, and (ii) individuals of the marginal population show evidence of local adaptation. Individuals of the macroalga Fucus vesiculosus from the North Sea colonised the hyposaline (≥2-3‰) Baltic Sea less than 8000 years ago. The colonisation involved a switch from fully sexual to facultative asexual recruitment with release of adventitious branches that grow rhizoids and attach to the substratum. To test the predictions from the plasticity-first model we reciprocally transplanted F. vesiculosus from the original population (ambient salinity 24‰) and from the marginal population inside the Baltic Sea (ambient salinity 4‰). We also transplanted individuals of the Baltic endemic sister species F. radicans from 4 to 24‰. We assessed the degree of plasticity and local adaptation in growth and reproductive traits after 6 months by comparing the performance of individuals in 4 and 24‰. RESULTS: Branches of all individuals survived the 6 months period in both salinities, but grew better in their native salinity. Baltic Sea individuals more frequently developed asexual traits while North Sea individuals initiated formation of receptacles for sexual reproduction. CONCLUSIONS: Marine individuals of F. vesiculosus are highly plastic with respect to salinity and North Sea populations can survive the extreme hyposaline conditions of the Baltic Sea without selective mortality. Plasticity alone would thus allow for an initial establishment of this species inside the postglacial Baltic Sea at salinities where reproduction remains functional. Since establishment, the Baltic Sea populations have evolved adaptations to extreme hyposaline waters and have in addition evolved asexual recruitment that, however, tends to impede local adaptation. Overall, our results support the "plasticity-first" model for the initial colonisation of the Baltic Sea by Fucus vesiculosus.


Subject(s)
Fucus/physiology , Seawater/chemistry , Acclimatization , Ecosystem , Environment , Fucus/growth & development , Salinity
8.
J Gen Virol ; 96(Pt 3): 565-570, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25395591

ABSTRACT

A salmonid alphavirus (SAV) replicon has been developed to express heterologous antigens but protein production was low to modest compared with terrestrial alphavirus replicons. In this study, we have compared several modifications to a SAV replicon construct and analysed their influence on foreign gene expression. We found that an insertion of a translational enhancer consisting of the N-terminal 102 nt of the capsid gene, together with a nucleotide sequence encoding the foot-and-mouth disease virus (FMDV) 2A peptide, caused a significant increase in EGFP reporter gene expression. The importance of fusing a hammerhead (HH) ribozyme sequence at the 5' end of the viral genome was also demonstrated. In contrast, a hepatitis D virus ribozyme (HDV-RZ) sequence placed at the 3' end did not augment expression of inserted genes. Taken together, we have developed a platform for optimized antigen production, which can be applied for immunization of salmonid fish in the future.


Subject(s)
Alphavirus/genetics , Antigens, Viral/metabolism , Genetic Vectors/genetics , Replicon/genetics , Animals , Antigens, Viral/genetics , Cell Line , Cytopathogenic Effect, Viral , DNA, Complementary , DNA, Viral , Gene Expression Regulation, Viral/physiology , Genetic Vectors/physiology , Virus Cultivation
9.
J Virol ; 88(5): 2858-66, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24371047

ABSTRACT

UNLABELLED: Chikungunya virus (CHIKV) is a reemerging mosquito-borne alphavirus that has caused severe epidemics in Africa and Asia and occasionally in Europe. As of today, there is no licensed vaccine available to prevent CHIKV infection. Here we describe the development and evaluation of novel CHIKV vaccine candidates that were attenuated by deleting a large part of the gene encoding nsP3 or the entire gene encoding 6K and were administered as viral particles or infectious genomes launched by DNA. The resulting attenuated mutants were genetically stable and elicited high magnitudes of binding and neutralizing antibodies as well as strong T cell responses after a single immunization in C57BL/6 mice. Subsequent challenge with a high dose of CHIKV demonstrated that the induced antibody responses protected the animals from viremia and joint swelling. The protective antibody response was long-lived, and a second homologous immunization further enhanced immune responses. In summary, this report demonstrates a straightforward means of constructing stable and efficient attenuated CHIKV vaccine candidates that can be administered either as viral particles or as infectious genomes launched by DNA. IMPORTANCE: Similar to other infectious diseases, the best means of preventing CHIKV infection would be by vaccination using an attenuated vaccine platform which preferably raises protective immunity after a single immunization. However, the attenuated CHIKV vaccine candidates developed to date rely on a small number of attenuating point mutations and are at risk of being unstable or even sensitive to reversion. We report here the construction and preclinical evaluation of novel CHIKV vaccine candidates that have been attenuated by introducing large deletions. The resulting mutants proved to be genetically stable, attenuated, highly immunogenic, and able to confer durable immunity after a single immunization. Moreover, these mutants can be administered either as viral particles or as DNA-launched infectious genomes, enabling evaluation of the most feasible vaccine modality for a certain setting. These CHIKV mutants could represent stable and efficient vaccine candidates against CHIKV.


Subject(s)
Alphavirus Infections/immunology , Chikungunya virus/immunology , Vaccines, Attenuated/immunology , Viral Vaccines/immunology , Alphavirus Infections/prevention & control , Alphavirus Infections/virology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Chikungunya Fever , Chikungunya virus/genetics , Female , Gene Order , Genome, Viral , Immunity, Cellular , Immunization , Immunization, Secondary , Mice , Mice, Inbred C57BL , Mutation , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/genetics , Viral Proteins/genetics , Viral Proteins/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/genetics
10.
Mitig Adapt Strateg Glob Chang ; 20(8): 1335-1359, 2015.
Article in English | MEDLINE | ID: mdl-30197558

ABSTRACT

This paper presents a modeling comparison on how stabilization of global climate change at about 2 °C above the pre-industrial level could affect economic and energy systems development in China and India. Seven General Equilibrium (CGE) and energy system models on either the global or national scale are soft-linked and harmonized with respect to population and economic assumptions. We simulate a climate regime, based on long-term convergence of per capita carbon dioxide (CO2) emissions, starting from the emission pledges presented in the Copenhagen Accord to the United Nations Framework Convention on Climate Change and allowing full emissions trading between countries. Under the climate regime, Indian emission allowances are allowed to grow more than the Chinese allowances, due to the per capita convergence rule and the higher population growth in India. Economic and energy implications not only differ among the two countries, but also across model types. Decreased energy intensity is the most important abatement approach in the CGE models, while decreased carbon intensity is most important in the energy system models. The reduction in carbon intensity is mostly achieved through deployment of carbon capture and storage, renewable energy sources and nuclear energy. The economic impacts are generally higher in China than in India, due to higher 2010-2050 cumulative abatement in China and the fact that India can offset more of its abatement cost though international emission trading.

11.
Nat Genet ; 37(2): 153-9, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15640799

ABSTRACT

Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892,819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them.


Subject(s)
Francisella tularensis/genetics , Genome, Bacterial , Base Sequence , DNA Transposable Elements , Francisella tularensis/growth & development , Genomic Islands , Iron/metabolism , Molecular Sequence Data , Mutation , Sequence Analysis, DNA , Virulence/genetics
12.
J Virol ; 86(8): 4082-90, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22318135

ABSTRACT

Vaccination using "naked" DNA is a highly attractive strategy for induction of pathogen-specific immune responses; however, it has been only weakly immunogenic in humans. Previously, we constructed DNA-launched Semliki Forest virus replicons (DREP), which stimulate pattern recognition receptors and induce augmented immune responses. Also, in vivo electroporation was shown to enhance immune responses induced by conventional DNA vaccines. Here, we combine these two approaches and show that in vivo electroporation increases CD8(+) T cell responses induced by DREP and consequently decreases the DNA dose required to induce a response. The vaccines used in this study encode the multiclade HIV-1 T cell immunogen HIVconsv, which is currently being evaluated in clinical trials. Using intradermal delivery followed by electroporation, the DREP.HIVconsv DNA dose could be reduced to as low as 3.2 ng to elicit frequencies of HIV-1-specific CD8(+) T cells comparable to those induced by 1 µg of a conventional pTH.HIVconsv DNA vaccine, representing a 625-fold molar reduction in dose. Responses induced by both DREP.HIVconsv and pTH.HIVconsv were further increased by heterologous vaccine boosts employing modified vaccinia virus Ankara MVA.HIVconsv and attenuated chimpanzee adenovirus ChAdV63.HIVconsv. Using the same HIVconsv vaccines, the mouse observations were supported by an at least 20-fold-lower dose of DNA vaccine in rhesus macaques. These data point toward a strategy for overcoming the low immunogenicity of DNA vaccines in humans and strongly support further development of the DREP vaccine platform for clinical evaluation.


Subject(s)
DNA, Viral/immunology , HIV-1/immunology , Plasmids/immunology , Semliki forest virus/genetics , Semliki forest virus/immunology , T-Lymphocytes/immunology , Vaccines, DNA/immunology , AIDS Vaccines/administration & dosage , AIDS Vaccines/genetics , AIDS Vaccines/immunology , Animals , CD8-Positive T-Lymphocytes/immunology , Cell Line , DNA, Viral/genetics , Electroporation , Female , Gene Order , HIV Infections/immunology , HIV Infections/prevention & control , Humans , Macaca mulatta , Mice , Mice, Inbred BALB C , Plasmids/administration & dosage , Plasmids/genetics , Vaccines, DNA/administration & dosage , Vaccines, DNA/genetics
13.
Microb Pathog ; 55: 28-31, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23044056

ABSTRACT

Infective endocarditis (IE) is a severe infection associated with significant morbidity and mortality. Enterococcus faecalis is among the most common causes of this disease, and yet little is known about the pathogenesis of E. faecalis IE. We screened 21 E. faecalis isolates from IE and 21 isolates from normal flora for the putative virulence factors ace, asa1, gelE, and esp with PCR. In addition, we determined the ability of the isolates to form biofilm and to aggregate platelets. With the exception of biofilm formation, which was more pronounced in the normal flora group, there was no difference between the groups, indicating that many isolates have virulence properties and that host factors might determine if E. faecalis causes IE.


Subject(s)
Bacterial Proteins/metabolism , Endocarditis, Bacterial/microbiology , Enterococcus faecalis/isolation & purification , Enterococcus faecalis/pathogenicity , Intestines/microbiology , Virulence Factors/metabolism , Bacterial Proteins/genetics , Biofilms , Enterococcus faecalis/genetics , Enterococcus faecalis/physiology , Feces/microbiology , Humans , Virulence Factors/genetics
14.
Animals (Basel) ; 13(11)2023 May 27.
Article in English | MEDLINE | ID: mdl-37889740

ABSTRACT

Traditional methods for age determination of wildlife include either slicing thin sections off or grinding a tooth, both of which are laborious and invasive. Especially when it comes to ancient and valuable museum samples of rare or extinct species, non-invasive methods are preferable. In this study, X-ray micro-computed tomography (µ-CT) was verified as an alternative non-invasive method for age determination of three species within the order of Carnivora and suborders Odontoceti. Teeth from 13 red foxes (Vulpes vulpes), 2 American mink (Neogale vison), and 2 harbor porpoises (Phocoena phocoena) of known age were studied using µ-CT. The number of visible dental growth layers in the µ-CT were highly correlated with true age for all three species (R2 = 96%, p < 0.001). In addition, the Bland-Altman plot showed high agreement between the age of individuals and visible dental layers represented in 2D slices of the 3D µ-CT images. The true age of individuals was on average 0.3 (±0.6 SD) years higher than the age interpreted by the µ-CT image, and there was a 95% agreement between the true age and the age interpreted from visible dental layers in the µ-CT.

15.
bioRxiv ; 2023 May 24.
Article in English | MEDLINE | ID: mdl-37292721

ABSTRACT

The majority of the world population carry the gastric pathogen Helicobacter pylori. Fortunately, most individuals experience only low-grade or no symptoms, but in many cases the chronic inflammatory infection develops into severe gastric disease, including duodenal ulcer disease and gastric cancer. Here we report on a protective mechanism where H. pylori attachment and accompanying chronic mucosal inflammation can be reduced by antibodies that are present in a vast majority of H. pylori carriers. These antibodies block binding of the H. pylori attachment protein BabA by mimicking BabA's binding to the ABO blood group glycans in the gastric mucosa. However, many individuals demonstrate low titers of BabA blocking antibodies, which is associated with an increased risk for duodenal ulceration, suggesting a role for these antibodies in preventing gastric disease.

16.
Circulation ; 123(10): 1083-91, 2011 Mar 15.
Article in English | MEDLINE | ID: mdl-21357823

ABSTRACT

BACKGROUND: Atherosclerosis is a chronic inflammatory disease characterized by a massive intimal accumulation of low-density lipoprotein that triggers chronic vascular inflammation with an autoimmune response to low-density lipoprotein components. METHODS AND RESULTS: To dampen the inflammatory component of atherosclerosis, we injected hypercholesterolemic huB100(tg) × Ldlr(-/-) mice (mice transgenic for human apolipoprotein B100 [ApoB100] and deficient for the low-density lipoprotein receptor) intravenously with dendritic cells (DCs) that had been pulsed with the low-density lipoprotein protein ApoB100 in combination with the immunosuppressive cytokine interleukin-10. DCs treated with ApoB100 and interleukin-10 reduced proliferation of effector T cells, inhibited production of interferon-γ, and increased de novo generation of regulatory T cells in vitro. Spleen cells from mice treated with DCs plus ApoB100 plus interleukin-10 showed diminished proliferative responses to ApoB100 and significantly dampened T-helper 1 and 2 immunity to ApoB100. Spleen CD4(+) T cells from these mice suppressed activation of ApoB100-reactive T cells in a manner characteristic of regulatory T cells, and mRNA analysis of lymphoid organs showed induction of transcripts characteristic of these cells. Treatment of huB100(tg) × Ldlr(-/-) mice with ApoB100-pulsed tolerogenic DCs led to a significant (70%) reduction of atherosclerotic lesions in the aorta, with decreased CD4(+) T-cell infiltration and signs of reduced systemic inflammation. CONCLUSIONS: Tolerogenic DCs pulsed with ApoB100 reduced the autoimmune response against low-density lipoprotein and may represent a novel possibility for treatment or prevention of atherosclerosis.


Subject(s)
Apolipoprotein B-100/therapeutic use , Atherosclerosis/therapy , Dendritic Cells/transplantation , Hypercholesterolemia/therapy , Immunotherapy/methods , Animals , Aorta/immunology , Aorta/pathology , Atherosclerosis/immunology , CD4-Positive T-Lymphocytes/immunology , Chronic Disease , Dendritic Cells/immunology , Humans , Hypercholesterolemia/immunology , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Interleukin-10/therapeutic use , Lymphocyte Activation/immunology , Male , Mice , Spleen/immunology , Th1 Cells/immunology , Th2 Cells/immunology
17.
PLoS Pathog ; 6(2): e1000762, 2010 Feb 19.
Article in English | MEDLINE | ID: mdl-20174556

ABSTRACT

Hepatitis C virus (HCV), a major cause of chronic liver disease in humans, is the focus of intense research efforts worldwide. Yet structural data on the viral envelope glycoproteins E1 and E2 are scarce, in spite of their essential role in the viral life cycle. To obtain more information, we developed an efficient production system of recombinant E2 ectodomain (E2e), truncated immediately upstream its trans-membrane (TM) region, using Drosophila melanogaster cells. This system yields a majority of monomeric protein, which can be readily separated chromatographically from contaminating disulfide-linked aggregates. The isolated monomeric E2e reacts with a number of conformation-sensitive monoclonal antibodies, binds the soluble CD81 large external loop and efficiently inhibits infection of Huh7.5 cells by infectious HCV particles (HCVcc) in a dose-dependent manner, suggesting that it adopts a native conformation. These properties of E2e led us to experimentally determine the connectivity of its 9 disulfide bonds, which are strictly conserved across HCV genotypes. Furthermore, circular dichroism combined with infrared spectroscopy analyses revealed the secondary structure contents of E2e, indicating in particular about 28% beta-sheet, in agreement with the consensus secondary structure predictions. The disulfide connectivity pattern, together with data on the CD81 binding site and reported E2 deletion mutants, enabled the threading of the E2e polypeptide chain onto the structural template of class II fusion proteins of related flavi- and alphaviruses. The resulting model of the tertiary organization of E2 gives key information on the antigenicity determinants of the virus, maps the receptor binding site to the interface of domains I and III, and provides insight into the nature of a putative fusogenic conformational change.


Subject(s)
Antigens, Viral/chemistry , Viral Envelope Proteins/chemistry , Antigens, Viral/immunology , Cell Line , Circular Dichroism , Humans , Models, Molecular , Protein Structure, Tertiary , Recombinant Proteins , Spectroscopy, Fourier Transform Infrared , Viral Envelope Proteins/immunology
18.
BMC Ecol ; 12: 2, 2012 Feb 22.
Article in English | MEDLINE | ID: mdl-22356775

ABSTRACT

BACKGROUND: Most species of brown macroalgae recruit exclusively sexually. However, Fucus radicans, a dominant species in the northern Baltic Sea, recruits new attached thalli both sexually and asexually. The level of asexual recruitment varies among populations from complete sexual recruitment to almost (> 90%) monoclonal populations. If phenotypic traits have substantial inherited variation, low levels of sexual activity will decrease population variation in these traits, which may affect function and resilience of the species. We assessed the level of inherited variation in nine phenotypic traits by comparing variation within and among three monoclonal groups and one group of unique multilocus genotypes (MLGs) sampled in the wild. RESULTS: Of the nine phenotypic traits, recovery after freezing, recovery after desiccation, and phlorotannin content showed substantial inherited variation, that is, phenotypic variation in these traits were to a large extend genetically determined. In contrast, variation in six other phenotypic traits (growth rate, palatability to isopod grazers, thallus width, distance between dichotomies, water content after desiccation and photochemical yield under ambient conditions) did not show significant signals of genetic variation at the power of analyses used in the study. Averaged over all nine traits, phenotypic variation within monoclonal groups was only 68% of the variation within the group of different MLGs showing that genotype diversity does affect the overall level of phenotypic variation in this species. CONCLUSIONS: Our result indicates that, in general, phenotypic diversity in populations of Fucus radicans increases with increased multilocus genotype (MLG) diversity, but effects are specific for individual traits. In the light of Fucus radicans being a foundation species of the northern Baltic Sea, we propose that increased MLG diversity (leading to increased trait variation) will promote ecosystem function and resilience in areas where F. radicans is common, but this suggestion needs experimental support.


Subject(s)
Acclimatization/genetics , Fucus/cytology , Genetic Variation , Phenotype , Reproduction, Asexual/physiology , Tannins/genetics , Acclimatization/physiology , Analysis of Variance , Baltic States , Fluorescence , Fucus/genetics , Fucus/growth & development , Genotype , Microsatellite Repeats/genetics , Oceans and Seas , Reproduction/genetics , Reproduction/physiology , Reproduction, Asexual/genetics , Tannins/analysis
19.
Nat Commun ; 13(1): 6400, 2022 Oct 27.
Article in English | MEDLINE | ID: mdl-36302850

ABSTRACT

Shared cars will likely have larger annual vehicle driving distances than individually owned cars. This may accelerate passenger car retirement. Here we develop a semi-empirical lifetime-driving intensity model using statistics on Swedish vehicle retirement. This semi-empirical model is integrated with a carbon footprint model, which considers future decarbonization pathways. In this work, we show that the carbon footprint depends on the cumulative driving distance, which depends on both driving intensity and calendar aging. Higher driving intensities generally result in lower carbon footprints due to increased cumulative driving distance over the vehicle's lifetime. Shared cars could decrease the carbon footprint by about 41% in 2050, if one shared vehicle replaces ten individually owned vehicles. However, potential empty travel by autonomous shared vehicles-the additional distance traveled to pick up passengers-may cause carbon footprints to increase. Hence, vehicle durability and empty travel should be considered when designing low-carbon car sharing systems.

20.
Clim Change ; 172(1-2): 1, 2022.
Article in English | MEDLINE | ID: mdl-35529022

ABSTRACT

It has been claimed that COVID-19 public stimulus packages could be sufficient to meet the short-term energy investment needs to leverage a shift toward a pathway consistent with the 1.5 °C target of the Paris Agreement. Here, we provide complementary perspectives to reiterate that substantial, broad, and sustained policy efforts beyond stimulus packages will be needed for achieving the Paris Agreement long-term targets. Low-carbon investments will need to scale up and persist over the next several decades following short-term stimulus packages. The required total energy investments in the real world can be larger than the currently available estimates from integrated assessment models (IAMs). Existing databases from IAMs are not sufficient for analyzing the effect of public spending on emission reduction. To inform what role COVID-19 stimulus packages and public investments may play for reaching the Paris Agreement targets, explicit modelling of such policies is required.

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