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Göteborg, Sweden

Johnsson M.,Linkoping University | Gustafson I.,Linkoping University | Rubin C.-J.,Uppsala University | Sahlqvist A.-S.,Uppsala University | And 7 more authors.
PLoS Genetics | Year: 2012

Domestication is one of the strongest forms of short-term, directional selection. Although selection is typically only exerted on one or a few target traits, domestication can lead to numerous changes in many seemingly unrelated phenotypes. It is unknown whether such correlated responses are due to pleiotropy or linkage between separate genetic architectures. Using three separate intercrosses between wild and domestic chickens, a locus affecting comb mass (a sexual ornament in the chicken) and several fitness traits (primarily medullary bone allocation and fecundity) was identified. This locus contains two tightly-linked genes, BMP2 and HAO1, which together produce the range of pleiotropic effects seen. This study demonstrates the importance of pleiotropy (or extremely close linkage) in domestication. The nature of this pleiotropy also provides insights into how this sexual ornament could be maintained in wild populations. © 2012 Johnsson et al.

Hansson E.,The Sahlgrenska Academy
Scandinavian Journal of Pain | Year: 2010

Nociceptive and neuropathic pain signals are known to result from noxious stimuli, which are converted into electrical impulses within tissue nociceptors. There is a complex equilibrium of pain-signalling and pain-relieving pathways connecting PNS and CNS. Drugs against long-term pain are today directed against increased neuronal excitability, mostly with less success. An injury often starts with acute physiological pain, which becomes inflammatory, nociceptive, or neuropathic, and may be transferred into long-term pain. Recently a low-grade inflammation was identified in the spinal cord and along the pain pathways to thalamus and the parietal cortex. This neuroinflammation is due to activation of glial cells, especially microglia, with production of cytokines and other inflammatory mediators within the CNS. Additionally, substances released to the blood from the injured region influence the blood-brain barrier, and give rise to an increased permeability of the tight junctions of the capillary endothelial cells, leading to passage of blood cells into the CNS. These cells are transformed into reactive microglia. If the inflammation turns into a pathological state the astrocytes will be activated. They are coupled into networks and respond to substances released by the capillary endothelial cells, to cytokines released from microglia, and to neurotransmitters and peptides released from neurons. As the astrocytes occupy a strategic position between the vasculature and synapses, they monitor the neuronal activity and transmitter release. Increased release of glutamate and ATP leads to disturbances in Ca2+ signalling, increased production of cytokines and free radicals, attenuation of the astrocyte glutamate transport capacity, and conformational changes in the astrocytic cytoskeleton, the actin filaments, which can lead to formation and rebuilding of new synapses. New neuronal contacts are established for maintaining and spreading pain sensation with the astrocytic networks as bridges. Thereby the glial cells can maintain the pain sensation even after the original injury has healed, and convert the pain into long-term by altering neuronal excitability. It can even be experienced from other parts of the body. As astrocytes are intimate co-players with neurons in the CNS, more knowledge on astrocyte responses to inflammatory activators may give new insight in our understanding of mechanisms of low-grade inflammation underlying long-term pain states and pain spreading. Novel treatment strategies would be to restore glial cell function and thereby attenuate the neuroinflammation. © 2010 Scandinavian Association for the Study of Pain.

Bergman O.,Gothenburg University | Hakansson A.,Gothenburg University | Westberg L.,Gothenburg University | Nordenstrom K.,Gothenburg University | And 6 more authors.
Neurobiology of Aging | Year: 2010

PITX3 is a transcription factor of importance for the differentiation and survival of midbrain dopaminergic neurons, the gene of which is disrupted in a putative mouse model for Parkinson's disease (PD). The A-allele of a HapMap tagging SNP (rs4919621) that was genotyped in a population of 361 PD patients, 69 of which had early onset, and in 333 controls, was significantly more common in PD patients with an early age of onset when compared either to controls (p = 0.002) or to PD patients with late onset (p = 0.001). In contrast, a previous finding suggesting a SNP (rs3758549) in the putative promoter region of the PITX3 gene to be associated with PD could not be replicated. © 2008 Elsevier Inc. All rights reserved.

Tobias J.,The Sahlgrenska Academy | Moerman L.,Ministry of Health | Bassal R.,The Israel Center for Disease Control | Green M.,The Israel Center for Disease Control | Green M.,Haifa University
Vaccine | Year: 2010

This study was undertaken to estimate the magnitude of Bordetella pertussis infections in a highly vaccinated population in Israel in order to evaluate the relationship between clinical notification data and serology-based evidence of infection. A cross-sectional survey was conducted on a total of 1982 serum samples from the National Serum Bank, collected from January 2000 through December 2001, in order to monitor high levels of pertussis toxin (PT) IgG antibody indicative of recent B. pertussis infection, by standardized methods. The estimation yielded an infection incidence rate of 2448 per 100,000 population (≥3 years of age) for the year 2000 compared to an annual incidence of reported pertussis of 5.6 per 100,000 for the same period. The peaks of estimated incidence of infection were found in the groups of 15-19-year olds (5245 per 100,000) and older than 60 years (6469 per 100,000), whereas the majority of clinical pertussis cases were reported for the 10-14-year olds (20.5 per 100,000). The findings clearly show that despite a high vaccination coverage rate (>93%), there is still a considerable circulation of B. pertussis, particularly in adolescents and elderly. Population-based serosurveillance for pertussis offers the potential to assist interpretation of trends independent of notification and diagnostic bias. © 2010 Elsevier Ltd. All rights reserved.

Harandi A.M.,The Sahlgrenska Academy | Medaglini D.,University of Siena | Shattock R.J.,St Georges, University of London
Vaccine | Year: 2010

The workshop on vaccine adjuvants was held in July of 2009 at the European Commission in Brussels, with the goal of identifying key scientific priorities as they pertain to the development of effective vaccines against life-threatening diseases especially those associated with poverty, including HIV/AIDS, malaria and tuberculosis as well as neglected infectious diseases. On the basis of new advances in adjuvant research and related technology as well as potential challenges and roadblocks, six priorities were identified to accelerate development of improved or novel vaccine adjuvants for human use.

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