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| 2. |
- Baldock, Paul A., et al.
(författare)
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Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis
- 2007
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Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 282:26, s. 19092-19102
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Tidskriftsartikel (refereegranskat)abstract
- The importance of neuropeptide Y (NPY) and Y2 receptors in the regulation of bone and energy homeostasis has recently been demonstrated. However, the contributions of the other Y receptors are less clear. Here we show that Y1 receptors are expressed on osteoblastic cells. Moreover, bone and adipose tissue mass are elevated in Y1(-/-) mice with a generalized increase in bone formation on cortical and cancellous surfaces. Importantly, the inhibitory effects of NPY on bone marrow stromal cells in vitro are absent in cells derived from Y1(-/-) mice, indicating a direct action of NPY on bone cells via this Y receptor. Interestingly, in contrast to Y2 receptor or germ line Y1 receptor deletion, conditional deletion of hypothalamic Y1 receptors in adult mice did not alter bone homeostasis, food intake, or adiposity. Furthermore, deletion of both Y1 and Y2 receptors did not produce additive effects in bone or adiposity. Thus Y1 receptor pathways act powerfully to inhibit bone production and adiposity by nonhypothalamic pathways, with potentially direct effects on bone tissue through a single pathway with Y2 receptors.
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| 4. |
- Lai, I. H, et al.
(författare)
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A unique tetrameric structure of deer plasma haptoglobin – an evolutionary advantage in the Hp 2-2 phenotype with homogeneous structure
- 2008
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Ingår i: FEBS Journal. - 1742-4658 .- 1742-464X. ; 275, s. 981-993
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Tidskriftsartikel (refereegranskat)abstract
- Similar to blood types, human plasma haptoglobin (Hp) is classified intothree phenotypes: Hp 1-1, 2-1 and 2-2. They are genetically inheritedfrom two alleles Hp 1 and Hp 2 (represented in bold), but only theHp 1-1 phenotype is found in almost all animal species. The Hp 2-2protein consists of complicated large polymers cross-linked by a2-bsubunits or (a2-b)n (where n ‡ 3, up to 12 or more), and is associatedwith the risk of the development of diabetic, cardiovascular and inflammatorydiseases. In the present study, we found that deer plasma Hpmimics human Hp 2, containing a tandem repeat over the a-chain basedon our cloned cDNA sequence. Interestingly, the isolated deer Hp ishomogeneous and tetrameric, i.e. (a-b)4, although the locations of )SHgroups (responsible for the formation of polymers) are exactly identicalto that of human. Denaturation of deer Hp using 6 m urea under reducingconditions (143 mm b-mercaptoethanol), followed by renaturation,sustained the formation of (a-b)4, suggesting that the Hp tetramers arenot randomly assembled. Interestingly, an a-chain monoclonal antibody(W1), known to recognize both human and deer a-chains, only binds tointact human Hp polymers, but not to deer Hp tetramers. This impliesthat the epitope of the deer a-chain is no longer exposed on the surfacewhen Hp tetramers are formed. We propose that steric hindrance playsa major role in determining the polymeric formation in human and deerpolymers. Phylogenetic and immunochemical analyses revealed that theHp 2 allele of deer might have arisen at least 25 million years ago. Amechanism involved in forming Hp tetramers is proposed and discussed,and the possibility is raised that the evolved tetrameric structure of deerHp might confer a physiological advantage.
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| 6. |
- Lundervold, Astri. J., et al.
(författare)
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Intellectual function in children with teacher reported language problems.
- 2008
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 49:2, s. 187-193
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Tidskriftsartikel (refereegranskat)abstract
- We predicted that teacher reported language problems are associated with low IQ, even when gender and behavior-emotional disorders are controlled for. All subjects were participants in a population based study. In stage 1, teachers completed a questionnaire containing four items pertaining to language function. A case-control sample (n= 294) was assessed using WISC-III and Kiddie-SADS-PL. A child was defined with "language problems" (LP) if s/he obtained a score indicating severe problems on at least one item. Teacher reported LP was found in 9.9% of the population sample and 20.7% of the case-control sample, with a three-fold higher risk for boys than girls. The LP group obtained significantly lower scores on all WISC-III factors compared with the non-LP group. The differences were not accounted for by the presence of behavioral-emotional disorders. When primary school teachers report LP, further assessment of the child's cognitive function is warranted.
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| 7. |
- Toft Sörensen, Andreas, et al.
(författare)
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Activity-dependent volume transmission by transgene NPY attenuates glutamate release and LTP in subiculum
- 2008
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Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431. ; 39:2, s. 37-229
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptide Y (NPY) gene transduction of the brain using viral vectors in epileptogenic regions can effectively suppress seizures in animals, and is being considered as a promising alternative treatment strategy for epilepsy. Therefore, it is fundamental to understand the detailed mechanisms governing the release and action of transgene NPY in neuronal circuitries. Using whole-cell recordings from subicular neurons, we show that in animals transduced by recombinant adeno-associated viral (rAAV) vector carrying the NPY gene, transgene NPY is released during high-frequency activation of CA1-subicular synapses. Released transgene NPY attenuates excitatory synaptic transmission not only in activated, but also in neighboring, non-activated synapses. Such broad action of transgene NPY may prevent recruitment of excitatory synapses in epileptic activity and could play a key role in limiting the spread and generalization of seizures.
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| 8. |
- Toft Sörensen, Andreas, et al.
(författare)
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Hippocampal NPY gene transfer attenuates seizures without affecting epilepsy-induced impairment of LTP.
- 2009
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 215, s. 328-333
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Tidskriftsartikel (refereegranskat)abstract
- Recently, hippocampal neuropeptide Y (NPY) gene therapy has been shown to effectively suppress both acute and chronic seizures in animal model of epilepsy, thus representing a promising novel antiepileptic treatment strategy, particularly for patients with intractable mesial temporal lobe epilepsy (TLE). However, our previous studies show that recombinant adeno-associated viral (rAAV)-NPY treatment in naive rats attenuates long-term potentiation (LTP) and transiently impairs hippocampal learning process, indicating that negative effect on memory function could be a potential side effect of NPY gene therapy. Here we report how rAAV vector-mediated overexpression of NPY in the hippocampus affects rapid kindling, and subsequently explore how synaptic plasticity and transmission is affected by kindling and NPY overexpression by field recordings in CA1 stratum radiatum of brain slices. In animals injected with rAAV-NPY, we show that rapid kindling-induced hippocampal seizures in vivo are effectively suppressed as compared to rAAV-empty injected (control) rats. Six to nine weeks later, basal synaptic transmission and short-term synaptic plasticity are unchanged after rapid kindling, while LTP is significantly attenuated in vitro. Importantly, transgene NPY overexpression has no effect on short-term synaptic plasticity, and does not further compromise LTP in kindled animals. These data suggest that epileptic seizure-induced impairment of memory function in the hippocampus may not be further affected by rAAV-NPY treatment, and may be considered less critical for clinical application in epilepsy patients already experiencing memory disturbances.
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| 9. |
- Wu, Xifeng, et al.
(författare)
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Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer.
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:9, s. 991-5
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations. Combining all subjects (6,667 cases, 39,590 controls), the overall P-value was 2.14 x 10(-10) and the allelic odds ratio was 1.15 (95% confidence interval 1.10-1.20). rs2294008 alters the start codon and is predicted to cause truncation of nine amino acids from the N-terminal signal sequence of the primary PSCA translation product. In vitro reporter gene assay showed that the variant allele significantly reduced promoter activity. Resequencing of the PSCA genomic region showed that rs2294008 is the only common missense SNP in PSCA. Our data identify rs2294008 as a new bladder cancer susceptibility locus.
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