| 1. |
- Cardwell, C R, et al.
(författare)
-
Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data
- 2010
-
Ingår i: DIABETOLOGIA. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 53:4, s. 641-651
-
Tidskriftsartikel (refereegranskat)abstract
- We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p = 0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p = 0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p = 0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.
|
|
| 2. |
|
|
| 3. |
- Sommer, Martha E., et al.
(författare)
-
The European Research Network on Signal Transduction (ERNEST) : Toward a Multidimensional Holistic Understanding of G Protein-Coupled Receptor Signaling
- 2020
-
Ingår i: ACS Pharmacology & Translational Science. - : American Chemical Society (ACS). - 2575-9108. ; 3:2, s. 361-370
-
Tidskriftsartikel (refereegranskat)abstract
- G protein-coupled receptors (GPCRs) are intensively studied due to their therapeutic potential as drug targets. Members of this large family of transmembrane receptor proteins mediate signal transduction in diverse cell types and play key roles in human physiology and health. In 2013 the research consortium GLISTEN (COST Action CM1207) was founded with the goal of harnessing the substantial growth in knowledge of GPCR structure and dynamics to push forward the development of molecular modulators of GPCR function. The success of GLISTEN, coupled with new findings and paradigm shifts in the field, led in 2019 to the creation of a related consortium called ERNEST (COST Action CA18133). ERNEST broadens focus to entire signaling cascades, based on emerging ideas of how complexity and specificity in signal transduction are not determined by receptor-ligand interactions alone. A holistic approach that unites the diverse data and perspectives of the research community into a single multidimensional map holds great promise for improved drug design and therapeutic targeting.
|
|
| 4. |
- Bartlett, S E, et al.
(författare)
-
Dopamine responsiveness is regulated by targeted sorting of D2 receptors
- 2005
-
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 102:32, s. 11521-11526
-
Tidskriftsartikel (refereegranskat)abstract
- Aberrant dopaminergic signaling is a critical determinant in multiple psychiatric disorders, and in many disease states, dopamine receptor number is altered. Here we identify a molecular mechanism that selectively targets D2 receptors for degradation after their activation by dopamine. The degradative fate of D2 receptors is determined by an interaction with G protein coupled receptor-associated sorting protein (GASP). As a consequence of this GASP interaction, D2 responses in rat brain fail to resensitize after agonist treatment. Disruption of the D2-GASP interaction facilitates recovery of D2 responses, suggesting that modulation of the D2-GASP interaction is important for the functional down-regulation of D2 receptors.
|
|
| 5. |
|
|
