Stockholm University

About: Stockholm University is a education organization based out in Stockholm, Sweden. It is known for research contribution in the topics: Population & Supernova. The organization has 21052 authors who have published 62567 publications receiving 2725859 citations. The organization is also known as: University of Stockholm & Stockholms universitet.

PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination.

Abstract: If replication forks are perturbed, a multifaceted response including several DNA repair and cell cycle checkpoint pathways is activated to ensure faithful DNA replication. Here, we show that poly(ADP-ribose) polymerase 1 (PARP1) binds to and is activated by stalled replication forks that contain small gaps. PARP1 collaborates with Mre11 to promote replication fork restart after release from replication blocks, most likely by recruiting Mre11 to the replication fork to promote resection of DNA. Both PARP1 and PARP2 are required for hydroxyurea-induced homologous recombination to promote cell survival after replication blocks. Together, our data suggest that PARP1 and PARP2 detect disrupted replication forks and attract Mre11 for end processing that is required for subsequent recombination repair and restart of replication forks.

Tumour and normal tissue responses to fractionated non-uniform dose delivery.

Abstract: The dose–volume response of tumours and normal tissues is discussed in terms of ‘parallelity’ and ‘seriality’. The volume dependence of the radiation response of a tumour depends primarily on the eradication of all its clonogenic cells and the tumour has a parallel organization. The response of heterogeneous tumours is examined, and it is shown that a small resistant clonogen population may cause a low dose–response gradient, γ. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of stem cells or differentiated cells that in addition may have a complex structural and functional organization. The volume dependence of the dose–response relation of normal tissues is therefore described here by a new parameter, the ‘relative seriality’, s, of the infrastructure of the organ. The model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose–response relat...

Biomimetic assembly and activation of [FeFe]-hydrogenases

Abstract: Hydrogenases are the most active molecular catalysts for hydrogen production and uptake1, 2, and could therefore facilitate the development of new types of fuel cell3, 4, 5. In [FeFe]-hydrogenases, catalysis takes place at a unique di-iron centre (the [2Fe] subsite), which contains a bridging dithiolate ligand, three CO ligands and two CN- ligands6, 7. Through a complex multienzymatic biosynthetic process, this [2Fe] subsite is first assembled on a maturation enzyme, HydF, and then delivered to the apo-hydrogenase for activation8. Synthetic chemistry has been used to prepare remarkably similar mimics of that subsite1, but it has failed to reproduce the natural enzymatic activities thus far. Here we show that three synthetic mimics (containing different bridging dithiolate ligands) can be loaded onto bacterial Thermotoga maritima HydF and then transferred to apo-HydA1, one of the hydrogenases of Chlamydomonas reinhardtii algae. Full activation of HydA1 was achieved only when using the HydF hybrid protein containing the mimic with an azadithiolate bridge, confirming the presence of this ligand in the active site of native [FeFe]-hydrogenases9, 10. This is an example of controlled metalloenzyme activation using the combination of a specific protein scaffold and active-site synthetic analogues. This simple methodology provides both new mechanistic and structural insight into hydrogenase maturation and a unique tool for producing recombinant wild-type and variant [FeFe]-hydrogenases, with no requirement for the complete maturation machinery

The betula prospective cohort study: Memory, health, and aging

Abstract: The objective of this article is to present an overview of a prospective cohort study involving a total of 3,000 subjects whose ages were 35, 40, 45, 50, 55, 60, 65, 70, 75, and 80 years when first tested. the design of the study includes three waves of data collection. the first of these waves was conducted in 1988-1990, the second in 1993-1995, and the third will be conducted in 1998-2000. One sample of 1,000 subjects in these age cohorts underwent testing in 1988-1990 (100 subjects per cohort). This sample and two additional samples were tested in 1993-1995 and will be tested again in 1998-2000. Subjects take part in extensive health and memory examinations, and interviews about social factors. the memory testing covers a wide range of memory functions. the chief objectives of the study are to (a) examine the development of health and memory in adulthood and old age; (b) determine early preclinical signs of dementia; (c) determine risk factors for dementia; and (d) assess premorbid memory func...