| 1. |
- Pyykko, Okko T., et al.
(författare)
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Incidence, Comorbidities, and Mortality in Idiopathic Normal Pressure Hydrocephalus
- 2018
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Ingår i: World Neurosurgery. - : ELSEVIER SCIENCE INC. - 1878-8750 .- 1878-8769. ; 112, s. E624-E631
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Tidskriftsartikel (refereegranskat)abstract
- OBJECT: To investigate the incidence, comorbidities, mortality, and causes of death in idiopathic normal pressure hydrocephalus (iNPH). METHODS: A cohort of 536 patients with possible NPH from a defined population with a median follow-up time of 5.1 years, (range 0.04-19.9 years) was included in the study. Patients were evaluated by brain imaging and intraventricular pressure monitoring, with a brain biopsy specimen immunostained against amyloid-beta and hyper-phosphorylated tau. Hospital records were reviewed for vascular diseases and type 2 diabetes mellitus (T2DM). Death certificates and yearly population of the catchment area were obtained from national registries. RESULTS: A total of 283 patients had a clinical diagnosis of iNPH, leading to a median annual incidence of 1.58 iNPH patients per 100,000 inhabitants (range, 0.8-4.5). Alzeimer disease-related brain biopsy findings were less frequent in iNPH patients than in non-iNPH patients (P < 0.05). An overrepresentation of hypertension (52% vs. 33%, P < 0.001) and T2DM (23% vs. 13%, P = 0.002) was noted in iNPH patients. Age (hazard ratio [HR] 1.04/year, 95% confidence interval [CI] 1.03-1.06, P< 0.001) and T2DM (HR 1.63, 95% CI 1.23-2.16, P < 0.001) increased the risk of death in the iNPH patients and in the total population. iNPH was associated with decreased risk of death (HR 0.63, 95% CI 0.50-0.78, P < 0.001). The most frequent causes of death were cardiovascular and cerebrovascular disease. Dementia as a cause of death was more common in non-iNPH patients (27% vs. 10%, P < 0.001). CONCLUSIONS: Hypertension and T2DM are common in iNPH and the latter causes excess mortality in the affected patients.
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| 2. |
- Rollauer, Sarah E., et al.
(författare)
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Structure of the TatC core of the twin-arginine protein transport system
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7428, s. 210-
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Tidskriftsartikel (refereegranskat)abstract
- The twin-arginine translocation (Tat) pathway is one of two general protein transport systems found in the prokaryotic cytoplasmic membrane and is conserved in the thylakoid membrane of plant chloroplasts. The defining, and highly unusual, property of the Tat pathway is that it transports folded proteins, a task that must be achieved without allowing appreciable ion leakage across the membrane. The integral membrane TatC protein is the central component of the Tat pathway. TatC captures substrate proteins by binding their signal peptides. TatC then recruits TatA family proteins to form the active translocation complex. Here we report the crystal structure of TatC from the hyperthermophilic bacterium Aquifex aeolicus. This structure provides a molecular description of the core of the Tat translocation system and a framework for understanding the unique Tat transport mechanism.
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| 3. |
- Tarry, Michael, et al.
(författare)
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The Extra-Membranous Domains of the Competence Protein HofQ Show DNA Binding, Flexibility and a Shared Fold with Type I KH Domains
- 2011
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 409:4, s. 642-653
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Tidskriftsartikel (refereegranskat)abstract
- Secretins form large oligomeric assemblies in the membrane that control both macromolecular secretion and uptake. Several Pasteurellaceae are naturally competent for transformation, but the mechanism for DNA assimilation is largely unknown. In Haemophilus influenzae, the secretin ComE has been demonstrated to be essential for DNA uptake. In closely related Aggregatibacter actinomycetemcomitans, an opportunistic pathogen in periodontitis, the ComE homolog HofQ is believed to be the outer membrane DNA translocase. Here, we report the structure of the extramembranous domains of HofQ at 2.3 angstrom resolution by X-ray crystallography. We also show that the extra-membranous domains of HofQ are capable of DNA binding. The structure reveals two secretin-like folds, the first of which is formed by means of a domain swap. The second domain displays extensive structural similarity to K homology (KH) domains, including the presence of a GxxG motif, which is essential for the nucleotide-binding function of KH domains, suggesting a possible mechanism for DNA binding by HofQ. The data indicate a direct involvement in DNA acquisition and provide insight into the molecular basis for natural competence.
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