732 research outputs found

    Insights into mitochondrial dysfunction: aging, amyloid-β, and tau-A deleterious trio

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    Significance: Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder mainly affecting elderly individuals. The pathology of AD is characterized by amyloid plaques (aggregates of amyloid-β [Aβ]) and neurofibrillary tangles (aggregates of tau), but the mechanisms underlying this dysfunction are still partially unclear. Recent Advances: A growing body of evidence supports mitochondrial dysfunction as a prominent and early, chronic oxidative stress-associated event that contributes to synaptic abnormalities and, ultimately, selective neuronal degeneration in AD. Critical Issues: In this review, we discuss on the one hand whether mitochondrial decline observed in brain aging is a determinant event in the onset of AD and on the other hand the close interrelationship of this organelle with Aβ and tau in the pathogenic process underlying AD. Moreover, we summarize evidence from aging and Alzheimer models showing that the harmful trio "aging, Aβ, and tau protein" triggers mitochondrial dysfunction through a number of pathways, such as impairment of oxidative phosphorylation (OXPHOS), elevation of reactive oxygen species production, and interaction with mitochondrial proteins, contributing to the development and progression of the disease. Future Directions: The aging process may weaken the mitochondrial OXPHOS system in a more general way over many years providing a basis for the specific and destructive effects of Aβ and tau. Establishing strategies involving efforts to protect cells at the mitochondrial level by stabilizing or restoring mitochondrial function and energy homeostasis appears to be challenging, but very promising route on the horizon

    Pregnancy Outcome in Women With APECED (APS-1) : A Multicenter Study on 43 Females With 83 Pregnancies

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    Context: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED; also known as autoimmune polyendocrine syndrome type 1) has a severe, unpredictable course. Autoimmunity and disease components may affect fertility and predispose to maternal and fetal complications, but pregnancy outcomes remain unknown. Objective: To assess fetal and maternal outcomes and course of clinical APECED manifestations during pregnancy in women with APECED. Design and Setting: A multicenter registry-based study including 5 national patient cohorts. Patients: 321 females with APECED. Main Outcome Measure: Number of pregnancies, miscarriages, and deliveries. Results: Forty-three patients had altogether 83 pregnancies at median age of 27 years (range, 17-39). Sixty (72%) pregnancies led to a delivery, including 2 stillbirths (2.4%) and 5 (6.0%) preterm livebirths. Miscarriages, induced abortions, and ectopic pregnancies were observed in 14 (17%), 8 (10%), and 1 (1.2%) pregnancies, respectively. Ovum donation resulted in 5 (6.0%) pregnancies. High maternal age, premature ovarian insufficiency, primary adrenal insufficiency, or hypoparathyroidism did not associate with miscarriages. Women with livebirth had, on average, 4 APECED manifestations (range 0-10); 78% had hypoparathyroidism, and 36% had primary adrenal insufficiency. APECED manifestations remained mostly stable during pregnancy, but in 1 case, development of primary adrenal insufficiency led to adrenal crisis and stillbirth. Birth weights were normal in >80% and apart from 1 neonatal death of a preterm baby, no serious perinatal complications occurred. Conclusions. Outcome of pregnancy in women with APECED was generally favorable. However, APECED warrants careful maternal multidisciplinary follow-up from preconceptual care until puerperium.Peer reviewe

    Cruise Report Poseidon 229a/b Kolbeinsey Ridge, Akureyri - Reykjavik, 22.05.1997 - 11.06.1997

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    General Subject of research: Detailed study of the shallow water hydrothermal system around Kolbeinsey and Grimsey island

    Processes associated with ionic current rectification at a 2D-titanate nanosheet deposit on a microhole poly(ethylene terephthalate) substrate

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    Films of titanate nanosheets (approx. 1.8-nm layer thickness and 200-nm size) having a lamellar structure can form electrolyte-filled semi-permeable channels containing tetrabutylammonium cations. By evaporation of a colloidal solution, persistent deposits are readily formed with approx. 10-μm thickness on a 6-μm-thick poly(ethylene-terephthalate) (PET) substrate with a 20-μm diameter microhole. When immersed in aqueous solution, the titanate nanosheets exhibit a p.z.c. of − 37 mV, consistent with the formation of a cation conducting (semi-permeable) deposit. With a sufficiently low ionic strength in the aqueous electrolyte, ionic current rectification is observed (cationic diode behaviour). Currents can be dissected into (i) electrolyte cation transport, (ii) electrolyte anion transport and (iii) water heterolysis causing additional proton transport. For all types of electrolyte cations, a water heterolysis mechanism is observed. For Ca 2+ and Mg 2+ ions, water heterolysis causes ion current blocking, presumably due to localised hydroxide-induced precipitation processes. Aqueous NBu 4 + is shown to ‘invert’ the diode effect (from cationic to anionic diode). Potential for applications in desalination and/or ion sensing are discussed. [Figure not available: see fulltext.]. </p

    Microstructural, thermal, crystallization, and water absorption properties of films prepared from never-dried and freeze-dried cellulose nanocrystals

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    In this paper, the microstructural, optical, thermal, crystallization, and water absorption properties of films prepared from never-dried (ND) and freeze-dried (FD) cellulose nanocrystals (CNCs) are reported. Morphology of the ND CNCs reveals a needle-like structure, while after freeze-drying, they show a flake-like morphology. Microstructural analysis of ND and FD CNCs are further studied via small angle X-ray scattering to probe interactions. ND CNCs yield a transparent film with a low surface roughness (14 ± 4 nm), while the FD CNC film evidence a significant reduction of their transparency due to their higher surface roughness (134 ± 20 nm). Although Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy analyses reveal no chemical change occurs during the freeze-drying process, yet a more intense thermal degradation profile is observed for FD CNC film, probably due to the higher oxygen ingress within the gaps created between the stacked flakes. This, in turn, results in a greater loss of crystallinity at a higher temperature (300 °C) compared to the ND CNC film. A rapid decrease in water contact angle of the FD CNC film proves that the morphology of flakes and their orientation within the film has a strong influence in increasing water absorption capacity
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