Altered proteostasis is a salient feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress and abnormal protein aggregation. ER stress triggers the activation of the unfolded protein response (UPR), a signaling pathway that enforces adaptive programs to sustain proteostasis or eliminate terminally damaged cells. IRE1 is an ER-located kinase and endoribonuclease that operates as a major stress transducer, mediating both adaptive and proapoptotic programs under ER stress. IRE1 signaling controls the expression of the transcription factor XBP1, in addition to degrade several RNAs. Importantly, a polymorphism in the XBP1 promoter was suggested as a risk factor to develop AD. Here, we demonstrate a positive correlation between the progression of AD histopathology and the activation of IRE1 in human brain tissue. To define the significance of the UPR to AD, we targeted IRE1 expression in a transgenic mouse model of AD. Despite initial expectations that IRE1 signaling may protect against AD, genetic ablation of the RNase domain of IRE1 in the nervous system significantly reduced amyloid deposition, the content of amyloid β oligomers, and astrocyte activation. IRE1 deficiency fully restored the learning and memory capacity of AD mice, associated with improved synaptic function and improved long-term potentiation (LTP). At the molecular level, IRE1 deletion reduced the expression of amyloid precursor protein (APP) in cortical and hippocampal areas of AD mice. In vitro experiments demonstrated that inhibition of IRE1 downstream signaling reduces APP steady-state levels, associated with its retention at the ER followed by proteasome-mediated degradation. Our findings uncovered an unanticipated role of IRE1 in the pathogenesis of AD, offering a novel target for disease intervention.
To evaluate the potential use of mesquite (Prosopis chilensis (Mol) Stuntz) seed gum, the behaviour of the gum was studied using two extraction methods (alkaline and acid), different pH values, two concentrations (0.2 and 0.4% w/v) and different temperatures. The capacity of the gum to stabilise food foams was also evaluated. The alkaline extraction yield (24.9%) was higher than the acid extraction yield (17.7%). Owing molecular to hydrolysis caused by the acid, acid extraction resulted in a lower protein content. Gum from acid extraction had a higher viscosity than that from alkaline extraction at all temperatures investigated (10, 20, 30, 40, 50 and 60 • C). There were no significant differences between the viscosities of mucilage dispersions at the different values of pH studied (3.0, 4.0 and 5.0). The addition of extracted mesquite gum (obtained by either method and at either concentration studied) to egg white foam provided a higher stability and decreased the liquid drainage and collapse of the foam.
Aim of study: The aim of the study was to assess the effect of water availability on plastic responses and biomass allocation in early growth traits of Pinus radiata D. Don.Area of study: Seedlings of 69 families of P. radiata belonging to five different sites in Central Chile, ranging from coastal range to fothills of the Andes, were grown in controlled conditions to evaluate differences in response to watering.Material and methods: The seedlings were subjected to two watering regimes: well-watered treatment, in which seedlings were watered daily, and water stress treatment in which seedlings were subjected to three cyclic water deficits by watering to container capacity on 12 days cycles each. After twenty-eight weeks root collar diameter, height, shoot dry weight (stem + needles), root dry weight, total dry weight, height/diameter ratio and root/shoot ratio were recorded. Patterns and amounts of phenotypic changes, including changes in biomass allocation, were analyzed.Main results: Families from coastal sites presented high divergence for phenotypic changes, allocating more biomass to shoots, and those families from interior sites presented low phenotypic plasticity, allocating more biomass to roots at the expense of shoots. These changes are interpreted as a plastic response and leads to the conclusion that the local landrace of P. radiata in Chile originating from contrasting environments possess distinct morphological responses to water deficit which in turn leads to phenotypic plasticity.Research highlights: Families belonging to sandy soil sites must be considered for tree breeding in dry areas, selecting those with high root: shoot ratio.Key words: early testing; environmental interaction; ontogeny; plasticity index; water stress.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.