Sosa A.L.,National Autonomous University of Mexico |
Albanese E.,U.S. National Institute on Aging |
Stephan B.C.M.,University of Cambridge |
Dewey M.,Kings College London |
And 15 more authors.
PLoS Medicine | Year: 2012
Background: Rapid demographic ageing is a growing public health issue in many low- and middle-income countries (LAMICs). Mild cognitive impairment (MCI) is a construct frequently used to define groups of people who may be at risk of developing dementia, crucial for targeting preventative interventions. However, little is known about the prevalence or impact of MCI in LAMIC settings. Methods and Findings: Data were analysed from cross-sectional surveys established by the 10/66 Dementia Research Group and carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India on 15,376 individuals aged 65+ without dementia. Standardised assessments of mental and physical health, and cognitive function were carried out including informant interviews. An algorithm was developed to define Mayo Clinic amnestic MCI (aMCI). Disability (12-item World Health Organization disability assessment schedule [WHODAS]) and informant-reported neuropsychiatric symptoms (neuropsychiatric inventory [NPI-Q]) were measured. After adjustment, aMCI was associated with disability, anxiety, apathy, and irritability (but not depression); between-country heterogeneity in these associations was only significant for disability. The crude prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Country differences changed little (range 0.6%-4.6%) after standardization for age, gender, and education level. In pooled estimates, aMCI was modestly associated with male gender and fewer assets but was not associated with age or education. There was no significant between-country variation in these demographic associations. Conclusions: An algorithm-derived diagnosis of aMCI showed few sociodemographic associations but was consistently associated with higher disability and neuropsychiatric symptoms in addition to showing substantial variation in prevalence across LAMIC populations. Longitudinal data are needed to confirm findings-in particular, to investigate the predictive validity of aMCI in these settings and risk/protective factors for progression to dementia; however, the large number affected has important implications in these rapidly ageing settings. Please see later in the article for the Editors' Summary. © 2012 Sosa et al. Source
Makarov V.,UPR |
Kucheryavykh L.,UCC |
Kucheryavykh Y.,UCC |
Rivera A.,UCC |
And 3 more authors.
Journal of Biophysics | Year: 2013
It is known that secondary transporters, which utilize transmembrane ionic gradients to drive their substrates up a concentration gradient, can reverse the uptake and instead release their substrates. Unfortunately, the Michaelis-Menten kinetic scheme, which is popular in transporter studies, does not include transporter reversal, and it completely neglects the possibility of equilibrium between the substrate concentrations on both sides of the membrane. We have developed a complex two-substrate kinetic model that includes transport reversal. This model allows us to construct analytical formulas allowing the calculation of a "heteroexchange" and "transacceleration" using standard Michaelis coefficients for respective substrates. This approach can help to understand how glial and other cells accumulate substrates without synthesis and are able to release such substrates and gliotransmitters. © 2013 V. Makarov et al. Source
The ability of mammalian cells to recognize and respond to pathogenic invaders at the earliest stages of infection is crucial for immunity. Many host-cell receptors have been identified that recognize evolutionarily conserved microbial components, such as cell-wall peptidoglycan, to rapidly activate the innate immune system1. In this issue, Keestra-Gounder et al.2 (page 394) describe a curious connection whereby stress in the endoplasmic reticulum (ER), a membrane-bound compartment responsible for the synthesis of secreted cytokine proteins, triggers a cytoplasmic 'danger' signal leading to the release of inflammatory proteins that activate an innate immune response. Even more surprisingly, this ER stress signal is transduced through NOD1 and NOD2 — sensors that respond to fragments of bacterial peptidoglycans — yet takes place in the absence of these molecules. A wide variety of pathogens hijack and/or manipulate the ER of host cells3. Such infection often activates the stress-responsive control system of this organelle, termed the unfolded protein response (UPR)4, 5. Previous work indicates that activation of IRE1α, a transmembrane kinase enzyme required for the UPR, leads to inflammation, although the mechanisms involved remain unclear6, 7. To avoid triggering the immune response, several bacterial pathogens actively inhibit the UPR3. By contrast, Brucella abortus, a bacterial pathogen that causes septic abortion in livestock, and which occasionally infects humans through contaminated dairy products, actively promotes UPR-induced inflammation through its secreted effector protein VceC (ref. 8). Keestra-Gounder et al. demonstrate that blocking either ER stress or the activity of the stress sensor IRE1α during infection with B. abortus in mice markedly lowered production of the cytokine IL-6 and other mediators of inflammation. Conversely, triggering the UPR in mouse macrophage cells, either with chemical inducers or by expressing the B. abortus VceC protein, resulted in IL-6 release. However, a major twist came when the researchers investigated the mechanism by which the UPR triggered IL-6 release and identified the requirement for NOD1 and NOD2. Keestra-Gounder and colleagues found that genetic inactivation of both receptors, or deletion of the downstream enzyme RIP2, greatly reduced cytokine signalling in response to ER stress. Importantly, these sensors were activated in the absence of bacterial ligands, implying that NOD receptors can participate in both bacterial-ligand-dependent and -independent inflammatory responses (Fig. 1). The authors then investigated UPR-mediated inflammation in B. abortus infection in vivo. When they treated pregnant mice infected with B. abortus with the bile salt TUDCA, a chemical used to mitigate the effects of ER stress, they observed dramatically damped inflammation in the placenta, and increased survival of newborn pups, without a change in the bacterial burden. B. abortus is usually transmitted between animals when a pregnant female becomes infected, develops placental inflammation and has a spontaneous abortion, releasing the infected uterine contents. Animals grazing nearby subsequently eat these infected tissues and become infected. The finding that B. abortus secretes a protein that actively triggers placental inflammation suggests that it may be hijacking a host inflammatory pathway to promote its transmission to the next host. The mechanism by which IRE1α promotes inflammatory signalling remains unresolved. The authors propose a simple model in which IRE1α stimulation leads to the formation of a complex between TRAF2 (a ubiquitin ligase enzyme that binds to IRE1α), NOD1 and NOD2 (Fig. 1). This then leads to RIP2 activation, presumably by promoting interactions between these proteins. Although this is consistent with the requirement for TRAF2, NODs and RIP2 for inflammatory responses, the question of how the NOD receptors would be activated in the absence of bacterium-derived ligands remains untested. Although NODs have long been known to have a role in peptidoglycan sensing, only more recently have data emerged showing that peptidoglycan can directly bind NOD proteins9. It is possible that the peptidoglycan-independent signalling triggered by ER stress activates NODs through a distinct biochemical mechanism. An intriguing alternative possibility is that host-derived ligands are generated in response to ER stress, and activate NOD receptors in the cytoplasm. Despite these uncertainties, Keestra-Gounder and colleagues' work compels researchers in the field to expand their thinking about the role of NODs in innate immunity beyond simply the sensing of bacterial ligands. It has long been recognized that the immune response to pathogens in plants relies in part on the monitoring of several normal host-cell physiological processes, and that disruption of these processes by a pathogen triggers an immune response10. It is now becoming increasingly evident that mammalian innate immunity also uses this strategy to 'guard' multiple cellular nodes commonly perturbed by pathogens; these include translation11, 12, membrane integrity13, mitochondrial function14, ER homeostasis3 and cytoskeletal integrity15. Strikingly, both the ER and cytoskeletal danger signals are relayed by the NODs in a ligand-independent manner, allowing NODs to participate in sensing a broad range of pathogens2, 16. This ligand-independent NOD signalling also has potential implications for human health beyond the realm of infectious diseases. Several common chronic diseases, including type 2 diabetes and inflammatory bowel disease, are associated with ER stress and inflammation5, and might be therapeutically targeted through this newly identified ER–NOD pathway.
LM Wind Power has named Reichhold as the company’s most innovative supplier in 2015. The award was presented to Reichhold for delivering new innovations that will support LM Wind Power’s growth. ‘I am so pleased that Reichhold has received this award which is great recognition for all the work that so many have contributed to advancing the UPR technology in wind energy,’ said John Gaither, CEO and president of Reichhold. ‘Both parties recognized the need to constantly improve our products, our quality and our technologies to bring about improved performance and lower costs to grow this exciting business.’ This story is reprinted from material from Reichhold, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier.
Adaptation and performance of Nesterov, FMA and FMA+ fire indices in Macurije Forest Company, Cuba [Ajuste e desempenho dos índices de perigo de incêndios nesterov, FMA e + na empresa florestal macurije, cuba]
Rodriguez M.P.R.,UPR |
Soares R.V.,Federal University of Parana |
Batista A.C.,Federal University of Parana |
Tetto A.F.,Federal University of Parana |
Floresta | Year: 2012
This research aimed to adapt Nesterov, Monte Alegre Formula (FMA) fire danger indices, and Modified Monte Alegre Formula (FMA+) to the Macurije Forest Company conditions as well as to compare their performances. The meteorological and forest fire occurrences databases were provided by the Meteorological Center, Hydro-economy Institute, and Forest Guard Corps of the Pinar del Rio province. All data referred to the period from 01/01/2006 to 31/12/2011. Two different scenarios were considered: one considering the rainfall measured at the Isabel Rubio Meteorological Station and other with the inclusion of 11 pluviometers distributed throughout the focused area. The performance of indices was evaluated by skill score methodology. Null and Low fire danger classes were considered as indicative of no fire occurrence and Medium, High and Very High classes as indicative of fire occurrence. Based on this definition the skill score and the success percentages of the indices had been calculated in the two proposed scenarios. The current and the adjusted scales of the danger indices were used. The results pointed to better performance for the three indices with the adjusted scale. The FMA+ index was the most efficient to forecast the fire danger in the focused region. The skill score and the success percentage of this index were 0.0737 and 57.10%, respectively. Source