The p38MAPK-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission

© Copyright © 2021 Beamer and Corrêa. p38 is a mitogen-activated protein kinase (MAPK), that responds primarily to stress stimuli. p38 has a number of targets for phosphorylation, including MAPK-activated protein kinase 2 (MK2). MK2 primarily functions as a master regulator of RNA-binding proteins, indirectly controlling gene expression at the level of translation. The role of MK2 in regulating the synthesis of pro-inflammatory cytokines downstream of inflammation and cellular stress is well-described. A significant amount of evidence, however, now points to a role for the p38MAPK-MK2 signaling axis in mediating synaptic plasticity through control of AMPA receptor trafficking and the morphology of dendritic spines. These processes are mediated through control of cytoskeletal dynamics via the activation of cofilin-1 and possibly control of the expression of Arc/Arg3.1. There is evidence that MK2 is necessary for group I metabotropic glutamate receptors long-term depression (mGluR-LTD). Disruption of this signaling may play an important role in mediating cognitive dysfunction in neurological disorders such as fragile X syndrome and Alzheimer’s disease. To date, the role of neuronal MK2 mediating synaptic plasticity in response to inflammatory stimuli has not yet been investigated. In immune cells, it is clear that MK2 is phosphorylated following activation of a broad range of cell surface receptors for cytokines and other inflammatory mediators. We propose that neuronal MK2 may be an important player in the link between inflammatory states and dysregulation of synaptic plasticity underlying cognitive functions. Finally, we discuss the potential of the p38MAPK-MK2 signaling axis as target for therapeutic intervention in a number of neurological disorders

Empat Koreografer Tari Kontemporer Indonesia Periode 1990-2008

 Penelitian ini membahas empat koreografer, dalam membuka wacana proses ketubuhan penari di Indonesia. Empat koreografer tersebut, Martinus Miroto, Mugiyono Kasido, Hartati, dan Jecko Siompo, memperlihatkan betapa kompleksitas proses ketubuhan mereka berbeda dengan penari dan koreografer pada umumnya, terutama dari luar Indonesia. Mereka mem- berikan pengalaman yang detail tentang pendisiplinan tubuh mereka untuk mencapai sebuah capaian dan keunggulan. Dengan kompleksitas disiplin dan training ketubuhan, keempat penari dan koreografer ini menggukuhkan betapa proses pencapaian dan kemuktahiran tubuh terletak pada beberapa proses penting: Training, Latihan, dan Pementasan. Jika ditilik secara ke- seluruhan, keempat penari ini mempunyai pengalaman belajar, atau setidaknya pernah men- galami proses menari bersama Sardono W. Kusumo. Ketubuhan yang yang dieksplorasi adalah ciri khas dari Sardono yang dikenal dengan laku dalam bahasa Jawa. Walaupun belajar dari Sar- dono, keempat koreografer tersebut mengembangkan tarian yang berbeda dengan Sardono.

DEMAND BASED RELIABILITY:APROPOSED MEASUREMENTAPPROACH

ABSTRACT: Significant change is taking place in the power generation market. We are witnessing structural change as we move to a deregulated and competitive global market. And we can also see significant technological change, as new products are driven towards improved efficiencies, greater output and environmental friendliness. Measuring the impact of these changes in terms of efficiency, output and reduced emissions is a straightforward exercise, and the ability to judge if the change has been positive is relatively objective. However, these structural and technological changes have created challenges in terms of reliability and availability measurements. • First, our measurement approach is obsolete and has no consideration for duty cycle... The demand, the mission profile, which must be achieved for the unit to meet its economic contribution value, is the single most important issue for power producers today • Second, if the measurements have no consideration for the demand that the unit must meet, then the measure is not tied to the profitability of the plant, and therefore the operators are forced to use non-standard measures to accommodate management reporting. • And third, the strong relationship between effective plant operations and profitability demands "real time" data gathering from the unit control or plant DCS, and transformation of the data points into meaningful information for effective decision support, specifically related to the availability and reliability o f systems, components, and the full plant, with a specific focus on measuring "demand" based availability and reliability. This paper addresses the issue and the opportunities associated with developing both new standard for measuring demand related reliability and availability, as well as the focus on "real time" data capture

The role of Matriptase-2 during the early postnatal development in humans

Hepcidin is the hepatic peptide hormone, which regulates the systemic iron homeostasis by degrading the only cellular iron exporter ferroportin. The transmembrane serine protease matriptase-2 (MT-2, encoded by TMPRSS6) is a major hepcidin inhibitor and mutations in TMPRSS6 gene are responsible of inherited iron refractory iron deficiency anemia (IRIDA), characterized by hypochromic microcytic anemia, low transferrin saturation and inappropriate normal/high levels of hepcidin. In this study we retrospectively analyzed the hematological parameters in the (neo) perinatal period of IRIDA patients to understand the role of matriptase-2 at birth and during early development. We found that anemia is not present at birth and thus we inferred that it is absent also in utero but develops after the second month of life. Our results might have implications to better understand iron homeostasis during early development in IRIDA patients and indicate that Mt2 is dispensable during fetal and neonatal life in humans, consistent with the idea that the downregulation of hepcidin by Mt2 becomes effective only with the introduction of dietary iron

Role of carbon allocation efficiency in the temperature dependence of autotroph growth rate

To predict how plant growth rate will respond to temperature requires understanding how temperature drives the underlying metabolic rates. Although past studies have considered the temperature dependences of photosynthesis and respiration rates underlying growth, they have largely overlooked the temperature dependence of carbon allocation efficiency. By combining a mathematical model that links exponential growth rate of a population of photosynthetic cells to photosynthesis, respiration, and carbon allocation; to an experiment on a freshwater alga; and to a database covering a wide range of taxa, we show that allocation efficiency is crucial for predicting how growth rates will respond to temperature change across aquatic and terrestrial autotrophs, at both short and long (evolutionary) timescales

Nutritive value of Quercus pyrenaica Willd browse species in NE of Portugal

Quercus pyrenaica Willd (pyrenean oak) occurs in a transition between the Mediterranean sclerophyllous and the temperate deciduous forest, being one of the most abundant and characteristic oak species in the Iberian Peninsula, due our economical and biological importance and by several services produced. The aim of this study was to assess the nutritive value of key browse species of Pyrenean oak Mediterranean Ecosystems in Trás-os-Montes region (Portugal). The study was to undertake at different mature stages the evolution of chemical composition and in vitro digestibility of shrub twigs and tree leaves. The browse species evaluated were Cytisus scoparius (L.) Link, Cytisus striatus (Hill) Rothm, Cytisus multiflorus (LHér.) Sweet, Genista falcata Brot. and Quercus pyrenaica. Tree samples were formed by foliage and shrub by mixed twigs from several specimens. Hand-samples of the different species were taken along the year seasons, in five moments of the year, begin May in late spring, July in summer, and final September in autumn, December in winter and begin March in early spring. Quercus pyrenaica was sampled only during the leaf production periods in five moments too. The dates were: May, July, August, September, and October; regarding different stages of leaves: very young leaf, young leaf, mature leaf, leaf in early of senescence, senescent leaf. Species varied widely in crude protein content (CP) (10.06-22.57 gKg-1 DM), neutral detergent fibre content (NDF) (36.03-66.53 gKg-1 DM), acid detergent fibre content (ADF) (24.22-53.50 gKg-1 DM), acid detergent lignin content (6.20-15.76 gKg-1 DM) and in vitro digestible organic matter (IVOMD) (39.21-70.39 %). Cytisus sp. showed the higher CP and IVOMD values. Shrub species showed the highest nutritive value in late spring and the lowest values in autumn. Oak leaves presented a constant composition along the leaf cycle just, this pattern changed in very young leaf stages when leaves were not formed

Estimation Without Representation: Early Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence Studies and the Path Forward

The recent development and regulatory approval of a variety of serological assays indicating the presence of antibodies against se-vere acute respiratory syndrome coronavirus 2 has led to rapid and widespread implementation of seroprevalence studies. Accurate estimates of seroprevalence are needed to model transmission dynamics and estimate mortality rates. Furthermore, seropreva-lence levels in a population help guide policy surrounding reopening efforts. The literature to date has focused heavily on issues surrounding the quality of seroprevalence tests and less on the sampling methods that ultimately drive the representativeness of resulting estimates. Seroprevalence studies based on convenience samples are being reported widely and extrapolated to larger popu-lations for the estimation of total coronavirus disease 2019 (COVID-19) infections, comparisons of prevalence across geographic regions, and estimation of mortality rates. In this viewpoint, we discuss the pitfalls that can arise with the use of convenience samples and offer guidance for moving towards more representative and timely population estimates of COVID-19 seroprevalence

The nasal delivery of nanoencapsulated statins – An approach for brain delivery

© 2016 Clementino et al. Purpose: Along with their cholesterol-lowering effect, statins have shown a wide range of pleiotropic effects potentially beneficial to neurodegenerative diseases. However, such effects are extremely elusive via the conventional oral administration. The purpose of the present study was to prepare and characterize the physicochemical properties and the in vivo biodistribution of simvastatin-loaded lecithin/chitosan nanoparticles (SVT-LCNs) suitable for nasal administration in view of an improved delivery of the statins to the brain. Materials and methods: Chitosan, lecithin, and different oil excipients were used to prepare nanocapsules loaded with simvastatin. Particle size distribution, surface charge, structure, simvastatin loading and release, and interaction with mucus of nanoparticles were determined. The nanoparticle nasal toxicity was evaluated in vitro using RPMI 2651 nasal cell lines. Finally, in vivo biodistribution was assessed by gamma scintigraphy via Tc99m labeling of the particles. Results: Among the different types of nanoparticles produced, the SVT-LCN_MaiLab showed the most ideal physicochemical characteristics, with small diameter (200 nm), positive surface charge (+48 mV) and high encapsulation efficiency (EE; 98%). Size distribution was further confirmed by nanoparticle tracking analysis and electron microscopy. The particles showed a relatively fast release of simvastatin in vitro (35.6%±4.2% in 6 hours) in simulated nasal fluid. Blank nanoparticles did not show cytotoxicity, evidencing that the formulation is safe for nasal administration, while cytotoxicity of simvastatin-loaded nanoparticles (IC50) was found to be three times lower than the drug solution (9.92 vs 3.50 μM). In rats, a significantly higher radioactivity was evidenced in the brain after nasal delivery of simvastatin-loaded nanoparticles in comparison to the administration of a similar dose of simvastatin suspension. Conclusion: The SVT-LCNs developed presented some of the most desirable characteristics for mucosal delivery, that is, small particle size, positive surface charge, long-term stability, high EE, and mucoadhesion. In addition, they displayed two exciting features: First was their biodegradability by enzymes present in the mucus layer, such as lysozyme. This indicates a new Trojan-horse strategy which may enhance drug release in the proximity of the nasal mucosa. Second was their ability to enhance the nose-to-brain transport as evidenced by preliminary gamma scintigraphy studies