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Ashby posted an update 1 year, 3 months ago
Autophagy is crucial for neuronal integrity. Loss of key autophagic components leads to progressive neurodegeneration and structural defects in neuronal synapses. However, the molecular mechanisms regulating autophagy in the brain remain elusive. Similarly, while it is widely accepted that protein turnover is required for synaptic plasticity, the contribution of autophagy to the degradation of synaptic proteins is unknown. We find that BDNF signaling via the tropomyosin receptor kinase B (TrkB) and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway suppresses autophagy in vivo. Autophagy is differentially regulated by fasting, in different brain regions. Suppression of autophagy is required for BDNF-induced synaptic plasticity and for memory enhancement, under conditions of nutritional stress. BDNF signaling suppresses autophagy in the forebrain of adult mice. Indeed, BDNF ablation in the neural lineage causes uncontrolled increase in autophagy. In turn, increased autophagy mediates the synaptic defects caused by BDNF deficiency. Thus, fasting suppresses autophagy in regions of the mouse forebrain, thereby promoting synaptic remodeling and memory through a BDNF-regulated mechanism. We identify three key remodelers of postsynaptic densities as cargo of autophagy. Our results establish autophagy as a pivotal component of BDNF signaling, which is essential for BDNF-induced synaptic plasticity. This molecular mechanism underlies behavioral adaptations that increase fitness in times of scarcity.Pesticides are necessary to fight agricultural pests, yet they are often nonspecific, and their widespread use is a hazard to the environment and human health. The genomic era allows for new approaches to specifically target agricultural pests, based on analysis of their genome and their microbiome. We present such an approach, to combat Bactrocera oleae, a widespread pest whose impact is devastating on olive production. To date, there is no specific pesticide to control it. Herein, we propose a novel strategy to manage this pest via identifying novel pharmacological targets on the genome of its obligate endosymbiotic bacterium Candidatus Erwinia dacicola. Three genes were selected as pharmacological targets. The 3D models of the Helicase, Polymerase, and Protease-C gene products were designed and subsequently optimized by means of molecular dynamics simulations. Successively, a series of structure-based pharmacophore models were elucidated in an effort to pave the way for the efficient high-throughput virtual screening of libraries of low molecular weight compounds and thus the discovery of novel modulating agents. Our methodology provides the means to design, test, and identify highly specific pest control substances that minimize the impact of toxic chemicals on health, economy, and the environment.Over 40 million people worldwide suffer from dementia. This number is projected to exceed 110 million by 2050 because of the aging of the worldwide population, especially in lower- and middle-income countries. The most common cause of dementia is believed to be Alzheimer’s, a brain disease associated with deposition of beta-amyloid protein and hyperphosphorylation of intraneuronal tau protein leading to synaptic degradation, neuronal loss, brain circuit disruption, a range of symptoms, and eventually, if the person lives long enough, death. Over the last few decades, treatment development has focused on the deposition of beta-amyloid protein (A-beta 1-42) that is produced in the brain in huge quantities continuously and is thought to be toxic. Unfortunately, amyloid oriented therapies targeting individuals with dementia, or its prodrome mild cognitive impairment (MCI), have not been successful therapeutically even though they have been associated with reductions in amyloid. Currently, efforts are underway to deliver these therapies to individuals with very early symptoms or at risk for Alzheimer’s dementia by virtue of genetics or a brain amyloid PET scan. find more Results from these studies are expected to begin to emerge by early 2020. In the meantime, since the amyloid hypothesis has been called into question, a number of different avenues are being pursued for treatment development. These are driven in part by new findings related to the polygenic nature of Alzheimer’s as well as the interaction between this brain disease with factors such as brain vascular disease, insulin resistance, and/or brain inflammation. The expected future of AD treatment development is thought to be precision medicine.The exhaled breath condensate is a source of biomarkers with many advantages and benefits compared to other traditional sampling techniques in respiratory medicine. It is a biological product that is formed by cooling the exhaled air via its guidance through a condenser. It is characterized as a cocktail of volatile and non-volatile compounds with water being the predominant constituent. Its composition presents a non-uniformed structure as the volatile and the non-volatile compounds vary in type and ratio. All these compounds originate from the whole respiratory tract. Some of them fulfil the criteria to be characterized as biomarkers since there is a similarity between the content of the exhaled breath condensate and the respiratory tract lining fluid. In addition, the potential biomarkers of the exhaled breath condensate and those from other biological fluids are equivalent.Advantages and Disadvantages Its place in the respiratory medicine as a matrix of biomarkers relies on its various strengths. Some of them are very important and make it exceptional regarding its application, such as its totally non-invasive character and its usage in all ages, while others present a more potential action regarding its purpose such as the categorization of respiratory diseases. However, there are limitations in its application due to the lack of standardization of its conduct which can be minimized by following the official recommendations. Additional studies are needed to develop said standardization.Aim The aim of this paper is to present a brief and comprehensive picture of the sampling technique of the exhaled breath condensate, as well as the criteria to make it a preferred choice as a source of biomarkers.