The modular systems biology approach to investigate the control of apoptosis in Alzheimer's disease neurodegeneration

Apoptosis is a programmed cell death that plays a critical role during the development of the nervous system and in many chronic neurodegenerative diseases, including Alzheimer's disease (AD). This pathology, characterized by a progressive degeneration of cholinergic function resulting in a remarkable cognitive decline, is the most common form of dementia with high social and economic impact. Current therapies of AD are only symptomatic, therefore the need to elucidate the mechanisms underlying the onset and progression of the disease is surely needed in order to develop effective pharmacological therapies. Because of its pivotal role in neuronal cell death, apoptosis has been considered one of the most appealing therapeutic targets, however, due to the complexity of the molecular mechanisms involving the various triggering events and the many signaling cascades leading to cell death, a comprehensive understanding of this process is still lacking. Modular systems biology is a very effective strategy in organizing information about complex biological processes and deriving modular and mathematical models that greatly simplify the identification of key steps of a given process. This review aims at describing the main steps underlying the strategy of modular systems biology and briefly summarizes how this approach has been successfully applied for cell cycle studies. Moreover, after giving an overview of the many molecular mechanisms underlying apoptosis in AD, we present both a modular and a molecular model of neuronal apoptosis that suggest new insights on neuroprotection for this disease

PI16 is a shear stress and inflammation-regulated inhibitor of MMP2

Raised endothelial shear stress is protective against atherosclerosis but such protection may be lost at sites of inflammation. We found that four splice variants of the peptidase inhibitor 16 (PI16) mRNA are among the most highly shear stress regulated transcripts in human coronary artery endothelial cells (HCAECs), in vitro but that expression is reduced by inflammatory mediators TNFα and IL-1β. Immunohistochemistry demonstrated that PI16 is expressed in human coronary endothelium and in a subset of neointimal cells and medial smooth muscle cells. Adenovirus-mediated PI16 overexpression inhibits HCAEC migration and secreted matrix metalloproteinase (MMP) activity. Moreover, PI16 inhibits MMP2 in part by binding an exposed peptide loop above the active site. Our results imply that, at high endothelial shear stress, PI16 contributes to inhibition of protease activity; protection that can be reversed during inflammation

An Efficient Real-Time Data Dissemination Multicast Protocol for Big Data in Wireless Sensor Networks

© 2018, Springer Nature B.V. As data source for Big Data, wireless sensor networks play great role in data collection and dissemination. Specially, real-time communication remains one of the crucial research challenges, because of the high complexity and severe networking requirements on restrained node in wireless sensor networks. Moreover, current schemes are assumed to take general traffic model for real-time delivery so they lack adaptability. To solve this problem, few routing protocols have been designed to accommodate new real-time model, (m,k)-firm, which is regarded as the most applicable scheme for event as well as query based applications in wireless sensor networks. However, since current schemes for (m,k)-firm stream are proposed to support unicast communications only, they cannot be applied to multicast communications where many group members are willing to receive data packets from the sink node. To overcome this problem, we propose a new multicast scheme for (m,k)-firm stream to deliver data packet to group members. To construct a multicast tree, different types of overlay tree are constructed according to distance based priority (DBP) value. Simulation results prove that the proposed scheme can meet (m,k)-firm requirement and have longer network lifetime than existing schemes