Single-cell network biology characterizes cell-type gene regulation for drug repurposing and phenotype prediction in Alzheimer's disease

Dysregulation of gene expression in Alzheimer's disease (AD) remains elusive, especially at the cell type level. Gene regulatory network, a key molecular mechanism linking transcription factors (TFs) and regulatory elements to govern target gene expression, can change across cell types in the human brain and thus serve as a model for studying gene dysregulation in AD. However, it is still challenging to understand how cell type networks work abnormally under AD. To address this, we integrated single-cell multi-omics data and predicted the gene regulatory networks in AD and control for four major cell types, excitatory and inhibitory neurons, microglia and oligodendrocytes. Importantly, we applied network biology approaches to analyze the changes of network characteristics across these cell types, and between AD and control. For instance, many hub TFs target different genes between AD and control (rewiring). Also, these networks show strong hierarchical structures in which top TFs (master regulators) are largely common across cell types, whereas different TFs operate at the middle levels in some cell types (e.g., microglia). The regulatory logics of enriched network motifs (e.g., feed-forward loops) further uncover cell-type-specific TF-TF cooperativities in gene regulation. The cell type networks are highly modular. Several network modules with cell-type-specific expression changes in AD pathology are enriched with AD-risk genes and putative targets of approved and pending AD drugs, suggesting possible cell-type genomic medicine in AD. Finally, using the cell type gene regulatory networks, we developed machine learning models to classify and prioritize additional AD genes. We found that top prioritized genes predict clinical phenotypes (e.g., cognitive impairment). Overall, this single-cell network biology analysis provides a comprehensive map linking genes, regulatory networks, cell types and drug targets and reveals mechanisms on cell-type gene dyregulation in AD.

Ambient BackCom in Beyond 5G NOMA Networks: A Multi-Cell Resource Allocation Framework

This article proposes a new resource allocation framework that uses the dual theory approach. Specifically, the sum-rate of the multi-cell network having backscatter tags and NOMA user equipments is maximized by formulating a joint optimization problem. To find the efficient base station transmit power and backscatter reflection coefficient in each cell, the original problem is first divided into two subproblems and then derived the closed-form solutions. A comparison with the orthogonal multiple access (OMA) ambient BackCom and pure NOMA transmission has been provided.

Ambient BackCom in Beyond 5G NOMA Networks: A Multi-Cell Resource Allocation Framework

This article proposes a new resource allocation framework that uses the dual theory approach. Specifically, the sum-rate of the multi-cell network having backscatter tags and NOMA user equipments is maximized by formulating a joint optimization problem. To find the efficient base station transmit power and backscatter reflection coefficient in each cell, the original problem is first divided into two subproblems and then derived the closed-form solutions. A comparison with the orthogonal multiple access (OMA) ambient BackCom and pure NOMA transmission has been provided.

Age-Dependent Intestinal Repair: Implications for Foals with Severe Colic

Colic is a leading cause of death in horses, with the most fatal form being strangulating obstruction which directly damages the intestinal barrier. Following surgical intervention, it is imperative that the intestinal barrier rapidly repairs to prevent translocation of gut bacteria and their products and ensure survival of the patient. Age-related disparities in survival have been noted in many species, including horses, humans, and pigs, with younger patients suffering poorer clinical outcomes. Maintenance and repair of the intestinal barrier is regulated by a complex mucosal microenvironment, of which the ENS, and particularly a developing network of subepithelial enteric glial cells, may be of particular importance in neonates with colic. Postnatal development of an immature enteric glial cell network is thought to be driven by the microbial colonization of the gut and therefore modulated by diet-influenced changes in bacterial populations early in life. Here, we review the current understanding of the roles of the gut microbiome, nutrition, stress, and the ENS in maturation of intestinal repair mechanisms after foaling and how this may influence age-dependent outcomes in equine colic cases.

Duplication elimination in cache-uplink transmission over B5G small cell network

In this era of the digital world, data play a central role and are continuously challenging spectrum efficiency. With the introduction of enriched multimedia user-generated content, the challenges are even more aggravated. In this vein, uplink caching is considered as one of the promising solutions to effectively cater the user’s demands. One of the main challenges for uplink caching is duplication elimination. In this paper, a cache enabled uplink transmission with a duplication elimination scheme is proposed. The proposed scheme matches the mobile’s data to be uploaded with the cached contents both at mobile station (MS) and small base station (SBS). In contrast to existing techniques, the proposed scheme broadcasts the cached contents at an SBS to all the MSs under its footprint. This provides MS an opportunity to exploit the list of cached contents before uploading its data. A MS only uploads its data if it is not already cached at an SBS. This significantly reduces duplication before the real transmission takes place. Furthermore, the proposed technique reduces energy consumption in addition to improving spectral efficiency and network throughput. Besides, a higher caching hit ratio and lower caching miss ratio are also observed as compared to other schemes. The simulation results reveal that the proposed scheme saves 97% energy for SBS, whereas 96–100% energy is saved for MS on average.

Outage performance of downlink NOMA-aided small cell network with wireless power transfer

This article considers the outage performance of the downlink transmission for a small cell network in a heterogeneous network. Due to mobility and distribution of users, it is necessary to study massive connections and high energy efficiency for such kind of systems. To be an enabler of energy harvesting, a power beacon is helpful to support the base station to send signals to distant users, and wireless power transfer (WPT) is exploited to guarantee the data packets transmission from the power beacon to the base station. To provide massive connections, we propose a novel non-orthogonal multiple access (NOMA) technique combined with WPT to enhance outage performance and latency reduction. Furthermore, we derive outage probability (OP) to characterize the system performance. Simulation results are verified to match well between theoretical and analytical methods, and main parameters are determined to understand how they affect the proposed scheme.

T Cell Immunosenescence in Aging, Obesity, and Cardiovascular Disease

Although advances in preventive medicine have greatly improved prognosis, cardiovascular disease (CVD) remains the leading cause of death worldwide. This clearly indicates that there remain residual cardiovascular risks that have not been targeted by conventional therapies. The results of multiple animal studies and clinical trials clearly indicate that inflammation is the most important residual risk and a potential target for CVD prevention. The immune cell network is intricately regulated to maintain homeostasis. Ageing associated changes to the immune system occurs in both innate and adaptive immune cells, however T cells are most susceptible to this process. T-cell changes due to thymic degeneration and homeostatic proliferation, metabolic abnormalities, telomere length shortening, and epigenetic changes associated with aging and obesity may not only reduce normal immune function, but also induce inflammatory tendencies, a process referred to as immunosenescence. Since the disruption of biological homeostasis by T cell immunosenescence is closely related to the development and progression of CVD via inflammation, senescent T cells are attracting attention as a new therapeutic target. In this review, we discuss the relationship between CVD and T cell immunosenescence associated with aging and obesity.

Disruption of the grid cell network in a mouse model of early Alzheimer’s disease

Early-onset familial Alzheimer’s disease (AD) is marked by an aggressive buildup of amyloid beta (Aβ) proteins, yet the neural circuit operations impacted during the initial stages of Aβ pathogenesis remain elusive. Here, we report a coding impairment of the medial entorhinal cortex (MEC) grid cell network in a transgenic mouse model of familial AD that over-expresses Aβ throughout the hippocampus and entorhinal cortex. Grid cells showed reduced spatial periodicity, spatial stability, and synchrony with interneurons and head-direction cells. In contrast, the spatial coding of non-grid cells within the MEC, and place cells within the hippocampus, remained intact. Grid cell deficits emerged at the earliest incidence of Aβ fibril deposition and coincided with impaired spatial memory performance in a path integration task. These results demonstrate that widespread Aβ-mediated damage to the entorhinal-hippocampal circuit results in an early impairment of the entorhinal grid cell network.