REST and CoREST Modulate Neuronal Subtype Specification, Maturation and Maintenance

BACKGROUND: The repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master regulator of neuronal gene expression. REST functions as a modular scaffold for dynamic recruitment of epigenetic regulatory factors including its primary cofactor, the corepressor for element-1-silencing transcription factor (CoREST), to genomic loci that contain the repressor element-1 (RE1) binding motif. While REST was initially believed to silence RE1 containing neuronal genes in neural stem cells (NSCs) and non-neuronal cells, emerging evidence shows an increasingly complex cell type- and developmental stage-specific repertoire of REST target genes and functions that include regulation of neuronal lineage maturation and plasticity. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we utilized chromatin immunoprecipitation on chip (ChIP-chip) analysis to examine REST and CoREST functions during NSC-mediated specification of cholinergic neurons (CHOLNs), GABAergic neurons (GABANs), glutamatergic neurons (GLUTNs), and medium spiny projection neurons (MSNs). We identified largely distinct but overlapping profiles of REST and CoREST target genes during neuronal subtype specification including a disproportionately high percentage that are exclusive to each neuronal subtype. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that the differential deployment of REST and CoREST is an important regulatory mechanism that mediates neuronal subtype specification by modulating specific gene networks responsible for inducing and maintaining neuronal subtype identity. Our observations also implicate a broad array of factors in the generation of neuronal diversity including but not limited to those that mediate homeostasis, cell cycle dynamics, cell viability, stress responses and epigenetic regulation

Differential Deployment of REST and CoREST Promotes Glial Subtype Specification and Oligodendrocyte Lineage Maturation

The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation.We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes.Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Resilient Communications and Information Systems for Disaster-Preparedness using UAVs, Beacons and Data aggregators, via Delay-Tolerant Networks on Sub-GHz Frequencies

We identified use cases where resilient communications systems may help in disaster-preparedness in the Philippines. The use cases involve critical information and communications. When networks are down due to typhoons, earthquakes and other disasters, information becomes critical. By introducing low cost and easy-to-deploy communications systems, we were able to demonstrate improved information flow in post-disaster operations. We were able to gather data seamlessly and test the range of transmission in different terrains. Using multiple UAVs, we were able to demonstrate cooperative missions between ground teams and rescue teams. The systems deployed by the team improved the flow of information without the use of legacy communications networks

Application of the V-HUB Standard using LoRa Beacons, Mobile Cloud, UAVs, and DTN for Disaster-Resilient Communications

The Philippines is a country constantly visited by natural disasters. In post-disaster situations, conventional communication systems and infrastructures are likely to be disrupted, complicating rescue and relief efforts. During disaster-response scenarios, situational awareness becomes crucial for all parties involved, hence the need for disaster-resilient communication and decision-support systems. In this study, the research group developed a communication system to help in providing contextual situational awareness of survivors and a delay-tolerant network for opportunistic communication. This system employs unmanned aerial vehicles to boost the coverage of transmission and reception of this system. Development of this system used LoRa (Long Range) technology, a new communication protocol for low-powered, long range data transmission, and medium agnostic delay tolerant network (DTN) software stack. Integrated with the DTN is a decentralized near-cloud infrastructure that allow pre-positioning and in-situ allocation of digital assets and services. Outside a disaster scenario, the locals, especially those in remote areas, can use the capabilities of this system for their everyday information and communication purposes. Demonstrations were conducted both inside and outside campus to properly evaluate the performance of the system. Indoor and outdoor use-cases were simulated for various operational scenarios such as long-range detection and messaging, and detection under rubble

Demonstrations of Post-disaster Resilient Communications and Decision-Support Platform With UAVs, Ground Teams and Vehicles Using Delay-Tolerant Information Networks on Sub-GHz Frequencies

We developed an approach to a resilient communications system for post-disaster situations that make use of cooperative missions involving multiple unmanned aerial vehicles (UAV), ground teams, and vehicle communication hubs (VHUB). In this paper, we will discuss how the communication system can operate even without relying on conventional communication networks such as the cellular network and Internet, which we assume may not be available in a post-disaster scenario, by using the concept of delay-tolerant networks (DTN). By using sub-GHz radio frequencies, we can also extend the range of transmission of responder nodes from several hundred meters to a few kilometers, allowing for the ground-to-ground and ground-to-sky communications. We will also discuss and demonstrate the components of the system and several applications on victim finding, rescue, and identification. Other key capabilities of the decision support node include mapping and visualization of disaster area and victim locations, information dissemination through ad-hoc broadcast messaging, and other disaster mobile kiosk applications. We envision the technical approach discussed in this paper to eventually be deployed in future post-disaster decision-support systems based on accurate situational awareness data. Maps, videos, and other post-disaster operational information will eventually be provided to partner organizations in an effective and timely manner

Design of a tropical rain - Disaster alarm system: A new approach based on wireless sensor networks and acoustic rain rate measurements

This paper discusses the design of a broadband wireless network infrastructure which itself is a rain measurement platform for applications such as disaster alarm and sudden hazard decision management systems. A sensor testbed is setup which consists of a hybrid broadband wireless network in conjunction with real-time acoustic rain rate point sensors and complementary rain gauges. The testbed simulates the commercial deployment of a line-of-sight wireless backbone (implemented via a 26 GHz line of sight link) and broadband wireless access network at 5 GHz and 2.4 GHz. Combined wireless signal fade, acoustic power and tipping bucket rain rate measurements over a several month span indicate the feasibility of using rain-induced attenuation and fade durations to trigger imminent-hazard alerts