Evidence for the Existence of Secretory Granule (Dense-Core Vesicle)-Based Inositol 1,4,5-Trisphosphate-Dependent Ca2+ Signaling System in Astrocytes

BACKGROUND: The gliotransmitters released from astrocytes are deemed to play key roles in the glial cell-neuron communication for normal function of the brain. The gliotransmitters, such as glutamate, ATP, D-serine, neuropeptide Y, are stored in vesicles of astrocytes and secreted following the inositol 1,4,5-trisphosphate (IP3)-induced intracellular Ca2+ releases. Yet studies on the identity of the IP3-dependent intracellular Ca2+ stores remain virtually unexplored. PRINCIPAL FINDINGS: We have therefore studied the potential existence of the IP3-sensitive intracellular Ca2+ stores in the cytoplasm of astrocytes using human brain tissue samples in contrast to cultured astrocytes that had primarily been used in the past. It was thus found that secretory granule marker proteins chromogranins and secretogranin II localize in the large dense core vesicles of astrocytes, thereby confirming the large dense core vesicles as bona fide secretory granules. Moreover, consistent with the major IP3-dependent intracellular Ca2+ store role of secretory granules in secretory cells, secretory granules of astrocytes also contained all three (types 1, 2, and 3) IP3R isoforms. SIGNIFICANCE: Given that the secretory granule marker proteins chromogranins and secretogranin II are high-capacity, low-affinity Ca2+ storage proteins and chromogranins interact with the IP3Rs to activate the IP3R/Ca2+ channels, i.e., increase both the mean open time and the open probability of the channels, these results imply that secretory granules of astrocytes function as the IP3-sensitive intracellular Ca2+ store

Group-Based Key Management Protocol for Energy Efficiency in Long-Lived and Large-Scale Distributed Sensor Networks

As wireless sensor networks grow, so does the need for effective security mechanisms. We propose a cryptographic key-management protocol, called energy-efficient key-management (EEKM) protocol. Using a location-based group key scheme, the protocol supports the revocation of compromised nodes and energy-efficient rekeying. The design is motivated by the observation that unicast-based rekeying does not meet the security requirements of periodic rekeying in long-lived wireless sensor networks. EEKM supports broadcast-based rekeying for low-energy key management and high resilience. In addition, to match the increasing complexity of encryption keys, the protocol uses a dynamic composition key scheme. EEKM also provides group-management protocols for secure group communication. We analyzed the energy efficiency and security of EEKM and compared it to other key-management protocols using a network simulator

Human microglial cells synthesize albumin in brain

Albumin has been implicated in Alzheimer's disease since it can bind to and transport amyloid beta, the causative agent; albumin is also a potent inhibitor of amyloid beta polymerization. In a pilot phase study of Human Brain Proteome Project, we found evidence that albumin may be synthesized in immortalized human microglial cells, human primary microglial cells, and human fetal and adult brain tissues. We also found the synthesis and secretion is enhanced upon microglial activation by Amyloid [beta]~1-42~, lipopolysaccharide treatment or human Alzheimer's brain

A Role of Canonical Transient Receptor Potential 5 Channel in Neuronal Differentiation from A2B5 Neural Progenitor Cells

Store-operated Ca2+ entry (SOCE) channels are the main pathway of Ca2+ entry in non-excitable cells such as neural progenitor cells (NPCs). However, the role of SOCE channels has not been defined in the neuronal differentiation from NPCs. Here, we show that canonical transient receptor potential channel (TRPC) as SOCE channel influences the induction of the neuronal differentiation of A2B5+ NPCs isolated from postnatal-12-day rat cerebrums. The amplitudes of SOCE were significantly higher in neural cells differentiated from proliferating A2B5+ NPCs and applications of SOCE blockers, 2-aminoethoxy-diphenylborane (2-APB), and ruthenium red (RR), inhibited their rise of SOCE. Among TRPC subtypes (TRPC1-7), marked expression of TRPC5 and TRPC6 with turned-off TRPC1 expression was observed in neuronal cells differentiated from proliferating A2B5+ NPCs. TRPC5 small interfering RNA (siRNA) blocked the neuronal differentiation from A2B5+ NPCs and reduced the rise of SOCE. In contrast, TRPC6 siRNA had no significant effect on the neuronal differentiation from A2B5+ NPCs. These results indicate that calcium regulation by TRPC5 would play a key role as a switch between proliferation and neuronal differentiation from NPCs

Mapping the <i>Shh</i> long-range regulatory domain

Coordinated gene expression controlled by long-distance enhancers is orchestrated by DNA regulatory sequences involving transcription factors and layers of control mechanisms. The Shh gene and well-established regulators are an example of genomic composition in which enhancers reside in a large desert extending into neighbouring genes to control the spatiotemporal pattern of expression. Exploiting the local hopping activity of the Sleeping Beauty transposon, the lacZ reporter gene was dispersed throughout the Shh region to systematically map the genomic features responsible for expression activity. We found that enhancer activities are retained inside a genomic region that corresponds to the topological associated domain (TAD) defined by Hi-C. This domain of approximately 900 kb is in an open conformation over its length and is generally susceptible to all Shh enhancers. Similar to the distal enhancers, an enhancer residing within the Shh second intron activates the reporter gene located at distances of hundreds of kilobases away, suggesting that both proximal and distal enhancers have the capacity to survey the Shh topological domain to recognise potential promoters. The widely expressed Rnf32 gene lying within the Shh domain evades enhancer activities by a process that may be common among other housekeeping genes that reside in large regulatory domains. Finally, the boundaries of the Shh TAD do not represent the absolute expression limits of enhancer activity, as expression activity is lost stepwise at a number of genomic positions at the verges of these domains

The Korean Bird Information System (KBIS) through open and public participation

<p>Abstract</p> <p>Background</p> <p>The importance of biodiversity conservation has been increasing steadily due to its benefits to human beings. Recently, producing and managing biodiversity databases have become much easier because of the information technology (IT) advancement. This made the general public's participation in biodiversity conservation much more practical than ever. For example, an openfree web service can be devised for a wider spectrum of people to collaborate with each other for sharing biodiversity information. Bird migration is one such area of the collaboration. Korean migratory birds are usually traceable in the important routes of the East Asian-Australia Flyway (EAAF), and they play a key role as an environmental change indicator of the Earth. Therefore, the preservation of migratory birds requires an information system which involves a broader range of voluntary and interactive knowledge network to process bird information production, circulation, and dissemination.</p> <p>Results</p> <p>The Korean Bird Information System (KBIS) aims to construct a cooperative partnership domestically and internationally through the acquisition, management, and sharing of Korean bird information involving both expert and non-expert groups. KBIS has six goals: data standard, system linkage, data diversity, utilization, bird knowledge network, and statistics. The key features of KBIS are to provide a simple search, gallery (photographs), and community to lead the participation of numerous non-experts, especially amateur bird watchers. The function of real-time observation data submission through the internet has been accomplished. It also provides bird banding database, statistics, and taxon network for experts. Especially, the statistics part provides the user with easy understanding of ecological trends of species based on the time and region.</p> <p>Conclusion</p> <p>KBIS is a tool for the conservation and management of bird diversity and ecosystem that encourages users to participate by providing the openfree data access and real-time data input web-interface. It will enhance bird knowledge networking activities locally, nationally, and internationally. In addition, it provides opportunities to enhance the public awareness for the preservation of bird diversity and species information in relevant localities through the database construction and networking activities. It can be found at <url>http://korbird.naris.go.kr</url>.</p

Perspective of mesenchymal transformation in glioblastoma.

Despite aggressive multimodal treatment, glioblastoma (GBM), a grade IV primary brain tumor, still portends a poor prognosis with a median overall survival of 12-16 months. The complexity of GBM treatment mainly lies in the inter- and intra-tumoral heterogeneity, which largely contributes to the treatment-refractory and recurrent nature of GBM. By paving the road towards the development of personalized medicine for GBM patients, the cancer genome atlas classification scheme of GBM into distinct transcriptional subtypes has been considered an invaluable approach to overcoming this heterogeneity. Among the identified transcriptional subtypes, the mesenchymal subtype has been found associated with more aggressive, invasive, angiogenic, hypoxic, necrotic, inflammatory, and multitherapy-resistant features than other transcriptional subtypes. Accordingly, mesenchymal GBM patients were found to exhibit worse prognosis than other subtypes when patients with high transcriptional heterogeneity were excluded. Furthermore, identification of the master mesenchymal regulators and their downstream signaling pathways has not only increased our understanding of the complex regulatory transcriptional networks of mesenchymal GBM, but also has generated a list of potent inhibitors for clinical trials. Importantly, the mesenchymal transition of GBM has been found to be tightly associated with treatment-induced phenotypic changes in recurrence. Together, these findings indicate that elucidating the governing and plastic transcriptomic natures of mesenchymal GBM is critical in order to develop novel and selective therapeutic strategies that can improve both patient care and clinical outcomes. Thus, the focus of our review will be on the recent advances in the understanding of the transcriptome of mesenchymal GBM and discuss microenvironmental, metabolic, and treatment-related factors as critical components through which the mesenchymal signature may be acquired. We also take into consideration the transcriptomic plasticity of GBM to discuss the future perspectives in employing selective therapeutic strategies against mesenchymal GBM