Optogenetic Activation of Dorsal Raphe Serotonin Neurons Rapidly Inhibits Spontaneous But Not Odor-Evoked Activity in Olfactory Cortex

Serotonin (5-hydroxytriptamine; 5-HT) is implicated in a variety of brain functions including not only the regulation of mood and control of behavior but also the modulation of perception. 5-HT neurons in the dorsal raphe nucleus (DRN) often fire locked to sensory stimuli, but little is known about how 5-HT affects sensory processing, especially on this timescale. Here, we used an optogenetic approach to study the effect of 5-HT on single-unit activity in the mouse primary olfactory (anterior piriform) cortex. We show that activation of DRN 5-HT neurons rapidly inhibits the spontaneous firing of olfactory cortical neurons, acting in a divisive manner, but entirely spares sensory-driven firing. These results identify a new role for serotonergic modulation in dynamically regulating the balance between different sources of neural activity in sensory systems, suggesting a possible role for 5-HT in perceptual inference.info:eu-repo/semantics/publishedVersio

Oxidation of ZrB2 SiC TaSi2 Materials at Ultra High Temperatures

ZrB2 - 20v% SiC - 20v% TaSi2 was oxidized in stagnant air for ten minute cycles for times up to 100 minutes at 1627 C and 1927 C. The sample oxidized at 1627 C showed oxidation resistance better than that of the standard ZrB2 - 20v% SiC. The sample oxidized at 1927 C, however, showed evidence of liquid phase formation and complex oxidation products. The sample exposed at 1927 C was analyzed in detail by scanning electron microprobe and wavelength dispersive spectroscopy to understand the complex oxidation and melting reactions occurring during exposure. The as hot-pressed material shows the formation of a Zr(Ta)B2 phase in addition to the three phases in the nominal composition already noted. After oxidation, the TaSi2 in the matrix was completely reacted to form Ta(Zr)C. The layered oxidation products included SiO2, ZrO2, Ta2O5, and a complex oxide containing both Zr and Ta. Likely reactions are proposed based on thermodynamic phase stability and phase morphology

A Survey of System Architecture Requirements for Health Care-Based Wireless Sensor Networks

Wireless Sensor Networks (WSNs) have emerged as a viable technology for a vast number of applications, including health care applications. To best support these health care applications, WSN technology can be adopted for the design of practical Health Care WSNs (HCWSNs) that support the key system architecture requirements of reliable communication, node mobility support, multicast technology, energy efficiency, and the timely delivery of data. Work in the literature mostly focuses on the physical design of the HCWSNs (e.g., wearable sensors, in vivo embedded sensors, et cetera). However, work towards enhancing the communication layers (i.e., routing, medium access control, et cetera) to improve HCWSN performance is largely lacking. In this paper, the information gleaned from an extensive literature survey is shared in an effort to fortify the knowledge base for the communication aspect of HCWSNs. We highlight the major currently existing prototype HCWSNs and also provide the details of their routing protocol characteristics. We also explore the current state of the art in medium access control (MAC) protocols for WSNs, for the purpose of seeking an energy efficient solution that is robust to mobility and delivers data in a timely fashion. Furthermore, we review a number of reliable transport layer protocols, including a network coding based protocol from the literature, that are potentially suitable for delivering end-to-end reliability of data transmitted in HCWSNs. We identify the advantages and disadvantages of the reviewed MAC, routing, and transport layer protocols as they pertain to the design and implementation of a HCWSN. The findings from this literature survey will serve as a useful foundation for designing a reliable HCWSN and also contribute to the development and evaluation of protocols for improving the performance of future HCWSNs. Open issues that required further investigations are highlighted

In vivo editing of the pan-endothelium by immunity evading simian adenoviral vector

Biological applications deriving from the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 site-specific nuclease system continue to impact and accelerate gene therapy strategies. Safe and effective in vivo co-delivery of the CRISPR/Cas9 system to target somatic cells is essential in the clinical therapeutic context. Both non-viral and viral vector systems have been applied for this delivery matter. Despite elegant proof-of-principle studies, available vector technologies still face challenges that restrict the application of CRISPR/Cas9-facilitated gene therapy. Of note, the mandated co-delivery of the gene-editing components must be accomplished in the potential presence of pre-formed anti-vector immunity. Additionally, methods must be sought to limit the potential of off-target editing. To this end, we have exploited the molecular promiscuities of adenovirus (Ad) to address the key requirements of CRISPR/Cas9-facilitated gene therapy. In this regard, we have endeavored capsid engineering of a simian (chimpanzee) adenovirus isolate 36 (SAd36) to achieve targeted modifications of vector tropism. The SAd36 vector with the myeloid cell-binding peptide (MBP) incorporated in the capsid has allowed selective in vivo modifications of the vascular endothelium. Importantly, vascular endothelium can serve as an effective non-hepatic cellular source of deficient serum factors relevant to several inherited genetic disorders. In addition to allowing for re-directed tropism, capsid engineering of nonhuman primate Ads provide the means to circumvent pre-formed vector immunity. Herein we have generated a SAd36. MBP vector that can serve as a single intravenously administered agent allowing effective and selective in vivo editing for endothelial target cells of the mouse spleen, brain and kidney. DATA AVAILABILITY: The data that support the findings of this study are available from the corresponding author upon reasonable request

Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research

Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation