Studies in RF power communication, SAR, and temperature elevation in wireless implantable neural interfaces

Implantable neural interfaces are designed to provide a high spatial and temporal precision control signal implementing high degree of freedom real-time prosthetic systems. The development of a Radio Frequency (RF) wireless neural interface has the potential to expand the number of applications as well as extend the robustness and longevity compared to wired neural interfaces. However, it is well known that RF signal is absorbed by the body and can result in tissue heating. In this work, numerical studies with analytical validations are performed to provide an assessment of power, heating and specific absorption rate (SAR) associated with the wireless RF transmitting within the human head. The receiving antenna on the neural interface is designed with different geometries and modeled at a range of implanted depths within the brain in order to estimate the maximum receiving power without violating SAR and tissue temperature elevation safety regulations. Based on the size of the designed antenna, sets of frequencies between 1 GHz to 4 GHz have been investigated. As expected the simulations demonstrate that longer receiving antennas (dipole) and lower working frequencies result in greater power availability prior to violating SAR regulations. For a 15 mm dipole antenna operating at 1.24 GHz on the surface of the brain, 730 uW of power could be harvested at the Federal Communications Commission (FCC) SAR violation limit. At approximately 5 cm inside the head, this same antenna would receive 190 uW of power prior to violating SAR regulations. Finally, the 3-D bio-heat simulation results show that for all evaluated antennas and frequency combinations we reach FCC SAR limits well before 1 °C. It is clear that powering neural interfaces via RF is possible, but ultra-low power circuit designs combined with advanced simulation will be required to develop a functional antenna that meets all system requirements. © 2013 Zhao et al

Evidence for a Transport-Trap Mode of Drosophila melanogaster gurken mRNA Localization

The Drosophila melanogaster gurken gene encodes a TGF alpha-like signaling molecule that is secreted from the oocyte during two distinct stages of oogenesis to define the coordinate axes of the follicle cell epithelium that surrounds the oocyte and its 15 anterior nurse cells. Because the gurken receptor is expressed throughout the epithelium, axial patterning requires region-specific secretion of Gurken protein, which in turn requires subcellular localization of gurken transcripts. The first stage of Gurken signaling induces anteroposterior pattern in the epithelium and requires the transport of gurken transcripts from nurse cells into the oocyte. The second stage of Gurken signaling induces dorsovental polarity in the epithelium and requires localization of gurken transcripts to the oocyte's anterodorsal corner. Previous studies, relying predominantly on real-time imaging of injected transcripts, indicated that anterodorsal localization involves transport of gurken transcripts to the oocyte's anterior cortex followed by transport to the anterodorsal corner, and anchoring. Such studies further indicated that a single RNA sequence element, the GLS, mediates both transport steps by facilitating association of gurken transcripts with a cytoplasmic dynein motor complex. Finally, it was proposed that the GLS somehow steers the motor complex toward that subset of microtubules that are nucleated around the oocyte nucleus, permitting directed transport to the anterodorsal corner. Here, we re-investigate the role of the GLS using a transgenic fly assay system that includes use of the endogenous gurken promoter and biological rescue as well as RNA localization assays. In contrast to previous reports, our studies indicate that the GLS is sufficient for anterior localization only. Our data support a model in which anterodorsal localization is brought about by repeated rounds of anterior transport, accompanied by specific trapping at the anterodorsal cortex. Our data further indicate that trapping at the anterodorsal corner requires at least one as-yet-unidentified gurken RLE

Subcellular Distribution of Mitochondrial Ribosomal RNA in the Mouse Oocyte and Zygote

Mitochondrial ribosomal RNAs (mtrRNAs) have been reported to translocate extra-mitochondrially and localize to the germ cell determinant of oocytes and zygotes in some metazoa except mammals. To address whether the mtrRNAs also localize in the mammals, expression and distribution of mitochondrion-encoded RNAs in the mouse oocytes and zygotes was examined by whole-mount in situ hybridization (ISH). Both 12S and 16S rRNAs were predominantly distributed in the animal hemisphere of the mature oocyte. This distribution pattern was rearranged toward the second polar body in zygotes after fertilization. The amount of mtrRNAs decreased around first cleavage, remained low during second cleavage and increased after third cleavage. Staining intensity of the 12S rRNA was weaker than that of the 16S rRNA throughout the examined stages. Similar distribution dynamics of the 16S rRNA was observed in strontium-activated haploid parthenotes, suggesting the distribution rearrangement does not require a component from sperm. The distribution of 16S rRNAs did not coincide with that of mitochondrion-specific heat shock protein 70, suggesting that the mtrRNA is translocated from mitochondria. The ISH-scanning electron microscopy confirms the extra-mitochondrial mtrRNA in the mouse oocyte. Chloramphenicol (CP) treatment of late pronuclear stage zygotes perturbed first cleavage as judged by the greater than normal disparity in size of blastomeres of 2-cell conceptuses. Two-third of the CP-treated zygotes arrested at either 2-cell or 3-cell stage even after the CP was washed out. These findings indicate that the extra-mitochondrial mtrRNAs are localized in the mouse oocyte and implicated in correct cytoplasmic segregation into blastomeres through cleavages of the zygote

Florida Wireless Implantable Recording Electrodes (FWIRE) for Brain Machine Interfaces

This paper reviews on-going efforts towards the development of the Florida wireless implantable recording electrodes (FWIRE). The FWIRE microsystem platform is a fully implantable flexible substrate microelectrode array that employs state-of-the-art integrate-and-fire (IF) signal representation and wireless interface circuitry for recording neural activity from behaving rodents. The modular nature of the implantable neural recording electrode allows future enhancements to be seamlessly added to improve functionality including but not limited to rechargeability through inductive coupling, custom microelectrode arrays, higher capacity batteries, and more advanced integrated circuit technologies. This paper concentrates on custom integrated circuits such as neural interfacing amplifiers, baseband signal processing, wireless data and power interfaces, and battery management system

Allocation of distinct organ fates from a precursor field requires a shift in expression and function of gene regulatory networks

<div><p>A common occurrence in metazoan development is the rise of multiple tissues/organs from a single uniform precursor field. One example is the anterior forebrain of vertebrates, which produces the eyes, hypothalamus, diencephalon, and telencephalon. Another instance is the <i>Drosophila</i> wing disc, which generates the adult wing blade, the hinge, and the thorax. Gene regulatory networks (GRNs) that are comprised of signaling pathways and batteries of transcription factors parcel the undifferentiated field into discrete territories. This simple model is challenged by two observations. First, many GRN members that are thought to control the fate of one organ are actually expressed throughout the entire precursor field at earlier points in development. Second, each GRN can simultaneously promote one of the possible fates choices while repressing the other alternatives. It is therefore unclear how GRNs function to allocate tissue fates if their members are uniformly expressed and competing with each other within the same populations of cells. We address this paradigm by studying fate specification in the <i>Drosophila</i> eye-antennal disc. The disc, which begins its development as a homogeneous precursor field, produces a number of adult structures including the compound eyes, the ocelli, the antennae, the maxillary palps, and the surrounding head epidermis. Several selector genes that control the fates of the eye and antenna, respectively, are first expressed throughout the entire eye-antennal disc. We show that during early stages, these genes are tasked with promoting the growth of the entire field. Upon segregation to distinct territories within the disc, each GRN continues to promote growth while taking on the additional roles of promoting distinct primary fates and repressing alternate fates. The timing of both expression pattern restriction and expansion of functional duties is an elemental requirement for allocating fates within a single field.</p></div

Joint action of two RNA degradation pathways controls the timing of maternal transcript elimination at the midblastula transition in Drosophila melanogaster.

Maternally synthesized RNAs program early embryonic development in many animals. These RNAs are degraded rapidly by the midblastula transition (MBT), allowing genetic control of development to pass to zygotically synthesized transcripts. Here we show that in the early embryo of Drosophila melanogaster, there are two independent RNA degradation pathways, either of which is sufficient for transcript elimination. However, only the concerted action of both pathways leads to elimination of transcripts with the correct timing, at the MBT. The first pathway is maternally encoded, is targeted to specific classes of mRNAs through cis-acting elements in the 3'-untranslated region and is conserved in Xenopus laevis. The second pathway is activated 2 h after fertilization and functions together with the maternal pathway to ensure that transcripts are degraded by the MBT

Summary of Tsh/Tio dependent antennal transformations.

<p>(Left panel) If Tsh/Tio remain in the antennal disc, then the arista can be transformed into an ectopic eye. Similar transformations of the ventral head epidermis are also observed (not depicted). If <i>ey</i> expression is eliminated, then Tsh/Tio transform the arista into the tarsal portion of the leg. Interestingly, if <i>ey</i> expression is maintained but transcription of downstream members such as <i>eya</i> and <i>so</i> are lowered, then the arista does not take on a particular alternate fate but instead grows as head epidermal mass. (Right panel) The positions of the various transformations that are caused by the presence of Tsh/Tio in the antennal discs are depicted. Included are the on/off states of a number of eye, antennal, and head epidermal genes. Genes coded in black are in the “on” state while genes listed in grey are in the “off” state. Our results indicate that the arista–leg transformation appears to be due to the loss of <i>ss</i> rather than an up-regulation of <i>Antp</i>. The repression of antennal and head epidermal genes by Tsh/Tio appears to occur independently of the Ey/Eya/So module of the RD network.</p

Loss of Toy/Tsh in clones leads to a loss of tissue growth.

<p>(A,B) Drawings of third larval instar eye-antennal discs in which the entire eye field (dark blue), retinal progenitor region (light blue) and antennal field (purple) are demarcated. (C-F) Light microscope images of eye-antennal discs containing <i>wild type</i> (C), <i>toy RNAi</i> (D), <i>tsh RNAi</i>, and <i>toy/tsh RNAi</i> clones–all clones are marked by GFP. Anterior is to the right. (G) Comparison of clone size in the eye field, retinal progenitor domain, and antennal field. The individual loss of Toy or Tsh has no effect on the size/growth of the clone. However, the combined loss of Toy/Tsh inhibits clone growth within the progenitor region and eye field. As the expression of both genes is withdrawn from the antennal disc by the end of the first larval instar, there is no noticeable effect on clone size within the antenna. N = 15 per genotype, *P ≤ 0.1, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001 (Scale bars, <b>50</b> μm).</p

Cell death is a leading cause of the headless phenotype in <i>tsh/toy</i> mutant animals.

<p>(A-B) light microscope images of wild type second (A) and third (B) larval instar discs. Note that the DCP-1 is almost undetectable in wild type. (C-F) Light microscope images of discs showing apoptotic cells in the dorsal compartment (yellow arrows) where Toy and Tsh are removed. (A-D) <i>tub-GAL80</i>^<i>ts</i><i>; DE>toy RNAi + tsh RNAi</i> (C,D) 24hrs at 30°C (E,F) 42hrs at 30°C. (G-L) Dorsal and side views of adult heads in which expression of P35 and DIAP1 has partially restored eye and head development. (M-O) Light microscope images of eye-antennal discs showing partial restoration of the eye-antennal disc. (G,J,M) <i>DE-GAL4</i>, <i>UAS-toy RNAi</i>, <i>UAS-tsh RNAi</i>, <i>UAS-GFP</i>. (H,K,N) <i>DE-GAL4</i>, <i>UAS-toy RNAi</i>, <i>UAS-tsh RNAi</i>, <i>UAS-DIAP1</i>. (I,L,O) <i>DE-GAL4</i>, <i>UAS-toy RNAi</i>, <i>UAS-tsh RNAi</i>, <i>UAS-P35</i>. (P) Graph quantifying the degree of rescue when cell death is blocked. (N ≥ 25 in each experiment) (Scale bars, <b>50</b> μm).</p