Sonic hedgehog promotes rod photoreceptor differentiation in mammalian retinal cells in vitro.

Journal ArticleThe hedgehog gene family encodes secreted proteins important in many developmental patterning events in both vertebrates and invertebrates. In the Drosophila eye disk, hedgehog controls the progression of photoreceptor differentiation in the morphogenetic furrow. To investigate whether hedgehog proteins are also involved in the development of the vertebrate retina at stages of photoreceptor differentiation, we analyzed expression of the three known vertebrate hedgehog genes. We found that Sonic hedgehog and Desert hedgehog are expressed in the developing retina, albeit at very low levels, whereas Indian hedgehog (Ihh) is expressed in the developing and mature retinal pigmented epithelium, beginning at embryonic day 13. To determine whether hedgehog proteins have activities on developing retinal cells, we used an in vitro system in which much of retinal histogenesis is recapitulated. N-terminal recombinant Sonic Hedgehog protein (SHH-N) was added to rat retinal cultures for 3-12 d, and the numbers of retinal cells of various phenotypes were analyzed by immunohistochemistry. We found that SHH-N caused a transient increase in the number of retinal progenitor cells, and a 2- to 10-fold increase in the number of photoreceptors differentiating in the cultures when analyzed with three different photoreceptor-specific antigens. In contrast, the numbers of retinal ganglion cells and amacrine cells were similar to those in control cultures. These results show that Hedgehog proteins can regulate mitogenesis and photoreceptor differentiation in the vertebrate retina, and Ihh is a candidate factor from the pigmented epithelium to promote retinal progenitor proliferation and photoreceptor differentiation

Hyperinsulinemia-euglycemia therapy: a useful tool in treating calcium channel blocker poisoning

Hyperinsulinemia-euglycemia (HIE) therapy, when initiated promptly and aggressively, may offer considerable advantages in the treatment of calcium channel blocker poisoning. Although its mechanism of action is uncertain, HIE improves the efficiency with which the poisoned myocardium uses metabolic fuel, the end result of which is improvements in inotropy and other cardiovascular parameters. Although HIE is not universally accepted, the reports included in the previous issue of Critical Care should prompt clinicians to consider HIE an appropriate therapy specifically for calcium channel blocker poisoning

More Than a Feeling: Learning to Grasp and Regrasp using Vision and Touch

For humans, the process of grasping an object relies heavily on rich tactile feedback. Most recent robotic grasping work, however, has been based only on visual input, and thus cannot easily benefit from feedback after initiating contact. In this paper, we investigate how a robot can learn to use tactile information to iteratively and efficiently adjust its grasp. To this end, we propose an end-to-end action-conditional model that learns regrasping policies from raw visuo-tactile data. This model -- a deep, multimodal convolutional network -- predicts the outcome of a candidate grasp adjustment, and then executes a grasp by iteratively selecting the most promising actions. Our approach requires neither calibration of the tactile sensors, nor any analytical modeling of contact forces, thus reducing the engineering effort required to obtain efficient grasping policies. We train our model with data from about 6,450 grasping trials on a two-finger gripper equipped with GelSight high-resolution tactile sensors on each finger. Across extensive experiments, our approach outperforms a variety of baselines at (i) estimating grasp adjustment outcomes, (ii) selecting efficient grasp adjustments for quick grasping, and (iii) reducing the amount of force applied at the fingers, while maintaining competitive performance. Finally, we study the choices made by our model and show that it has successfully acquired useful and interpretable grasping behaviors.Comment: 8 pages. Published on IEEE Robotics and Automation Letters (RAL). Website: https://sites.google.com/view/more-than-a-feelin

Effects of Tidal Forces on the Minimum Energy Configurations of the Full Three Body Problem

We investigate the evolution of minimum energy configurations for the Full Three Body Problem (3BP). A stable ternary asteroid system will gradually become unstable due to the Yarkovsky-O’Keefe-Radzievskii-Paddack (YORP) effect and an unpredictable trajectory will ensue. Through the interaction of tidal torques, energy in the system will dissipate in the form of heat until a stable minimum energy configuration is reached. We present a simulation that describes the dynamical evolution of three bodies under the mutual effects of gravity and tidal torques. Simulations show that bodies do not get stuck in local minima and transition to the predicted minimum energy configuration

Case Management & Medication Addiction Treatment for Individuals Leaving Jail: The Bridge/El Puente Program in Hampden County

The Bridge/El Puente program will serve 300 newly released inmates from the Hampden County Correctional Center (HCCC) over 3 years. Inmates have a history of opiate and/or alcohol addiction, and are at high risk or are diagnosed with HIV or HCV. HCCC is now offering medication assisted treatment (MAT), extended release naltrexone (Vivitrol), buprenorphine and methadone, prior to release. Bi-cultural/bi-lingual case managers help inmates to continue or to start MAT once back in the community. This includes bridge prescriptions, addressing insurance issues, setting up first appointment and logistical help with getting to MAT appointments. Additionally, Bridge case managers address the often-large array of other needs newly released people struggle with upon return to the community. Bridge/El Puente is funded by SAMHSA/CSAT. In our second year, we recently obtained IRB approval to examine differences in outcomes between inmates who choose buprenorphine, naltrexone or methadone prior to release from jail and those who reject/are not offered MAT prior to release despite having an opioid use disorder. While many do start MAT once back in the community, we are interested in understanding whether initiation of MAT while in jail significantly improves outcomes

Cyclin D1 fine-tunes the neurogenic output of embryonic retinal progenitor cells

<p>Abstract</p> <p>Background</p> <p>Maintaining the correct balance of proliferation versus differentiation in retinal progenitor cells (RPCs) is essential for proper development of the retina. The cell cycle regulator cyclin D1 is expressed in RPCs, and mice with a targeted null allele at the cyclin D1 locus (<it>Ccnd1</it>^-/-) have microphthalmia and hypocellular retinas, the latter phenotype attributed to reduced RPC proliferation and increased photoreceptor cell death during the postnatal period. How cyclin D1 influences RPC behavior, especially during the embryonic period, is unclear.</p> <p>Results</p> <p>In this study, we show that embryonic RPCs lacking cyclin D1 progress through the cell cycle at a slower rate and exit the cell cycle at a faster rate. Consistent with enhanced cell cycle exit, the relative proportions of cell types born in the embryonic period, such as retinal ganglion cells and photoreceptor cells, are increased. Unexpectedly, cyclin D1 deficiency decreases the proportions of other early born retinal neurons, namely horizontal cells and specific amacrine cell types. We also found that the laminar positioning of horizontal cells and other cell types is altered in the absence of cyclin D1. Genetically replacing cyclin D1 with cyclin D2 is not efficient at correcting the phenotypes due to the cyclin D1 deficiency, which suggests the D-cyclins are not fully redundant. Replacement with cyclin E or inactivation of cyclin-dependent kinase inhibitor p27Kip1 restores the balance of RPCs and retinal cell types to more normal distributions, which suggests that regulation of the retinoblastoma pathway is an important function for cyclin D1 during embryonic retinal development.</p> <p>Conclusion</p> <p>Our findings show that cyclin D1 has important roles in RPC cell cycle regulation and retinal histogenesis. The reduction in the RPC population due to a longer cell cycle time and to an enhanced rate of cell cycle exit are likely to be the primary factors driving retinal hypocellularity and altered output of precursor populations in the embryonic <it>Ccnd1</it>^-/-retina.</p