Galectins-1 and -3 Functions in Müller Glia during Retinal Development and Degeneration

Within the retina, Müller glial cells (MGCs) are central regulators of metabolic homeostasis during normal function and during pathogenic states. MGCs are major producers of Galectins (Gal) -1 and -3, carbohydrate-binding proteins which have been found to be key regulators of various cellular processes. This study aimed to investigate the potential roles of Gal-1 and -3 during inflammatory stimuli, as well as during models of retinal development and degeneration. Treatment of MIO-M1 cells with the pro-inflammatory cytokine IL-1 resulted in significant upregulation of Gal-1 (p.05). Inhibition of Gal-3 by siRNA increased the rate of MIO-M1 cell proliferation (p<.001). TGF-β2 treatment increased the rate of migration of MIO-M1 cells (p<.01), but this effect was nullified following Gal-3 siRNA inhibition. During retinal organoid development, Gal-1 mRNA and protein expression peaked between days 10 and 30, whilst Gal-3 mRNA and protein expression increased steadily to peak at the end of the experimental period of 90 days. Using an experimental model of intraocular pressure elevation, Gal-3 protein expression was found to be upregulated in anterior chamber tissues including the iridocorneal angle and iris. Additional studies in a rodent model of optic neuropathy showed that MGC derived extracellular vesicles were effective in partially restoring retinal function at 2 weeks after treatment (p.05), for which further investigations are merited. Although the current study has provided a better understanding of the roles of Galectins during retinal development and degeneration, additional studies are warranted to elucidate the wider roles of Gal-1 and -3 during retinal degenerative diseases and explore any potential therapeutic applications of these molecules

Automated robotic liquid handling assembly of modular DNA devices

Recent advances in modular DNA assembly techniques have enabled synthetic biologists to test significantly more of the available "design space" represented by "devices" created as combinations of individual genetic components. However, manual assembly of such large numbers of devices is time-intensive, error-prone, and costly. The increasing sophistication and scale of synthetic biology research necessitates an efficient, reproducible way to accommodate large-scale, complex, and high throughput device construction. Here, a DNA assembly protocol using the Type-IIS restriction endonuclease based Modular Cloning (MoClo) technique is automated on two liquid-handling robotic platforms. Automated liquid-handling robots require careful, often times tedious optimization of pipetting parameters for liquids of different viscosities (e.g. enzymes, DNA, water, buffers), as well as explicit programming to ensure correct aspiration and dispensing of DNA parts and reagents. This makes manual script writing for complex assemblies just as problematic as manual DNA assembly, and necessitates a software tool that can automate script generation. To this end, we have developed a web-based software tool, http://mocloassembly.com, for generating combinatorial DNA device libraries from basic DNA parts uploaded as Genbank files. We provide access to the tool, and an export file from our liquid handler software which includes optimized liquid classes, labware parameters, and deck layout. All DNA parts used are available through Addgene, and their digital maps can be accessed via the Boston University BDC ICE Registry. Together, these elements provide a foundation for other organizations to automate modular cloning experiments and similar protocols. The automated DNA assembly workflow presented here enables the repeatable, automated, high-throughput production of DNA devices, and reduces the risk of human error arising from repetitive manual pipetting. Sequencing data show the automated DNA assembly reactions generated from this workflow are ~95% correct and require as little as 4% as much hands-on time, compared to manual reaction preparation

The Distribution of Alpha Elements in Ultra-Faint Dwarf Galaxies

The Milky Way ultra-faint dwarf galaxies (UFDs) contain some of the oldest, most metal-poor stars in the Universe. We present [Mg/Fe], [Si/Fe], [Ca/Fe], [Ti/Fe], and mean [alpha/Fe], abundance ratios for 61 individual red giant branch stars across 8 UFDs. This is the largest sample of alpha abundances published to date in galaxies with absolute magnitudes M_V > -8, including the first measurements for Segue 1, Canes Venatici II, Ursa Major I, and Leo T. Abundances were determined via medium-resolution Keck/DEIMOS spectroscopy and spectral synthesis. The sample spans the metallicity range -3.4 < [Fe/H] < -1.1. With the possible exception of Segue 1 and Ursa Major II, the individual UFDs show on average lower [alpha/Fe] at higher metallicities, consistent with enrichment from Type Ia supernovae. Thus even the faintest galaxies have undergone at least a limited level of chemical self-enrichment. Together with recent photometric studies, this suggests that star formation in the UFDs was not a single burst, but instead lasted at least as much as the minimum time delay of the onset of Type Ia supernovae (~100 Myr) and less than ~2 Gyr. We further show that the combined population of UFDs has an [alpha/Fe] abundance pattern that is inconsistent with a flat, Galactic halo-like alpha abundance trend, and is also qualitatively different from that of the more luminous CVn I dSph, which does show a hint of a plateau at very low [Fe/H].Comment: 14 pages, 6 figures, re-submitted to ApJ with revisions based on referee repor

Foreign Currency for Long-Term Investors

Conventional wisdom holds that conservative investors should avoid exposure to foreign currency risk. Even if they hold foreign equities, they should hedge the currency exposure of these positions and should hold only domestic Treasury bills. This paper argues that the conventional wisdom may be wrong for long-term investors. Domestic bills are risky for long-term investors, because real interest rates vary over time and bills must be rolled over at uncertain future interest rates. This risk can be hedged by holding foreign currency if the domestic currency tends to depreciate when the domestic real interest rate falls, as implied by the theory of uncovered interest parity. Empirically this effect is important and can lead conservative long-term investors to hold more than half their wealth in foreign currency.

A Note on a Result of Makowski

In this note, we fix a gap in a proof of the first author that 28 is the only even perfect number which is the sum of two perfect cubes. We also discuss the situation for higher powers

Thermal Recovery of Multi-Limbed Robots with Electric Actuators

The problem of finding thermally minimizing configurations of a humanoid robot to recover its actuators from unsafe thermal states is addressed. A first-order, data-driven, effort based, thermal model of the robots actuators is devised, which is used to predict future thermal states. Given this predictive capability, a map between configurations and future temperatures is formulated to find what configurations, subject to valid contact constraints, can be taken now to minimize future thermal states. Effectively, this approach is a realization of a contact-constrained thermal inverse-kinematics (IK) process. Experimental validation of the proposed approach is performed on the NASA Valkyrie robot hardware