Bioelectric-calcineurin signaling module regulates allometric growth and size of the zebrafish fin

AbstractThe establishment of relative size of organs and structures is paramount for attaining final form and function of an organism. Importantly, variation in the proportions of structures frequently underlies adaptive change in morphology in evolution and maybe a common mechanism underlying selection. However, the mechanism by which growth is integrated within tissues during development to achieve proper proportionality is poorly understood. We have shown that signaling by potassium channels mediates coordinated size regulation in zebrafish fins. Recently, calcineurin inhibitors were shown to elicit changes in zebrafish fin allometry as well. Here, we identify the potassium channelkcnk5bas a key player in integrating calcineurin’s growth effects, in part through regulation of the cytoplasmic C-terminus of the channel. We propose that the interaction between Kcnk5b and calcineurin acts as a signaling node to regulate allometric growth. Importantly, we find that this regulation is epistatic to inherent mechanisms instructing overall size as inhibition of calcineurin is able to bypass genetic instruction of size as seen insofand wild-type fins, however, it is not sufficient to re-specify positional memory of size of the fin. These findings integrate classic signaling mediators such as calcineurin with ion channel function in the regulation of size and proportion during growth.</jats:p

Annual Survey of Virginia Law: Property Law

This article reviews some of the more significant cases and legislation affecting Virginia property law over the past year. The Virginia Supreme Court revisited a wide range of issues, including the level of visibility to which an adverse use must rise to establish title by adverse possession. The court also revisited the steps that a mechanic\u27s lienor must take in order to protect his or her lien. Additionally, the court also explored some new issues, such as the applicability of the rule against perpetuities to a purchase option contained in a lease

FGFR2 signaling underlies p63 oncogenic function in squamous cell carcinoma

Oncogenic transcription factors drive many human cancers, yet identifying and therapeutically targeting the resulting deregulated pathways has proven difficult. Squamous cell carcinoma (SCC) is a common and lethal human cancer, and relatively little progress has been made in improving outcomes for SCC due to a poor understanding of its underlying molecular pathogenesis. While SCCs typically lack somatic oncogene-activating mutations, they exhibit frequent overexpression of the p53-related transcription factor p63. We developed an in vivo murine tumor model to investigate the function and key transcriptional programs of p63 in SCC. Here, we show that established SCCs are exquisitely dependent on p63, as acute genetic ablation of p63 in advanced, invasive SCC induced rapid and dramatic apoptosis and tumor regression. In vivo genome-wide gene expression analysis identified a tumor-survival program involving p63-regulated FGFR2 signaling that was activated by ligand emanating from abundant tumor-associated stroma. Correspondingly, we demonstrate the therapeutic efficacy of extinguishing this signaling axis in endogenous SCCs using the clinical FGFR2 inhibitor AZD4547. Collectively, these results reveal an unanticipated role for p63-driven paracrine FGFR2 signaling as an addicting pathway in human cancer and suggest a new approach for the treatment of SCC

Development and Application of a Functional Human Esophageal Mucosa Explant Platform to Eosinophilic Esophagitis.

There is an increasing prevalence of esophageal diseases but intact human tissue platforms to study esophageal function, disease mechanisms, and the interactions between cell types in situ are lacking. To address this, we utilized full thickness human donor esophagi to create and validate the ex vivo function of mucosa and smooth muscle (n = 25). Explanted tissue was tested for contractile responses to carbachol and histamine. We then treated ex vivo human esophageal mucosa with a cytokine cocktail to closely mimic the Th2 and inflammatory milieu of eosinophilic esophagitis (EoE) and assessed alterations in smooth muscle and extracellular matrix function and stiffening. We found that full thickness human esophagus as well as the individual layers of circular and longitudinal muscularis propria developed tension in response to carbachol ex vivo and that mucosa demonstrated squamous cell differentiation. Treatment of mucosa with Th2 and fibrotic cytokines recapitulated the majority of the clinical Eosinophilic Esophagitis Diagnostic Profile (EDP) on fluidic transcriptional microarray. Transforming growth factor-beta-1 (TGFβ1) increased gene expression of fibronectin, smooth muscle actin, and phospholamban (p &lt; 0.001). The EoE cocktail also increased stiffness and decreased mucosal compliance, akin to the functional alterations in EoE (p = 0.001). This work establishes a new, transcriptionally intact and physiologically functional human platform to model esophageal tissue responses in EoE

Size dependent tunneling and optical spectroscopy of CdSe quantum rods

Photoluminescence excitation spectroscopy and scanning tunneling spectroscopy are used to study the electronic states in CdSe quantum rods that manifest a transition from a zero dimensional to a one dimensional quantum confined structure. Both optical and tunneling spectra show that the level structure depends primarily on the rod diameter and not on length. With increasing diameter, the band-gap and the excited state level spacings shift to the red. The level structure was assigned using a multi-band effective-mass model, showing a similar dependence on rod dimensions.Comment: Accepted to PRL (nearly final version). 4 pages in revtex, 4 figure

On the Properties of Two Pulses Propagating Simultaneously in Different Dispersion Regimes in a Nonlinear Planar Waveguide

Properties of two pulses propagating simultaneously in different dispersion regimes, anomalous and normal, in a Kerr-type planar waveguide are studied in the framework of the nonlinear Schroedinger equation. Catastrophic self-focusing and spatio-temporal splitting of the pulses is investigated. For the limiting case when the dispersive term of the pulse propagating in the normal dispersion regime can be neglected an indication of a possibility of a stable self-trapped propagation of both pulses is obtained.Comment: 18 pages (including 15 eps figures

Berek Rothenberg interview

An interview with Berek Rothenberg, a Holocaust survivor, conducted by Levi Smith. Berek Rothenberg was born on Jan. 3, 1921 in Sandomierz, Poland. As a boy, he belonged to several Zionist organizations including the Betar, Macabbi, and Akiva. Following the German invasion of Poland, he was taken by the Germans for forced labor on the railroads, and when released, was sent out by the Judenrat to work on a road crew. In 1942, Berek was taken away to work at the ammunition factory in Skarzysko. In 1944 he was transferred to Buchenwald and assigned to work at Schlieben, a sub camp, where the Panzerfaust was being manufactured. Berek was then transferred to Theresienstadt, where he was liberated on May 8, 1945. After liberation, he traveled around Italy waiting for a chance to move to Palestine but in 1949, Berek moved to the United States to be with his extended family.An interview with Berek Rothenberg, a survivor of the Nazi holocaust of the Jews, by Levi Smith.http://deepblue.lib.umich.edu/bitstream/2027.42/51443/5/rothenberg_b4.wavhttp://deepblue.lib.umich.edu/bitstream/2027.42/51443/4/rothenberg_b3.wavhttp://deepblue.lib.umich.edu/bitstream/2027.42/51443/3/rothenberg_b2.wavhttp://deepblue.lib.umich.edu/bitstream/2027.42/51443/2/rothenberg_b1.wavhttp://deepblue.lib.umich.edu/bitstream/2027.42/51443/1/rothenberg.pd

Moving from a Product-Based Economy to a Service-Based Economy for a More Sustainable Future

Traditionally, economic growth and prosperity have been linked with the availability, production and distribution of tangible goods as well as the ability of consumers to acquire such goods. Early evidence regarding this connection dates back to Adam Smith's Wealth of Nations (1776), in which any activity not resulting in the production of a tangible good is characterized as unproductive of any value." Since then, this coupling of economic value and material production has been prevalent in both developed and developing economies throughout the world. One unintended consequence of this coupling has been the exponential increase in the amount of solid waste being generated. The reason is that any production and consumption of material goods eventually generates the equivalent amount of (or even more) waste. Exacerbating this problem is the fact that, with today's manufacturing and supply chain management technologies, it has become cheaper to dispose and replace most products rather than to repair and reuse them. This has given rise to what some call a disposable society." To put things in perspective: In 2012 households in the U.K. generated approximately 22 thousand tons of waste, which amounted to 411 kg of waste generated per person (Department for Environment, Food & Rural Affairs, 2015). During the same time period, households in the U.S. generated 251 million tons of waste, which is equivalent to a person generating approximately 2 kg of waste every day (U.S. Environmental Protection Agency, 2012). Out of these 251 million tons of total waste generated, approximately 20% of the discarded items were categorized as durable goods. The disposal of durable goods is particularly worrisome because they are typically produced using material from non- renewable resources such as iron, minerals, and petroleum-based raw materials