Regulatory RNAs: A Universal Language for Inter-Domain Communication

In eukaryotes, microRNAs (miRNAs) have roles in development, homeostasis, disease and the immune response. Recent work has shown that plant and mammalian miRNAs also mediate cross-kingdom and cross-domain communications. However, these studies remain controversial and are lacking critical mechanistic explanations. Bacteria do not produce miRNAs themselves, and therefore it is unclear how these eukaryotic RNA molecules could function in the bacterial recipient. In this review, we compare and contrast the biogenesis and functions of regulatory RNAs in eukaryotes and bacteria. As a result, we discovered several conserved features and homologous components in these distinct pathways. These findings enabled us to propose novel mechanisms to explain how eukaryotic miRNAs could function in bacteria. Further understanding in this area is necessary to validate the findings of existing studies and could facilitate the use of miRNAs as novel tools for the directed remodelling of the human microbiota.     

The control of sea lice in Atlantic salmon by selective breeding

Sea lice threaten the welfare of farmed Atlantic salmon and the sustainability of fish farming across the world. Chemical treatments are the major method of control but drug resistance means that alternatives are urgently needed. Selective breeding can be a cheap and effective alternative. Here, we combine experimental trials and diagnostics to provide a practical protocol for quantifying resistance to sea lice. We then combined quantitative genetics with epidemiological modelling to make the first prediction of the response to selection, quantified in terms of reduced need for chemical treatments. We infected over 1400 young fish with Lepeophtheirus salmonis, the most important species in the Northern Hemisphere. Mechanisms of resistance were expressed early in infection. Consequently, the number of lice per fish and the ranking of families were very similar at 7 and 17 days post infection, providing a stable window for assessing susceptibility to infection. The heritability of lice numbers within this time window was moderately high at 0.3, confirming that selective breeding is viable. We combined an epidemiological model of sea lice infection and control on a salmon farm with genetic variation in susceptibility among individuals. We simulated 10 generations of selective breeding and examined the frequency of treatments needed to control infection. Our model predicted that substantially fewer chemical treatments are needed to control lice outbreaks in selected populations and chemical treatment could be unnecessary after 10 generations of selection. Selective breeding for sea lice resistance should reduce the impact of sea lice on fish health and thus substantially improve the sustainability of Atlantic salmon production.     

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation.     

Within-class multimodal classification

Multimedia Tools and Applications - In many real-world classification problems there exist multiple subclasses (or clusters) within a class; in other words, the underlying data distribution is...     

Techniques for high-frequency integrated test and measurement

This paper describes techniques for the on-chip measurement of high-frequency and/or high-bandwidth electrical phenomena in ultra large-scale integration environments. The techniques rely on the integration of multiple compact and robust electronic test devices, or cores, at various locations within an integrated circuit. The cores consist primarily of signal generators that approximate the output of a sigma-delta modulator using finite repetitious bit patterns and a small set of highly robust analog components. They are capable of digitizing on-chip signals at gigahertz rates even using low-cost manufacturing processes. Simple communication between the multiple cores enables the migration of many "board-level" type measurements down to the chip level.     

Managing R&D alliances within government: the "virtual agency" concept

The virtual agency concept is now used within the United States Government as an alliance approach to manage large research and development (R&D) processes across departments. This paper examines the history of the virtual agency concept and its important characteristics. The paper identifies the potential benefits and associated risks involved in managing R&D within a virtual agency. Three cases are examined where the virtual agency concept has been applied to R&D programs: the High Performance Computing and Communications initiative, the Next Generation Internet, and the Partnership for a New Generation of Vehicles. The case studies indicate that the R&D process is attempting to balance formal process controls with the agility to adapt rapidly to new research opportunities. Virtual agencies can be used to improve organizational efficiency, improve knowledge transfer, increase interoperability through standards, provide better alignment of agency missions with national policy, and introduce increased flexibility into the R&D process. At the same time, the virtual agency concept has major risks including inefficiencies due to organizational complexity, the danger of collective myopia, the problem of adopting standards too early, the difficulty of reaching objectives in a loose organizational structure, and the problem of properly balancing the tension between agency mission objectives and national policy agendas.     

Possible anatomical basis of recovery of function after neonatal frontal lesions in rats.

Rats given medial frontal lesions on Postnatal Day 1 or Day 10 were trained on the Morris water task on Days 19–21 or Days 56–58. The operated groups were equally impaired at the water task on Days 19–21, but the Day 10 rats had recovered by 56 days. Dendritic arborization and spine density were analyzed in parietal layer II–III pyramidal cells. At Day 60, but not at Day 22, the Day 10 animals had more dendritic spines per unit dendritic length than did the controls or Day 1 rats. Thus, there was functional recovery rather than sparing after frontal lesions at 10 days, and the recovery was correlated with an increase in dendritic spines. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Effects of H2O, CO and CO2 on the H2 Permeance and Surface Characteristics of 1 mm Thick Pd80wt%Cu Membranes

The hydrogen permeance of 1 mm-thick Pd_80wt%Cu foils was measured in the presence of equimolar mixtures of H₂ with CO, CO₂ or H₂O over the temperature and total pressure ranges of 623–1,173 K and 0.62–2.86 MPa, respectively. In all cases, permeance losses at 623 and 738 K were very modest. At higher temperatures, more significant decreases in membrane permeance were observed with the highest reduction of about 50% occurring when macroscopic carbon deposition occurred on the membrane surface during H₂–CO exposure at 908 K. The more worrisome effects of exposure to these gases, however, were the micron-scale surface defects observed at 908 and 1,038 K. Although the 1 mm thick disk membranes retained their mechanical integrity, such defects could cause catastrophic failure of ultra-thin, Pd–Cu membranes (1–5 μm thick) deposited on porous substrates.