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.     

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.     

Effect of preoperative supplementation with alpha-tocopherol and ascorbic acid on myocardial injury in patients undergoing cardiac operations

Augmentation of antioxidant defenses may help protect tissues against ischemia-reperfusion injury associated with operations involving cardiopulmonary bypass. In this study we examined the effect of pretreating patients with alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the myocardium. Seventy-six subjects undergoing elective coronary artery bypass grafting participated in a prospective, double-blind, placebo-controlled randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70% after the operation in the supplemented group and to negligible levels in the placebo group. There were no significant differences between the groups with respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the reduction of the myocardial perfusion defect determined by thallium 201 uptake. Electrocardiography provided no evidence of a benefit from antioxidant supplementation. Thus the supplementation regimen prevented the depletion of the primary lipid soluble antioxidant in plasma, but provided no measurable reduction in myocardial injury after the operation.     

Differential transforming growth factor-beta secretion in adenocarcinoma and squamous cell carcinoma of the uterine cervix

Tumor cells from eight freshly isolated cervical cancers (i.e., four adenocarcinomas and four squamous carcinomas) were analyzed for their production of the immune-inhibitory cytokine transforming growth factor-beta (TGF-beta) in vitro. All fresh adenocarcinomas secreted significant levels of TGF-beta (mean 397, range between 207 and 782 pg/ml/10(5) cells/48 hr). In contrast, no detectable TGF-beta was present in the supernatants from the four fresh squamous carcinoma cultures (P < 0.001). These data suggest that major differences in the secretion of the immunoinhibitory cytokine TGF-beta exist between squamous cell carcinomas and adenocarcinomas of the uterine cervix. Furthermore, these findings suggest that at least some of the differences in the natural biologic behavior, as well as in the response to radiation treatment, between these two histologic types of cervical cancer could be related to differences in secretion of this immune-inhibitory cytokine.     

Effect of transluminal angioplasty on cerebral blood flow in the management of symptomatic vasospasm following aneurysmal subarachnoid hemorrhage

In this study the authors have examined the effects of transluminal angioplasty on cerebral blood flow (CBF) in the management of intractable vasospasm following aneurysmal subarachnoid hemorrhage (SAH). Fourteen consecutively enrolled patients underwent attempted angioplasty with or without intraarterial infusion of papaverine. Twelve patients underwent pre- and postangioplasty xenon-enhanced computerized tomography (Xe-CT) scanning to measure regional CBF in 55 to 65 regions of interest (ROIs) per patient. Angioplasty was possible in 13 (93%) of 14 patients, with angiographically demonstrated improvement in all 13. Twelve (92%) of the 13 patients were neurologically improved following angioplasty; seven (58%) of the 12 patients who improved had a complete reversal of all delayed ischemic deficits. Angioplasty significantly decreased the mean number of ROIs at risk (11.4 ROIs pre- and 0.9 ROIs postangioplasty) (p < 0.00005, t-test). All patients had a reduction in the number of ROIs at risk after angioplasty; six (50%) of 12 no longer had any ROIs remaining at risk after angioplasty. Angioplasty significantly increased the mean CBF within at-risk ROIs (13 ml/100 g/minute pre- and 44 ml/100 g/minute postangioplasty) (p < 0.00005, t-test). All patients experienced an improvement in mean CBF in at-risk ROIs after angioplasty, with the mean CBF improving to above 20 ml/100 g/minute in all cases. No differences in the degree of improvement were found in patients who received intraarterial papaverine compared with those who did not. In the majority of patients with refractory vasospasm following SAH, angioplasty effectively dilated spastic arteries, reversed delayed neurological deficits, and significantly improved CBF in areas of brain at risk of infarction.     

Effects of the glucocorticoid agonist, RU28362, and the antagonist RU486 on lung phosphatidylcholine and antioxidant enzyme development in the genetically obese Zucker rat

The biochemical maturation of the lung in late gestation and in the young animal is regulated by glucocorticoids. The present study was aimed at dissociating the different glucocorticoid receptor sites involved in these regulatory functions. The obese Zucker rat was selected as a model for this study as it exhibits hypersensitivity to glucocorticoid hormone action by virtue of its elevated receptor numbers and activity. Two synthetic steroid analogues were administered to obese animals; RU28362, a specific type II receptor agonist, and the type II antagonist RU486. RU28362 promoted a strong catabolic effect, which was associated with reduced food intake and the abolition of growth in the rats. The agonist, RU28362, attenuated developmental increases in antioxidant enzyme activities, and altered the growth of the tissue. At the age studied, development of the lung phosphatidylcholine (PC) system was almost complete, but RU28362 increased disaturated PC 16:0/16:0 concentrations by almost 2-fold, and altered the molecular composition of total pulmonary PC. RU486 attenuated the growth of the rats and reduced their food intake. Treatment with the type II antagonist attenuated lung growth and increased the activities of pulmonary copper zinc (Cu/Zn) and manganese (Mn) superoxide dismutases. RU486 had no effect on lung PC concentrations and molecular composition. The data suggest a role for type I glucocorticoid receptors in the regulation of the antioxidant enzyme system in the lung, as type II antagonism will channel endogenous glucocorticoid binding to the type I site. Type II receptor binding would appear to play a role in regulating the lung PC content.