Massive glycosaminoglycan-dependent entry of Trp-containing cell-penetrating peptides induced by exogenous sphingomyelinase or cholesterol depletion

Among non-invasive cell delivery strategies, cell-penetrating peptide (CPP) vectors represent interesting new tools. To get fundamental knowledge about the still debated internalisation mechanisms of these peptides, we modified the membrane content of cells, typically by hydrolysis of sphingomyelin or depletion of cholesterol from the membrane outer leaflet. We quantified and visualised the effect of these viable cell surface treatments on the internalisation efficiency of different CPPs, among which the most studied Tat, R₉, penetratin and analogues, that all carry the N-terminal biotin-Gly₄ tag cargo. Under these cell membrane treatments, only penetratin and R₆W₃ underwent a massive glycosaminoglycan (GAG)-dependent entry in cells. Internalisation of the other peptides was only slightly increased, similarly in the absence or the presence of GAGs for R₉, and only in the presence of GAGs for Tat and R₆L₃. Ceramide formation (or cholesterol depletion) is known to lead to the reorganisation of membrane lipid domains into larger platforms, which can serve as a trap and cluster receptors. These results show that GAG clustering, enhanced by formation of ceramide, is efficiently exploited by penetratin and R₆W₃, which contains Trp residues in their sequence but not Tat, R₉ and R₆L₃. Hence, these data shed new lights on the differences in the internalisation mechanism and pathway of these peptides that are widely used in delivery of cargo molecules.     

Comparison of breeding biology aspects of Fluvicola nengeta (Aves: Tyrannidae) between two nesting sites

Fluvicola nengeta is an insectivorous bird that belongs to the Tyrannidae family, which lives close to bodies of water and can occur in urban areas as well. It makes use of natural and man-made substrates to build its nests. This study aims at describing the reproductive biology of F. nengeta by comparing nests built on vegetation and man-made structures as to their shapes, nest dimensions, building materials, distance from bodies of water and reproductive success. Forty-four nests were found, where 30 were located in vegetation and 14 on man-made structures. Nests did not exhibit any single pattern and were divided into three distinct shapes: closed/globular/base; closed/ovoid/base (45.5%; n = 5 for both) and low cup/base (9%; n = 1). Nests built on man-made structures exhibited a larger amount of anthropic material, such as plastic and paper, instead of plant-derived materials. Nests on man-made structures were found to be higher up from the ground (459.8 ± 46.9 m) and farther from water (232.9 ± 54.8 m) in comparison to those on vegetation (92.2 ± 28.6 m and 7.3 ± 4.7 m, respectively), aside from exhibiting a higher Mayfield reproductive success (37%) when compared to nests built on vegetation (34%). The estimated values of the daily survival rate (DSR) for vegetation nests were 0.997 for the incubation period and 0.928 for the nestling period. In man-made structure nests, DSRs were 0.968 and 0.964, respectively, during the incubation and nestling periods. The period survival rate (PSR) of nests in vegetation was significantly higher than the PSRs of nests in man-made structures during the incubation period. DSRs did not differ between incubation and nestling periods for either nesting sites.     

Short-run wavelet-based covariance regimes for applied portfolio management

Decisions on ass et allocations are often determined by covariance estimates from historical market data. In this paper, we introduce a wavelet-based portfolio algorithm, distinguishing between newly embedded news and long-run information that has already been fully absorbed by the market. Exploiting the wavelet decomposition into short- and long-run covariance regimes, we introduce an approach to focus on particular covariance components. Using generated data, we demonstrate that short-run covariance regimes comprise the relevant information for periodical portfolio management. In an empirical application to US stocks and other international markets for weekly, monthly, quarterly, and yearly holding periods (and rebalancing), we present evidence that the application of wavelet-based covariance estimates from short-run information outperforms portfolio allocations that are based on covariance estimates from historical data.     

微波辅助生物柴油生产的一体化计算

多物理场仿真动态计算对于优化微波化学加热反应体系的生产工艺,避免高功率微波带来的安全问题起到极其重要的作用.然而目前大多数微波加热化学反应的多物理场模型仅引入电磁和热传模块进行分析,且将电磁、热力学等物性参数视为常量而忽视了反应体系中各组分和温度变化对物性参数的影响,从而影响到模型的可靠性和准确性.本工作在以往模型的基础上,利用最近提出的简化且精度更高的介电系数表达式,通过引入化学反应工程和传质的计算来对电磁、热力学等物性参数随着反应体系浓度和温度的变化进行自适应实时更新,同时考虑了自然对流对传热和传质的影响.新模型避免了以往模型需要手动更新参数、介电系数表达公式复杂、热力学参数仅根据反应组分变化更新而无法获得更多化学反应模块信息、忽略液体自然对流对温度扩散的影响的弊端,实现了微波促进生物柴油生产的一体化计算.通过实验测量的温度分布验证了模型的合理性和准确性.     

The Predictive Performance Evaluation of Biased Regression Predictors With Correlated Errors

When the interdependence of disturbances is present in a regression model, the pattern of sample residuals contains information which is useful in the prediction of post‐sample drawings and when multicollinearity among regressors is also present, it is useful to use biased regression estimators. This information is exploited in the biased predictors derived here. Also, the predictive performance of various biased predictors with correlated errors is discussed and all pair‐wise comparisons are made among these predictors. The theoretical results are illustrated by a numerical example. Copyright © 2015 John Wiley & Sons, Ltd.     

Red blood cells carry out T cell growth and survival bioactivities that are sensitive to cyclosporine A

Red blood cells (RBC) have emerged as a novel regulatory cell type endowed with bioactivities toward activated human T cells. Herein we show that the RBC bioactivities act on intracellular pathways initiated by T cell receptor (TCR)-dependent and -independent stimuli, including IL-2, IL-15, and the mixture of phorbol dibutyrate and ionomycin. The RBC bioactivities preserve the antioxidant status and are capable of rescuing activated T cells from cell death induced by serum deprivation. They are not mediated by glycosylphosphatidylinositol-linked receptors or sialic acids, and kinetic studies revealed that they hasten the entrance into the cell cycle. By using cyclosporine A (CsA) and rapamycin (Rapa) we show that the RBC bioactivities are calcineurin-dependent. Thus, treatment of T cells with CsA, but not Rapa, impaired RBC bioactivities, and preincubation of RBC with CsA completely abolished their bioactivities. We have demonstrated that RBC carry out bioactivities that are sensitive to CsA.     

For whom the bell tolls? DING proteins in health and disease

DING proteins, identified mainly by their eponymous N-terminal sequences, are ubiquitous in living organisms. Amongst bacteria, they are common in pseudomonads, and have been characterised with respect to genetics and structure. They form part of a wider family of phosphate-binding proteins, with emerging roles in phosphate acquisition and pathogenicity. Many DING proteins have been isolated in eukaryotes, in which they have been associated with very diverse biological activities, often in the context of possible signalling roles. Disease states in which DING proteins have been implicated include rheumatoid arthritis, lithiasis, atherosclerosis, some tumours and tumour-associated cachexia, and bacterial and viral adherence. Complete genetic and structural characterisation of eukaryotic DING genes and proteins is still lacking, though the phosphate-binding site seems to be conserved. Whether as bacterial proteins related to bacterial pathogenicity, or as eukaryotic components of biochemical signalling systems, DING proteins require further study. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Common variants near TARDBP and EGR2 are associated with susceptibility to Ewing sarcoma

Ewing sarcoma, a pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. We performed a genome-wide association study (GWAS) of 401 French individuals with Ewing sarcoma, 684 unaffected French individuals and 3,668 unaffected individuals of European descent and living in the United States. We identified candidate risk loci at 1p36.22, 10q21 and 15q15. We replicated these loci in two independent sets of cases and controls. Joint analysis identified associations with rs9430161 (P = 1.4 × 10(-20); odds ratio (OR) = 2.2) located 25 kb upstream of TARDBP, rs224278 (P = 4.0 × 10(-17); OR = 1.7) located 5 kb upstream of EGR2 and, to a lesser extent, rs4924410 at 15q15 (P = 6.6 × 10(-9); OR = 1.5). The major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence. TARDBP shares structural similarities with EWSR1 and FUS, which encode RNA binding proteins, and EGR2 is a target gene of EWSR1-ETS. Variants at these loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2.     

The Instrument That Never Was: Inventing,Manufacturing, and Branding Réaumur's Thermometer During the Enlightenment

At the beginning of the 1730s René Antoine Ferchault de Réaumur published two long memoirs on a new type of thermometer equipped with a specially calibrated scale — known ever since as the Réaumur scale. It became one of the most common ‘standardized’ thermometers in Europe until the late nineteenth century. What made this thermometer so successful? What was it specifically? I will first argue that the real Réaumur thermometer as an instrument was a fiction, a ghost — an idealized instrument. On paper, it was theoretically flawless. In reality, the standardized Réaumur thermometer was most likely never achieved. This article shows that its success was essentially due to a recontextualisation from theoretical natural philosophy — Réaumur's principle of uniformity — to: 1) the context of artisanal knowledge and practices and 2) the context of making and reporting in the Mémoires de l'Académie royale des sciences actual measurements done in the field (in Paris at the Observatory, in Provincial France, in the Colonies, and in the rest of Europe). Réaumur's thermometer was essentially a theoretical method to which was associated a particular scale. It was the instrument's reification for market consumption and fieldwork that gave this specific type of thermometer materiality and authority. Although most Réaumur thermometers ever made were strikingly different from one another, over time the thermomètre de Réaumur designation became a brand, a seal of approval born from customary artisanal practices and cultural habitudes.