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Key Success Factors and Barriers for Small Businesses: Comparative Analysis

AbstractThis paper analyses the current situation of small businesses, their outlook and their problems in Europe and in Russia. The number of small businesses opened, legislative system, number of self-employed without employees, influence of bureaucratic system on small business's life, unemployment and corruption are considered in this study. The object of this paper is understanding what can modify the life of small companies. Thus the analysis of every factor is useful to understand how the economy could change, what is correct and what resolutions make the life of small businesses better. The analysis is made using data from Eurostat, Rosstat, and Fedstat (an OECD institutional website), studying how values of indicators have changed during recent years. The results clearly show that the development of small companies is correlated with the development of good institutions, a sane community and trust and optimism in economy and small business sector

Long-lived quantum coherence in photosynthetic complexes at physiological temperature

Photosynthetic antenna complexes capture and concentrate solar radiation by transferring the excitation to the reaction center which stores energy from the photon in chemical bonds. This process occurs with near-perfect quantum efficiency. Recent experiments at cryogenic temperatures have revealed that coherent energy transfer - a wavelike transfer mechanism - occurs in many photosynthetic pigment-protein complexes (1-4). Using the Fenna-Matthews-Olson antenna complex (FMO) as a model system, theoretical studies incorporating both incoherent and coherent transfer as well as thermal dephasing predict that environmentally assisted quantum transfer efficiency peaks near physiological temperature; these studies further show that this process is equivalent to a quantum random walk algorithm (5-8). This theory requires long-lived quantum coherence at room temperature, which never has been observed in FMO. Here we present the first evidence that quantum coherence survives in FMO at physiological temperature for at least 300 fs, long enough to perform a rudimentary quantum computational operation. This data proves that the wave-like energy transfer process discovered at 77 K is directly relevant to biological function. Microscopically, we attribute this long coherence lifetime to correlated motions within the protein matrix encapsulating the chromophores, and we find that the degree of protection afforded by the protein appears constant between 77 K and 277 K. The protein shapes the energy landscape and mediates an efficient energy transfer despite thermal fluctuations. The persistence of quantum coherence in a dynamic, disordered system under these conditions suggests a new biomimetic strategy for designing dedicated quantum computational devices that can operate at high temperature.Comment: PDF files, 15 pages, 3 figures (included in the PDF file

Bimodal brush-functionalized nanoparticles selective to receptor surface density.

Nanoparticles or drug carriers which can selectively bind to cells expressing receptors above a certain threshold surface density are very promising for targeting cells overexpressing specific receptors under pathological conditions. Simulations and theoretical studies have suggested that such selectivity can be enhanced by functionalizing nanoparticles with a bimodal polymer monolayer (BM) containing shorter ligated chains and longer inert protective chains. However, a systematic study of the effect of these parameters under tightly controlled conditions is still missing. Here, we develop well-defined and highly specific platforms mimicking particle-cell interface using surface chemistry to provide a experimental proof of such selectivity. Using surface plasmon resonance and atomic force microscopy, we report the selective adsorption of BM-functionalized nanoparticles, and especially, a significant enhanced selective behavior by using a BM with longer protective chains. Furthermore, a model is also developed to describe the repulsive contribution of the protective brush to nanoparticle adsorption. This model is combined with super-selectivity theory to support experimental findings and shows that the observed selectivity is due to the steric energy barrier which requires a high number of ligand-receptor bonds to allow nanoparticle adsorption. Finally, the results show how the relative length and molar ratio of two chains can be tuned to target a threshold surface density of receptors and thus lay the foundation for the rational design of BM-functionalized nanoparticles for selective targeting

Cell-type-specific modulation of innate immune signalling by vitamin D in human mononuclear phagocytes

Vitamin D is widely reported to inhibit innate immune signalling and dendritic cell (DC) maturation as a potential immunoregulatory mechanism. It is not known whether vitamin D has global or gene-specific effects on transcriptional responses downstream of innate immune stimulation, or whether vitamin D inhibition of innate immune signalling is common to different cells. We confirmed vitamin D inhibition of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signalling in monocyte-derived DC (MDDC) stimulated with lipopolysaccharide (LPS). This was associated with global but modest attenuation of LPS-induced transcriptional changes at genome-wide level. Surprisingly, vitamin D did not inhibit innate immune NF-κB activation in monocyte-derived macrophages. Consistent with our findings in MDDC, ex vivo vitamin D treatment of primary peripheral blood myeloid DC also led to significant inhibition of LPS-inducible NF-κB activation. Unexpectedly, in the same samples, vitamin D enhanced activation of both NF-κB and MAPK signalling in primary peripheral blood monocytes. In a cross-sectional clinical cohort, we found no relationship between peripheral blood vitamin D levels and LPS-inducible activation of NF-κB and MAPK pathways in monocytes of myeloid DC. Remarkably, however, in vivo supplementation of people with vitamin D deficiency in this clinical cohort also enhanced LPS-inducible MAPK signalling in peripheral blood monocytes. Therefore, we report that vitamin D differentially modulates the molecular response to innate immune stimulation in monocytes, macrophages and dendritic cells. These results are of importance in the design of studies on vitamin D supplementation in infectious and immunological diseases

Complete genome sequence of the Medicago microsymbiont Ensifer (Sinorhizobium) medicae strain WSM419

Ensifer (Sinorhizobium) medicae is an effective nitrogen fixing microsymbiont of a diverse range of annual Medicago (medic) species. Strain WSM419 is an aerobic, motile, non-spore forming, Gram-negative rod isolated from a M. murex root nodule collected in Sardinia, Italy in 1981. WSM419 was manufactured commercially in Australia as an inoculant for annual medics during 1985 to 1993 due to its nitrogen fixation, saprophytic competence and acid tolerance properties. Here we describe the basic features of this organism, together with the complete genome sequence, and annotation. This is the first report of a complete genome se-quence for a microsymbiont of the group of annual medic species adapted to acid soils. We reveal that its genome size is 6,817,576 bp encoding 6,518 protein-coding genes and 81 RNA only encoding genes. The genome contains a chromosome of size 3,781,904 bp and 3 plasmids of size 1,570,951 bp, 1,245,408 bp and 219,313 bp. The smallest plasmid is a fea-ture unique to this medic microsymbiont

Optimization and performance testing of a sequence processing pipeline applied to detection of nonindigenous species

Genetic taxonomic assignment can be more sensitive than morphological taxonomic assignment, particularly for small, cryptic or rare species. Sequence processing is essential to taxonomic assignment, but can also produce errors because optimal parameters are not known a priori. Here, we explored how sequence processing parameters influence taxonomic assignment of 18S sequences from bulk zooplankton samples produced by 454 pyrosequencing. We optimized a sequence processing pipeline for two common research goals, estimation of species richness and early detection of aquatic invasive species (AIS), and then tested most optimal models’ performances through simulations. We tested 1,050 parameter sets on 18S sequences from 20 AIS to determine optimal parameters for each research goal. We tested optimized pipelines’ performances (detectability and sensitivity) by computationally inoculating sequences of 20 AIS into ten bulk zooplankton samples from ports across Canada. We found that optimal parameter selection generally depends on the research goal. However, regardless of research goal, we found that metazoan 18S sequences produced by 454 pyrosequencing should be trimmed to 375–400 bp and sequence quality filtering should be relaxed (1.5 ≤ maximum expected error ≤ 3.0, Phred score = 10). Clustering and denoising were only viable for estimating species richness, because these processing steps made some species undetectable at low sequence abundances which would not be useful for early detection of AIS. With parameter sets optimized for early detection of AIS, 90% of AIS were detected with fewer than 11 target sequences, regardless of whether clustering or denoising was used. Despite developments in next-generation sequencing, sequence processing remains an important issue owing to difficulties in balancing false-positive and false-negative errors in metabarcoding data

Multiple Mechanisms Promote the Retained Expression of Gene Duplicates in the Tetraploid Frog Xenopus laevis

Gene duplication provides a window of opportunity for biological variants to persist under the protection of a co-expressed copy with similar or redundant function. Duplication catalyzes innovation (neofunctionalization), subfunction degeneration (subfunctionalization), and genetic buffering (redundancy), and the genetic survival of each paralog is triggered by mechanisms that add, compromise, or do not alter protein function. We tested the applicability of three types of mechanisms for promoting the retained expression of duplicated genes in 290 expressed paralogs of the tetraploid clawed frog, Xenopus laevis. Tests were based on explicit expectations concerning the ka/ks ratio, and the number and location of nonsynonymous substitutions after duplication. Functional constraints on the majority of paralogs are not significantly different from a singleton ortholog. However, we recover strong support that some of them have an asymmetric rate of nonsynonymous substitution: 6% match predictions of the neofunctionalization hypothesis in that (1) each paralog accumulated nonsynonymous substitutions at a significantly different rate and (2) the one that evolves faster has a higher ka/ks ratio than the other paralog and than a singleton ortholog. Fewer paralogs (3%) exhibit a complementary pattern of substitution at the protein level that is predicted by enhancement or degradation of different functional domains, and the remaining 13% have a higher average ka/ks ratio in both paralogs that is consistent with altered functional constraints, diversifying selection, or activity-reducing mutations after duplication. We estimate that these paralogs have been retained since they originated by genome duplication between 21 and 41 million years ago. Multiple mechanisms operate to promote the retained expression of duplicates in the same genome, in genes in the same functional class, over the same period of time following duplication, and sometimes in the same pair of paralogs. None of these paralogs are superfluous; degradation or enhancement of different protein subfunctions and neofunctionalization are plausible hypotheses for the retained expression of some of them. Evolution of most X. laevis paralogs, however, is consistent with retained expression via mechanisms that do not radically alter functional constraints, such as selection to preserve post-duplication stoichiometry or temporal, quantitative, or spatial subfunctionalization

T cell receptor sequence clustering and antigen specificity

There has been increasing interest in the role of T cells and their involvement in cancer, autoimmune and infectious diseases. However, the nature of T cell receptor (TCR) epitope recognition at a repertoire level is not yet fully understood. Due to technological advances a plethora of TCR sequences from a variety of disease and treatment settings has become readily available. Current efforts in TCR specificity analysis focus on identifying characteristics in immune repertoires which can explain or predict disease outcome or progression, or can be used to monitor the efficacy of disease therapy. In this context, clustering of TCRs by sequence to reflect biological similarity, and especially to reflect antigen specificity have become of paramount importance. We review the main TCR sequence clustering methods and the different similarity measures they use, and discuss their performance and possible improvement. We aim to provide guidance for non-specialists who wish to use TCR repertoire sequencing for disease tracking, patient stratification or therapy prediction, and to provide a starting point for those aiming to develop novel techniques for TCR annotation through clustering

Importin-7 mediates nuclear trafficking of DNA in mammalian cells

Eukaryotic cells have the ability to uptake and transport endogenous and exogenous DNA in their nuclei, however little is known about the specific pathways involved. Here we show that the nuclear transport receptor importin 7 (imp7) supports nuclear import of supercoiled plasmid DNA and human mitochondrial DNA in a Ran and energy-dependent way. The imp7-dependent pathway was specifically competed by excess DNA but not by excess of maltose-binding protein fused with the classical nuclear localizing signal (NLS) or the M9 peptides. Transport of DNA molecules complexed with poly-l-lysine was impaired in intact cells depleted of imp7, and DNA complexes remained localized in the cytoplasm. Poor DNA nuclear import in cells depleted of imp7 directly correlated with lower gene expression levels in these cells compared to controls. Inefficient nuclear import of transfected DNA induced greater upregulation of the interferon pathway, suggesting that rapid DNA nuclear import may prevent uncontrolled activation of the innate immune response. Our results provide evidence that imp7 is a non-redundant component of an intrinsic pathway in mammalian cells for efficient accumulation of exogenous and endogenous DNA in the nucleus, which may be critical for the exchange of genetic information between mitochondria and nuclear genomes and to control activation of the innate immune response