208 research outputs found
Growth without finance, finance without growth
The international comparative evidence on the nexus between finance and growth is ambiguous, owing to the many difficulties in isolating finance, separating its growth effect from that of the other factors. To overcome this problem, we study the effects of financial development on growth from 1960 to 2010 in one country â Italy. Thus we have the same political, legal and regulatory framework but also sharply differing development conditions between regions. After World War II Italy achieved an âeconomic miracleâ similar to what China and India are now experiencing, followed by a lengthy phase of decline. Accordingly, we can distinguish the effect of financial development on growth from other potential causal factors while also considering regions with sharply different economic conditions. Our results show that from 1960 to 1980, when the Italian âeconomic miracleâ was still under way, finance played no significant role in favouring the surge in economic growth, which most likely depended on internal consumption. Between 1980 and 2010, by contrast, the great expansion of Italian financial markets and institutions did have a positive effect on regional economic performance, but overall growth rates were nevertheless low. Although our empirical evidence supports the view that finance is more important for growth in less highly developed regions, it also shows that financial development has not helped to overcome the Italian economic divide
A chronic strain of the cystic fibrosis pathogen Pandoraeapulmonicola expresses a heterogenous hypo-acylated lipid A
Pandoraeasp. is an emerging Gram-negative pathogen in cystic fibrosis causing severe and persistent inflammation and damageof the lungs. The molecular mechanisms underlying the high pathogenicity ofPandoraeaspecies are still largely unknown. AsGram-negatives,Pandoraeasp. express lipopolysaccharides (LPS) whose recognition by the host immune system triggers aninflammatory response aimed at the bacterial eradication from the infected tissues. The degree of the inflammatory responsestrongly relies on the fine structure of the LPS and, in particular, of its glycolipid moiety, i.e. the lipid A. Here we report thestructure of the lipid A isolated from the LPS of a chronic strain ofP. pulmonicola(RL 8228), one of the most virulent identifiedso far among thePandoraeaspecies. Our data demonstrated that the examined chronic strain produces a smooth-type LPS with acomplex mixture of hypoacylated lipid A species displaying, among other uncommon characteristics, the 2-hydroxylation ofsome of the acyl chains and the substitution by an additional glucosamine on one or both the phosphate groups
The Semantics of Natural Objects and Tools in the Brain: A Combined Behavioral and MEG Study
Current literature supports the notion that the recognition of objects, when visually pre-sented, is sub-served by neural structures different from those responsible for the semantic processing of their nouns. However, embodiment foresees that processing observed objects and their verbal labels should share similar neural mechanisms. In a combined behavioral and MEG study, we com-pared the modulation of motor responses and cortical rhythms during the processing of graspable natural objects and tools, either verbally or pictorially presented. Our findings demonstrate that conveying meaning to an observed object or processing its noun similarly modulates both motor responses and cortical rhythms; being natural graspable objects and tools differently represented in the brain, they affect in a different manner both behavioral and MEG findings, independent of presentation modality. These results provide experimental evidence that neural substrates responsible for conveying meaning to objects overlap with those where the object is represented, thus supporting an embodied view of semantic processing
Technology-based Product-services for Supporting Frugal Innovation
In recent years, European manufacturing companies are gradually applying innovative PSS (Product Service Systems), as strategic opportunity for differentiating from competitors, offering an integrated bundle of products and services, targeted on specific needs of different customers. At the same time, frugal innovation has also surged as a new business concept based upon an intelligent use of resources to fulfill region-dependent customers' needs. Both approaches bring forth rethinking of established business models, which in turn asks for an in-depth analysis of the implications on the company organization and infrastructure, at supply chain and plant levels, urging towards manufacturing networks and reconfigurable assembly lines. This paper presents a formalized framework to support product-service design and the related business model characterization, in the context of frugal innovation. The methodology is applied to three real industrial scenarios respectively in the aeronautics, the domestic appliances and the machinery industry, which are analyzed within the framework of the H2020 European funded project 'ProRegio'
Lipopolysaccharide from Gut-Associated Lymphoid-Tissue-Resident Alcaligenes faecalis: Complete Structure Determination and Chemical Synthesis of Its Lipid A
Alcaligenes faecalis is the predominant Gram-negative bacterium inhabiting gut-associated lymphoid tissues, Peyer's patches. We previously reported that an A. faecalis lipopolysaccharide (LPS) acted as a weak agonist for Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD-2) receptor as well as a potent inducer of IgA without excessive inflammation, thus suggesting that A. faecalis LPS might be used as a safe adjuvant. In this study, we characterized the structure of both the lipooligosaccharide (LOS) and LPS from A. faecalis. We synthesized three lipid A molecules with different degrees of acylation by an efficient route involving the simultaneous introduction of 1- and 4â˛-phosphates. Hexaacylated A. faecalis lipid A showed moderate agonistic activity towards TLR4-mediated signaling and the ability to elicit a discrete interleukin-6 release in human cell lines and mice. It was thus found to be the active principle of the LOS/LPS and a promising vaccine adjuvant candidate
Residual dipolar coupling investigation of a heparin tetrasaccharide confirms the limited effect of flexibility of the iduronic acid on the molecular shape of heparin
The solution conformation of a fully sulfated heparin-derived tetrasaccharide, I, was studied in the presence of a 4-fold excess of Ca2+. Protonâproton and protonâcarbon residual dipolar couplings (RDCs) were measured in a neutral aligning medium. The order parameters of two rigid hexosamine rings of I were determined separately using singular value decomposition and ab initio structures of disaccharide fragments of I. The order parameters were very similar implying that a common order tensor can be used to analyze the structure of I. Using one order tensor, RDCs of both hexosamine rings were used as restraints in molecular dynamics simulations. RDCs of the inner iduronic acid were calculated for every point of the molecular dynamics trajectory. The fitting of the calculated RDCs of the two forms of the iduronic acid to the experimental values yielded a population of 1C4 and 2So conformers of iduronic acid that agreed well with the analysis based on protonâproton scalar coupling constants. The glycosidic linkage torsion angles in RDC-restrained molecular dynamics (MD) structures of I are consistent with the interglycosidic three-bond protonâcarbon coupling constants. These structures also show that the shape of heparin is not affected dramatically by the conformational flexibility of the iduronic acid ring. This is in line with conclusions of previous studies based on MD simulations and the analysis of 1H-1H NOEs. Our work therefore demonstrates the effectiveness of RDCs in the conformational analysis of glycosaminoglycans
Recent advances on smart glycoconjugate vaccines in infections and cancer
Vaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen-specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the human immunodeficiency virus or to induce cellular T-cell immunity in the fight against cancer. The recent SARS-CoV-2 outbreak has reinforced the relevance of designing smart therapeutic vaccine modalities to ensure public health. Indeed, academic and private companies have ongoing joint efforts to develop novel vaccine prototypes for this virus. Many pathogens are covered by a dense glycan-coat, which form an attractive target for vaccine development. Moreover, many tumor types are characterized by altered glycosylation profiles that are known as âtumor-associated carbohydrate antigensâ. Unfortunately, glycans do not provoke a vigorous immune response and generally serve as T-cell-independent antigens, not eliciting protective immunoglobulin G responses nor inducing immunological memory. A close and continuous crosstalk between glycochemists and glycoimmunologists is essential for the successful development of efficient immune modulators. It is clear that this is a key point for the discovery of novel approaches, which could significantly improve our understanding of the immune system. In this review, we discuss the latest advancements in development of vaccines against glycan epitopes to gain selective immune responses and to provide an overview on the role of different immunogenic constructs in improving glycovaccine efficacy
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A conserved fungal glycosyltransferase facilitates pathogenesis of plants by enabling hyphal growth on solid surfaces
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Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause diseases of plants. However, the full inventory of genes which support this is incomplete and many may be currently concealed due to their essentiality for the hyphal growth form. During a random T-DNA mutagenesis screen performed on the pleomorphic wheat (Triticum aestivum) pathogen Zymoseptoria tritici, we acquired a mutant unable to extend hyphae specifically when on solid surfaces. In contrast âyeast-likeâ growth, and all other growth forms, were unaffected. The inability to extend surface hyphae resulted in a complete loss of virulence on plants. The affected gene encoded a predicted type 2 glycosyltransferase (ZtGT2). Analysis of >800 genomes from taxonomically diverse fungi highlighted a generally widespread, but discontinuous, distribution of ZtGT2 orthologues, and a complete absence of any similar proteins in non-filamentous ascomycete yeasts. Deletion mutants of the ZtGT2 orthologue in the taxonomically un-related fungus Fusarium graminearum were also severely impaired in hyphal growth and non-pathogenic on wheat ears. ZtGT2 expression increased during filamentous growth and electron microscopy on deletion mutants (ÎZtGT2) suggested the protein functions to maintain the outermost surface of the fungal cell wall. Despite this, adhesion to leaf surfaces was unaffected in ÎZtGT2 mutants and global RNAseq-based gene expression profiling highlighted that surface-sensing and protein secretion was also largely unaffected. However, ÎZtGT2 mutants constitutively overexpressed several transmembrane and secreted proteins, including an important LysM-domain chitin-binding virulence effector, Zt3LysM. ZtGT2 likely functions in the synthesis of a currently unknown, potentially minor but widespread, extracellular or outer cell wall polysaccharide which plays a key role in facilitating many interactions between plants and fungi by enabling hyphal growth on solid matrices
Side-Payments and the Costs of Conflict
Conflict and competition often impose costs on both winners and losers, and conflicting parties may prefer to resolve the dispute before it occurs. The equilibrium of a conflict game with side-payments predicts that with binding offers, proposers make and responders accept side-payments, generating settlements that strongly favor proposers. When side-payments are non-binding, proposers offer nothing and conflicts always arise. Laboratory experiments confirm that binding side-payments reduce conflicts. However, 30 % of responders reject binding offers, and offers are more egalitarian than predicted. Surprisingly, non-binding side-payments also improve efficiency, although less than binding. With binding side-payments, 87 % of efficiency gains come from avoided conflicts. However, with non-binding side-payments, only 39 % of gains come from avoided conflicts and 61 % from reduced conflict expenditures
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