Fluctuations and Instabilities of Ferromagnetic Domain Wall pairs in an External Magnetic Field

Soliton excitations and their stability in anisotropic quasi-1D ferromagnets are analyzed analytically. In the presence of an external magnetic field, the lowest lying topological excitations are shown to be either soliton-soliton or soliton-antisoliton pairs. In ferromagnetic samples of macro- or mesoscopic size, these configurations correspond to twisted or untwisted pairs of Bloch walls. It is shown that the fluctuations around these configurations are governed by the same set of operators. The soliton-antisoliton pair has exactly one unstable mode and thus represents a critical nucleus for thermally activated magnetization reversal in effectively one-dimensional systems. The soliton-soliton pair is stable for small external fields but becomes unstable for large magnetic fields. From the detailed expression of this instability threshold and an analysis of nonlocal demagnetizing effects it is shown that the relative chirality of domain walls can be detected experimentally in thin ferromagnetic films. The static properties of the present model are equivalent to those of a nonlinear sigma-model with anisotropies. In the limit of large hard-axis anisotropy the model reduces to a double sine-Gordon model.Comment: 15 pages RevTex 3.0 (twocolumn), 9 figures available on request, to appear in Phys Rev B, Dec (1994

Exercising a firm’s growth options: A portfolio approach

Producción CientíficaThis paper investigates a firm’s decision to exercise its growth options within the current scope of business. We contend that the point at which a firm chooses whether or not to exercise such options depends on several strategic characteristics associated to its portfolio of businesses (i.e. level of diversification, average volatility of its current business, relatedness among them, and rivalry in its core business). Using a sample of U.S. companies from 1998 to 2013, we find evidence that a firm’s level of diversification and the volatility of its current business deter immediate growth option exercise. In contrast, relatedness and rivalry in its core business trigger growth options exercise. Our portfolio perspective differs from the bulk of the literature on real options, which evaluates each growth option exercise in isolation, and contributes to furthering knowledge on the drivers underlying a diversified firm's strategic investments.Junta de Castilla y León (grant VA260U14)Gobierno de la Comunidad de Madrid - Fondo Social Europeo (grant EARLYFIN, S2015/HUM-3353)Ministerio de Ciencia e Innovación (grants ECO2017-84864-P and ECO2017-85356-P

The ectodomains of the lymphocyte scavenger receptors CD5 and CD6 interact with tegumental antigens from Echinococcus granulosus sensu lato and protect mice against secondary cystic echinococcosis

Background: Scavenger Receptors (SRs) from the host's innate immune system are known to bind multiple ligands to promote the removal of non-self or altered-self targets. CD5 and CD6 are two highly homologous class I SRs mainly expressed on all T cells and the B1a cell subset, and involved in the fine tuning of activation and differentiation signals delivered by the antigen-specific receptors (TCR and BCR, respectively), to which they physically associate. Additionally, CD5 and CD6 have been shown to interact with and sense the presence of conserved pathogen-associated structures from bacteria, fungi and/or viruses. Methodology/Principal findings: We report herein the interaction of CD5 and CD6 lymphocyte surface receptors with Echinococcus granulosus sensu lato (s.l.). Binding studies show that both soluble and membrane-bound forms of CD5 and CD6 bind to intact viable protoscoleces from E. granulosus s.l. through recognition of metaperiodate-resistant tegumental components. Proteomic analyses allowed identification of thioredoxin peroxidase for CD5, and peptidyl-prolyl cis-trans isomerase (cyclophilin) and endophilin B1 (antigen P-29) for CD6, as their potential interactors. Further in vitro assays demonstrate that membrane-bound or soluble CD5 and CD6 forms differentially modulate the pro- and anti-inflammatory cytokine release induced following peritoneal cells exposure to E. granulosus s.l. tegumental components. Importantly, prophylactic infusion of soluble CD5 or CD6 significantly ameliorated the infection outcome in the mouse model of secondary cystic echinococcosis. Conclusions/Significance Taken together, the results expand the pathogen binding properties of CD5 and CD6 and provide novel evidence for their therapeutic potential in human cystic echinococcosis. Author summary: Scavenger Receptors (SRs) are constituents of host's innate immune system able to sense and remove altered-self and/or pathogen components. Data on their interaction with helminth parasites is scarce. In this work, we describe that CD5 and CD6 -two lymphoid SRs previously reported to interact with conserved structures from bacteria, fungi and viruses- recognize tegumental components in the cestode parasite Echinococcus granulosus sensu lato (s.l.). Moreover, both receptors differentially modulate the cytokine release by host cells exposed to E. granulosus s.l. tegumental components. Importantly, the infusion of soluble forms of CD5 or CD6 improve infection outcomes in a murine model of secondary cystic echinococcosis. In summary, our results expand the pathogen binding properties of CD5 and CD6 and suggest their therapeutic potential against helminth infections

A C˄S-cyclometallated gold(III) complex as novel antibacterial candidate against drug-resistant bacteria

The worldwide emergence and spread of infections caused by multidrug-resistant bacteria endangers the efficacy of current antibiotics in the clinical setting. The lack of new antibiotics in the pipeline points to the need of developing new strategies. Recently, gold-based drugs are being repurposed for antibacterial applications. Among them, gold(III) complexes have received increasing attention as metal-based anticancer agents. However, reports on their antibacterial activity are scarce due to stability issues. The present work demonstrates the antibacterial activity of the gold(III) complex 2 stabilized as C∧S-cycloaurated containing a diphenylphosphinothioic amide moiety, showing minimum inhibitory concentration (MIC) values that ranged from 4 to 8 and from 16 to 32 mg/L among Gram-positive and Gram-negative multidrug-resistant (MDR) pathogens, respectively. Complex 2 has a biofilm inhibitory activity of only two to four times than its MIC. We also describe for the first time a potent antibacterial synergistic effect of a gold(III) complex combined with colistin, showing a bactericidal effect in less than 2 h; confirming the role of the outer membrane as a permeability barrier. Complex 2 shows a low rate of internalization in Staphylococcus aureus and Acinetobacter baumannii; it does not interact with replication enzymes or efflux pumps, causes ultrastructural damages in both membrane and cytoplasmic levels, and permeabilizes the bacterial membrane. Unlike control antibiotics, complex 2 did not generate resistant mutants in 30-day sequential cultures. We detected lower cytotoxicity in a non-tumoral THLE-2 cell line (IC50 = 25.5 μM) and no acute toxicity signs in vivo after an i.v. 1-mg/kg dose. The characterization presented here reassures the potential of complex 2 as a new chemical class of antimicrobial agents

Conserved bacterial-binding peptides of the scavenger-like lymphocyte receptor CD6 protect from mouse experimental sepsis

Sepsis is an unmet clinical need constituting one of the most important causes of death worldwide, a fact aggravated by the appearance of multidrug resistant strains due to indiscriminate use of antibiotics. Host innate immune receptors involved in pathogen-associated molecular patterns (PAMPs) recognition represent a source of broad-spectrum therapies alternative or adjunctive to antibiotics. Among the few members of the ancient and highly conserved scavenger receptor cysteine-rich superfamily (SRCR-SF) sharing bacterial-binding properties there is CD6, a lymphocyte-specific surface receptor. Here, we analyze the bacterial-binding properties of three conserved short peptides (11-mer) mapping at extracellular SRCR domains of human CD6 (CD6.PD1, GTVEVRLEASW; CD6.PD2 GRVEMLEHGEW; and CD6.PD3, GQVEVHFRGVW). All peptides show high binding affinity for PAMPs from Gram-negative (lipopolysaccharide; Kd from 3.5 to 3,000 nM) and Gram-positive (lipoteichoic acid; Kd from 36 to 680 nM) bacteria. The CD6.PD3 peptide possesses broad bacterial-agglutination properties and improved survival of mice undergoing polymicrobial sepsis in a dose- and time-dependent manner. Accordingly, CD6.PD3 triggers a decrease in serum levels of both pro-inflammatory cytokines and bacterial load. Interestingly, CD6.PD3 shows additive survival effects on septic mice when combined with Imipenem/Cilastatin. These results illustrate the therapeutic potential of peptides retaining the bacterial-binding properties of native CD6

Screening for Trypanosoma cruzi infection in immigrants and refugees: Systematic review and recommendations from the Spanish Society of Infectious Diseases and Clinical Microbiology

BackgroundChagas disease has spread beyond its original borders on the American continent with migration. It can be transmitted from mother to child, through organ transplantation and transfusion of blood and blood products. It is necessary to determine when to screen for this infection.AimOur objective was to evaluate the appropriateness of screening for Trypanosoma cruzi infection in Latin American migrants and their descendants.MethodsWe reviewed the literature using rigorous criteria. The quality of evidence was ranked according to the GRADE classification. An evidence to decision framework was adopted to provide information on the most relevant aspects necessary to formulate recommendations.ResultsThe 33 studies evaluated revealed a prevalence of T. cruzi infection among Latin American migrants in Europe of 6.08% (95% confidence interval (CI): 3.24-9.69; 28 studies). Vertical transmission occurred in three of 100 live births (95% CI: 1-6; 13 studies). The prevalence of cardiovascular disease was 19% (95% CI: 13-27; nine studies), including only 1% severe cardiac events (95% CI: 0-2; 11 studies). The overall quality of evidence was low because of risk of bias in the studies and considerable heterogeneity of the evaluated populations. The recommendations took into account economic studies on the value of screening strategies and studies on acceptability of screening and knowledge of the disease in the affected population.ConclusionsWe identified five situations in which screening for T. cruzi infection is indicated. We recommend screening persons from endemic areas and children of mothers from these areas

Novel tumor-targeted self-nanostructured and compartmentalized water-in-oil-in-water polyurethane-polyurea nanocapsules for cancer theragnosis

Encapsulation of water-soluble bioactive compounds for enabling specific accumulation in tumor locations, while avoiding premature clearance and/or degradation in the bloodstream, is one of the main hallmarks in nanomedicine, especially that of NIR fluorescent probes for cancer theragnosis. The herein reported technology furnishes water-dispersible double-walled polyurethane-polyurea hybrid nanocapsules (NCs) loaded with indocyanine green (ICG-NCs), using a versatile and highly efficient one-pot and industrially scalable synthetic process based on the use of two different prepolymers to set up the NCs walls. Flow cytometry and confocal microscopy confirmed that both ICG-loaded NCs internalized in monocyte-derived dendritic cells (moDCs). The in vivo analysis of xenograft A375 mouse melanoma model revealed that amphoteric functionalization of NCs' surface promotes the selective accumulation of ICG-NCs in tumor tissues, making them promising agents for a less-invasive theragnosis of cancer

CD6 deficiency impairs early immune response to bacterial sepsis

CD6 is a lymphocyte-specific scavenger receptor expressed on adaptive (T) and innate (B1a, NK) immune cells, which is involved in both fine-tuning of lymphocyte activation/differentiation and recognition of bacterial-associated molecular patterns (i.e., lipopolysaccharide). However, evidence on CD6's role in the physiological response to bacterial infection was missing. Our results show that induction of monobacterial and polymicrobial sepsis in Cd6 -/- mice results in lower survival rates and increased bacterial loads and pro-inflammatory cytokine levels. Steady state analyses of Cd6 -/- mice show decreased levels of natural polyreactive antibodies, concomitant with decreased cell counts of spleen B1a and marginal zone B cells. Adoptive transfer of wild-type B cells and mouse serum, as well as a polyreactive monoclonal antibody improve Cd6 -/- mouse survival rates post-sepsis. These findings support a nonredundant role for CD6 in the early response against bacterial infection, through homeostatic expansion and functionality of innate-related immune cells

Extracellular NK histones promote immune cell anti-tumor activity by inducing cell clusters through binding to CD138 receptor.

BACKGROUND: Natural killer (NK) cells are important anti-tumor cells of our innate immune system. Their anti-cancer activity is mediated through interaction of a wide array of activating and inhibitory receptors with their ligands on tumor cells. After activation, NK cells also secrete a variety of pro-inflammatory molecules that contribute to the final immune response by modulating other innate and adaptive immune cells. In this regard, external proteins from NK cell secretome and the mechanisms by which they mediate these responses are poorly defined. METHODS: TRANS-stable-isotope labeling of amino acids in cell culture (TRANS-SILAC) combined with proteomic was undertaken to identify early materials transferred between cord blood-derived NK cells (CB-NK) and multiple myeloma (MM) cells. Further in vitro and in vivo studies with knock-down of histones and CD138, overexpression of histones and addition of exogenous histones were undertaken to confirm TRANS-SILAC results and to determine functional roles of this material transferred. RESULTS: We describe a novel mechanism by which histones are actively released by NK cells early after contact with MM cells. We show that extracellular histones bind to the heparan sulfate proteoglycan CD138 on the surface of MM cells to promote the creation of immune-tumor cell clusters bringing immune and MM cells into close proximity, and thus facilitating not only NK but also T lymphocyte anti-MM activity. CONCLUSION: This study demonstrates a novel immunoregulatory role of NK cells against MM cells mediated by histones, and an additional role of NK cells modulating T lymphocytes activity that will open up new avenues to design future immunotherapy clinical strategies