Observational constraints to boxy/peanut bulge formation time

Boxy/peanut bulges are considered to be part of the same stellar structure as bars and both could be linked through the buckling instability. The Milky Way is our closest example. The goal of this letter is determining if the mass assembly of the different components leaves an imprint in their stellar populations allowing to estimate the time of bar formation and its evolution. To this aim we use integral field spectroscopy to derive the stellar age distributions, SADs, along the bar and disc of NGC 6032. The analysis shows clearly different SADs for the different bar areas. There is an underlying old (>=12 Gyr) stellar population for the whole galaxy. The bulge shows star formation happening at all times. The inner bar structure shows stars of ages older than 6 Gyrs with a deficit of younger populations. The outer bar region presents a SAD similar to that of the disc. To interpret our results, we use a generic numerical simulation of a barred galaxy. Thus, we constrain, for the first time, the epoch of bar formation, the buckling instability period and the posterior growth from disc material. We establish that the bar of NGC 6032 is old, formed around 10 Gyr ago while the buckling phase possibly happened around 8 Gyr ago. All these results point towards bars being long-lasting even in the presence of gas.Comment: Accepted for publication in MNRAS Letter

Preparation of Dipteran Larvae for Scanning Electron Microscopy with Special Reference to Myiasigen Dipteran Species

Although controversy exists concerning the role of chemical fixatives in scanning electron microscopy (SEM) studies of Dipteran larvae, we have observed that filtered 10% formaldehyde solution gives excellent results as a preservative. After immersing in vivo in formaldehyde, the larvae material is preserved for prolonged periods (up to 8 months), before examination with SEM. As a fixative, formaldehyde preserves the structure of the larval cuticle and produces no visible artifacts. Moreover, postfixation is not necessary. Due to pecularities of the way of life of Wohlfahrtia magnifica (principally the accumulations of necrotic tissue, purulent particles, and other types of substances that often adhere to the numerous spines of larvae), this species must be cleaned before examination by SEM. Manual cleaning with alternating bidistilled water and 0.9% saline solution proved to be a rapid, easy and inexpensive method that gave good results. Both lyophilization drying and critical point drying were used before sputtering the material. While lyophilization drying proved to be the most effective method for instars II and III, critical point drying was the best technique for study of specimens belonging to instar I. The optimum time for drying and conditions for lyophilization and sputter-coating with gold were determined experimentally. Samples were mounted on SEM stubs with double-sided adhesive and silver conductive paint. The method proposed is easy and effective for the SEM study of larvae myiasis-producing diptera

Dendrimers-modified solid supports: towards nanostructures materials for clinical diagnostic

Conferencia Invitada al XXXIV Reunion Bienal de la Real Sociedad Española de Quimica. Santander, 2013The design and synthesis of new materials for biomedical applications is a high-priority research topic in a number of biomedical areas. The rapid development of nanotechnology over the past few decades has created wide prospects for using nano- and micro-scale materials in such areas, where careful control of interactions between particles and biosystems is essential for effective use of these materials in biomedicine. Worth special note in this respect is the use of nanoparticles in diagnostic assays, where chemists are playing an increasingly role in designing and producing new materials for manufacturing sensors affording increased sensitivity and selectivity relative to conventional diagnostic systems. The three-dimensional architecture of dendrimeric systems confers them some intrinsic features such as structural homogeneity, integrity, controlled composition and high-density multidentate homogeneous ends ready for (bio)conjugation. These properties make dendrimeric systems unique and stable enough for a variety of applications. This has boosted the use of dendrimers for biosensing purposes in recent years. We describe here recent progress in the preparation of new materials for biosensor applications. Specifically, we report on the use of zeolites and silica particles as a solid support for RadioAllergoSorbent Test (RAST) with a view to its use as a complementary diagnostic method for identifying allergic responses to drugs. To this end, we prepared nanoconjugated Dendrimeric Antigens (DeAn) peripherally decorated with the suspected amoxicillin hapten. Zeolites and Silica particles were modified with these novel synthetic Dendrimeric Antigens to obtain DeAn@Zeolite or SiO2NP which constitutes an effective, innovative nano system for biosensing

Methionine adenosyltransferase S-nitrosylation is regulated by the basic and acidic amino acids surrounding the target thiol

S-Adenosylmethionine serves as the methyl donor for many biological methylation reactions and provides the propylamine group for the synthesis of polyamines. S-Adenosylmethionine is synthesized from methionine and ATP by the enzyme methionine adenosyltransferase. The cellular factors regulating S-adenosylmethionine synthesis have not been well defined. Here we show that in rat hepatocytes S-nitrosoglutathione monoethyl ester, a cell-permeable nitric oxide donor, markedly reduces cellular S-adenosylmethionine content via inactivation of methionine adenosyltransferase by S-nitrosylation. Removal of the nitric oxide donor from the incubation medium leads to the denitrosylation and reactivation of methionine adenosyltransferase and to the rapid recovery of cellular S-adenosylmethionine levels. Nitric oxide inactivates methionine adenosyltransferase via S-nitrosylation of cysteine 121. Replacement of the acidic (aspartate 355) or basic (arginine 357 and arginine 363) amino acids located in the vicinity of cysteine 121 by serine leads to a marked reduction in the ability of nitric oxide to S-nitrosylate and inactivate hepatic methionine adenosyltransferase. These results indicate that protein S-nitrosylation is regulated by the basic and acidic amino acids surrounding the target cysteine

Impact of prophylactic TNF blockade in the dual PD-1 and CTLA-4 immunotherapy efficacy and toxicity

The TNF blockade therapy is currently a well-established treatment option for a variety of autoimmune diseases such as rheumatoid arthritis (RA), psoriasis or Crohn's disease, given the proinflammatory role of TNF in the course of these diseases. Importantly, TNF neutralization is also used for the treatment of corticosteroid-refractory immune-related adverse events (irAEs) induced by the combined anti-PD-1 and anti-CTLA-4 immunotherapy. The manifestation of these toxicities is an important limiting factor for the successful implementation of the inhibitory checkpoint blockade therapy (ICB), restraining its anti-tumor efficacy. In our recent study (Perez-Ruiz et al., Nature 569(7756): 428-432.), we analyzed the potential impact of prophylactic TNF neutralization therapy in the anti-PD1/CTLA-4 efficacy. Through several mouse models, we demonstrated that TNF neutralization ameliorated ICB-exacerbated colitis in addition to improving ICB-dependent anti-tumor efficacy. Similar results were obtained after prophylactic TNF blockade in graft vs host xenografted mouse models with human immune cells, which showed a reduction in colitis and hepatitis. Importantly, there was a preservation of the immunotherapeutic control of xenografted tumors after ICB treatment. Moreover, TNF and TNF-dependent gene expression is upregulated in the colon mucosa from patients affected by colitis as a side effect of ipilimumab and nivolumab. Our results, thus, provide evidence of the successful combination of prophylactic TNF neutralization with ICB therapy strategy to ameliorate toxicities, while keeping or even ameliorating anti-tumor efficacy. The prophylactic TNF blockade strategy is clinically feasible since excellent TNF inhibitors have been approved for the treatment of autoimmunity and are used for the immune-related serious adverse events in immunotherapy

Analysis of Li-ion battery degradation using self-organizing maps

This paper proposes a new methodology to identify the different degradation processes of Li-Ion battery cells. The goal of this study is to determine if different degradation factors can be separated by waveform analysis from aged cells with similar remaining capacity. In contrast to other works, the proposed method identifies the past operating conditions in the cell, regardless of the actual State of Health. The methodology is based on a data-driven approach by using a SOM (Self-organizing map), an unsupervised neural network. To verify the hypothesis a SOM has been trained with laboratory data from whole data cycles, to classify cells concerning their degradation path and according to their discharge voltage patterns. Additionally, this new methodology based on the SOM allows discriminating groups of cells with different cycling conditions (based on depth of discharge, ambient temperature and discharge current). This research line is very promising for classification of used cells, not only depending on their current static parameters (capacity, impedance), but also the battery use in their past life. This will allow making predictions of the Remaining Useful Life (RUL) of a battery with greater precision

Observation of a topologically protected state in a magnetic domain wall stabilized by a ferromagnetic chemical barrier

The precise control and stabilization of magnetic domain walls is key for the development of the next generation magnetic nano-devices. Among the multitude of magnetic configurations of a magnetic domain wall, topologically protected states are of particular interest due to their intrinsic stability. In this work, using XMCD-PEEM, we have observed a topologically protected magnetic domain wall in a ferromagnetic cylindrical nanowire. Its structure is stabilized by periodic sharp alterations of the chemical composition in the nanowire. The large stability of this topologically protected domain wall contrasts with the mobility of other non-protected and non-chiral states also present in the same nanowire. The micromagnetic simulations show the structure and the conditions required to find the topologically protected state. These results are relevant for the design of future spintronic devices such as domain wall based RF oscillators or magnetic memories

Genetic heterogeneity in the toxicity to systemic adenoviral gene transfer of interleukin-12

Despite the efficacy of IL-12 in cancer experimental models, clinical trials with systemic recombinant IL-12 showed unacceptable toxicity related to endogenous IFNgamma production. We report that systemic administration of a recombinant adenovirus encoding IL-12 (AdCMVmIL-12) has a dramatically different survival outcome in a number of mouse pure strains over a wide range of doses. For instance at 2.5 x 10(9) p.f.u., systemic AdCMVmIL-12 killed all C57BL/6 mice but spared all BALB/c mice. Much higher IFNgamma concentrations in serum samples of C57BL/6 than in those from identically treated BALB/c were found. Causes for heterogeneous toxicity can be traced to differences among murine strains in the levels of gene transduction achieved in the liver, as assessed with adenovirus coding for reporter genes. In accordance, IL-12 serum concentrations are higher in susceptible mice. In addition, sera from C57BL/6 mice treated with AdCMVmIL-12 showed higher levels of IL-18, a well-known IFNgamma inducer. Interestingly, lethal toxicity in C57BL/6 mice was abolished by administration of blocking anti-IFNgamma mAbs and also by simultaneous depletion of T cells, NK cells, and macrophages. These observations together with the great dispersion of IFNgamma produced by human PBMCs upon in vitro stimulation with IL-12, or infection with recombinant adenovirus encoding IL-12, suggest that patients might also show heterogeneous degrees of toxicity in response to IL-12 gene transfer