Liver transplantation

Purpose of review: Long-term survival of liver transplant recipients is threatened by increased rates of de-novo malignancy and recurrence of hepatocellular carcinoma (HCC), both events tightly related to immunosuppression. Recent findings: There is accumulating evidence linking increased exposure to immunosuppressants and carcinogenesis, particularly concerning calcineurin inhibitors (CNIs), azathioprine and antilymphocyte agents. A recent study including 219 HCC transplanted patients showed that HCC recurrence rates were halved if a minimization of CNIs was applied within the first month after liver transplant. With mammalian target of rapamycin (mTOR) inhibitors as approved immunosuppressants for liver transplant patients, pooled data from several retrospective studies have suggested their possible benefit for reducing HCC recurrence. Summary: Randomized controlled trials with sufficiently long follow-up are needed to evaluate the influence of different immunosuppression protocols in preventing malignancy after LT. Currently, early minimization of CNIs with or without mTOR inhibitors or mycophenolate seems a rational strategy for patients with risk factors for de-novo malignancy or recurrence of HCC after liver transplant. A deeper understanding of the immunological pathways of rejection and cancer would allow for designing more specific and safer drugs, and thus to prevent cancer after liver transplant

Junctional sarcoplasmic reticulum motility in adult mouse ventricular myocytes.

Excitation-contraction (EC) coupling is the coordinated process by which an action potential triggers cardiac myocyte contraction. EC coupling is initiated in dyads where the junctional sarcoplasmic reticulum (jSR) is in tight proximity to the sarcolemma of cardiac myocytes. Existing models of EC coupling critically depend on dyad stability to ensure the fidelity and strength of EC coupling, where even small variations in ryanodine receptor channel and voltage-gated calcium channel-α 1.2 subunit separation dramatically alter EC coupling. However, dyadic motility has never been studied. Here, we developed a novel strategy to track specific jSR units in dissociated adult ventricular myocytes using photoactivatable fluorescent proteins. We found that the jSR is not static. Instead, we observed dynamic formation and dissolution of multiple dyadic junctions regulated by the microtubule-associated molecular motors kinesin-1 and dynein. Our data support a model where reproducibility of EC coupling results from the activation of a temporally averaged number of SR Ca2+ release units forming and dissolving SR-sarcolemmal junctions. These findings challenge the long-held view that the jSR is an immobile structure and provide insights into the mechanisms underlying its motility

Evaluation of CNN architectures for gait recognition based on optical flow maps

This work targets people identification in video based on the way they walk (\ie gait) by using deep learning architectures. We explore the use of convolutional neural networks (CNN) for learning high-level descriptors from low-level motion features (\ie optical flow components). The low number of training samples for each subject and the use of a test set containing subjects different from the training ones makes the search of a good CNN architecture a challenging task.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Microstructural Characterization of Silver Nanoparticles for Bioimaging Applications

Junta de Andalucía FQM-6615, PI0070, FQM31

Sulfonate-terminated carbosilane dendron-coated nanotubes: a greener point of view in protein sample preparation

Reduction or removal of solvents and reagents in protein sample preparation is a requirement. Dendrimers can strongly interact with proteins and have great potential as a greener alternative to conventional methods used in protein sample preparation. This work proposes the use of single-walled carbon nanotubes (SWCNTs) functionalized with carbosilane dendrons with sulfonate groups for protein sample preparation and shows the successful application of the proposed methodology to extract proteins from a complex matrix. SEM images of nanotubes and mixtures of nanotubes and proteins were taken. Moreover, intrinsic fluorescence intensity of proteins was monitored to observe the most significant interactions at increasing dendron generations under neutral and basic pHs. Different conditions for the disruption of interactions between proteins and nanotubes after protein extraction and different concentrations of the disrupting reagent and the nanotube were also tried. Compatibility of extraction and disrupting conditions with the enzymatic digestion of proteins for obtaining bioactive peptides was also studied. Finally, sulfonate-terminated carbosilane dendron-coated SWCNTs enabled the extraction of proteins from a complex sample without using non-environmentally friendly solvents that were required so far

Ruthenium metallodendrimer against triple-negative breast cancer in mice

Carbosilane metallodendrimers, based on the arene Ru(II) complex (CRD13) and integrated to imino-pyridine surface groups have been investigated as an anticancer agent in a mouse model with triple-negative breast cancer. The dendrimer entered into the cells efficiently, and exhibited selective toxicity for 4T1 cells. In vivo investigations proved that a local injection of CRD13 caused a reduction of tumour mass and was non-toxic. ICP analyses indicated that Ru(II) accumulated in all tested tissues with a greater content detected in the tumour.European CommissionMinisterio de Economía y CompetitividadComunidad de MadridJunta de Comunidades de Castilla-La Manch

Factors affecting interactions between sulphonate-terminated dendrimers and proteins: A three case study

This work proposes a deep study on the interactions between sulphonate-terminated carbosilane dendrimers and proteins. Three different proteins with different molecular weights and isoelectric points were employed and different pHs, dendrimer concentrations and generations were tested. Variations in fluorescence intensity and emission wavelength were used as protein-dendrimer interaction probes. Interaction between dendrimers and proteins greatly depended on the protein itself and pH. Other important issues were the dendrimer concentration and generation. Protein-dendrimer interactions were favored under acidic working conditions when proteins were positively charged. Moreover, in general, high dendrimer generations promoted these interactions. Modeling of protein-dendrimer interactions allowed to understand the different behaviors observed for every protein. (C) 2016 Elsevier B.V. All rights reserved

Study of non-covalent interactions on dendriplex formation: Influence of hydrophobic, electrostatic and hydrogen bonds interactions

The interaction of a double stranded small interference RNA (siRNA Nef) with cationic carbosilane dendrimers of generations 1-3 with two different ammonium functions at the periphery ([-NMe2R](+), R=Me, (CH2)(2)OH) has been studied by experimental techniques (zeta potential, electrophoresis, single molecule pulling experiments) and molecular dynamic calculations. These studies state the presence of different forces on dendriplex formation, depending on generation and type of ammonium group. Whilst for higher dendrimers electrostatic forces mainly drive the stability of dendriplexes, first generation compounds can penetrate into siRNA strands due to the establishment of hydrophobic interactions. Finally, in the particular case of first generation dendrimer [G(1)O(3)(NMe2(CH2)(2)OH))(6)](6+); the presence of hydroxyl groups reinforces dendriplex stability by hydrogen bonds formation. However, since these small dendrimers do not cover the RNA, only higher generation derivatives protect RNA from degradation.University of Alcalá; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN); Instituto de Investigación Sanitaria Gregorio Marañón; Universitat de Barcelon

Integration over the space of functions and Poincar´e series: a revision

Producción CientíficaEarlier (2000) the authors introduced the notion of the integral with respect to the Euler characteristic over the space of germs of functions on a variety and over its projectivization. This notion permitted to rewrite in new terms known definitions and statements and also appeared to be an effective tool to compute Poincar´e series of multi-index filtrations in some situations. However the “classical” (initial) notion can be applied only to multi-index filtrations defined by so-called finitely determined valuations (or order functions). Here we introduce a modified version of the notion of the integral with respect to the Euler characteristic over the projectivization of the space of function germs. This version can be applied in a number of settings where the “classical approach” does not work. We give examples of application of this concept for definitions and computations of the Poincar´e series of collections of plane valuations which include valuations not centred at the origin, including equivariant ones.Ministerio de Economía, Industria y Competitividad (MTM2015-65764-C3-1-P)Russian Science Foundation (grant 16-11- 10018

Equivariant Poincaré series and topology of valuations

The equivariant with respect to a finite group action Poincaré series of a collection of r valuations was defined earlier as a power series in r variables with the coefficients from a modification of the Burnside ring of the group. Here we show that (modulo simple exceptions) the equivariant Poincar ́e series determines the equivariant topology of the collection of valuations.Supported by the grants MTM2012-36917-C03-01 / 02 and MTM2015-65764-C3-1- P (first grant with the help of FEDER Program