Optical micro-elastography with magnetic excitation for high frequency rheological characterization of soft media

The propagation of shear waves in elastography at high frequency (>3 kHz) in viscoelastic media has not been extensively studied due to the high attenuation and technical limitations of current techniques. An optical micro-elastography (OME) technique using magnetic excitation for generating and tracking high frequency shear waves with enough spatial and temporal resolution was proposed. Ultrasonics shear waves (above 20 kHz) were generated and observed in polyacrylamide samples. A cutoff frequency, from where the waves no longer propagate, was observed to vary depending on the mechanical properties of the samples. The ability of the Kelvin–Voigt (KV) model to explain the high cutoff frequency was investigated. Two alternative measurement techniques, Dynamic Mechanical Analysis (DMA) and Shear Wave Elastography (SWE), were used to complete the whole frequency range of the velocity dispersion curve while avoid capturing guided waves in the low frequency range (<3 kHz). The combination of the three measurement techniques provided rheology information from quasi-static to ultrasonic frequency range. A key observation was that the full frequency range of the dispersion curve was necessary if one wanted to infer accurate physical parameters from the rheological model. By comparing the low frequency range with the high frequency range, the relative errors for the viscosity parameter could reach 60 % and they could be higher with higher dispersive behavior. The high cutoff frequency may be predicted in materials that follow a KV model over their entire measurable frequency range. The mechanical characterization of cell culture media could benefit from the proposed OME technique.Ministerio de Educación, Cultura y Deporte, Spain grant numbers DPI2017-83859-R, and EQC2018- 004508-PMinisterio de Ciencia e Innovación, Spain grant numbers PID2020-115372RB-I00, PYC20 RE 072 UGRMinisterio de Sanidad, Servicios Sociales e Igualdad, Spain grant numbers DTS15/00093PI16/00339; Instituto de Salud Carlos IIIFondos Feder, Spain; Junta de AndalucíaSpain grant numbers PI-0107-2017PIN-0030-2017IE2017-5537; P21-00182Consejería de Universidad, Investigación e Innovación de la Junta de AndalucíaMCIN/AEI 10.13039/501100011 033 grant number PRE2018-086085 (Co-funded by European Social Fund ‘‘Investing in your future’’)European Regional Development Fund (ERDF) SOMM17/6109/UGRB-TEP-026IE2017-5537P18-RT- 165

Rotavirus and autoimmunity

Rotavirus, a major etiological agent of acute diarrhea in children worldwide, has historically been linked to autoimmunity. In the last few years, several physiopathological approaches have been proposed to explain the leading mechanism triggering autoimmunity, from the old concept of molecular mimicry to the emerging theory of bystander activation and break of tolerance. Epidemiological and immunological data indicate a strong link between rotavirus infection and two of the autoimmune pathologies with the highest incidence: celiac disease and diabetes. The role for current oral rotavirus vaccines is now being elucidated, with a so far positive protective association demonstrated

MAX mutant small-cell lung cancers exhibit impaired activities of MGA-dependent noncanonical polycomb repressive complex

The MYC axis is disrupted in cancer, predominantly through activation of the MYC family oncogenes but also through inactivation of the MYC partner MAX or of the MAX partner MGA. MGA and MAX are also members of the polycomb repressive complex, ncPRC1.6. Here, we use genetically modified MAX-deficient small-cell lung cancer (SCLC) cells and carry out genome-wide and proteomics analyses to study the tumor suppressor function of MAX. We find that MAX mutant SCLCs have ASCL1 or NEUROD1 or combined ASCL1/NEUROD1 characteristics and lack MYC transcriptional activity. MAX restitution triggers prodifferentiation expression profiles that shift when MAX and oncogenic MYC are coexpressed. Although ncPRC1.6 can be formed, the lack of MAX restricts global MGA occupancy, selectively driving its recruitment toward E2F6-binding motifs. Conversely, MAX restitution enhances MGA occupancy to repress genes involved in different functions, including stem cell and DNA repair/replication. Collectively, these findings reveal that MAX mutant SCLCs have either ASCL1 or NEUROD1 or combined characteristics and are MYC independent and exhibit deficient ncPRC1.6-mediated gene repression.We thank Isabel Bartolessis for technical assistance, the confocal facility (Carmen Casals) and the RNA-sequencing genomic facility (Anna Esteve) for important services. Funding: This work was supported by Spanish grant SAF2017-82186-RAEI/FEDER (UE) (to MSC) from the MINECO and a grant from the Fundación Científica Asociación Española Contra el Cancer- GCB14142170MONT (to MSC). M Torres-Diz was supported by the FPI-fellowship: BES- 2012-054579, P Llabata by the FPI-fellowship: BES-2015-072204 and by the European Association for Cancer Research Travel fellowship and L Tomas-Daza by the FPI-fellowship (number PRE2019-088005). BMJ is funded by Spanish Ministry of Science, Innovation, and Universities (MICINN) project number RTI2018-094788-A-I00 and by La Caixa Banking Foundation Junior Leader project (LCF/BQ/PI19/11690001). The proteomics analyses were performed in the IJC Proteomics Unit. The IJC Proteomics Unit is part of the Spanish Platform of Molecular and Bioinformatics Resources (ProteoRed), Instituto de Salud Carlos III (PT13/0001). Competing Interests: All authors declare no competing financial interests.Peer Reviewed"Article signat per 12 autors/es: Paula Llabata, Manuel Torres-Diz, Antonio Gomez, Laureano Tomas-Daza, Octavio A. Romero, Joaquim Grego-Bessa, Pere Llinas-Arias, Alfonso Valencia, Manel Esteller, Biola M. Javierre, Xiaoyang Zhang, and Montse Sanchez-Cespedes"Postprint (author's final draft

Ether gas-sensor based on Au nanoparticles-decorated ZnO microstructures

Trabajo de Investigación derivado de la estancia Posdoctoral del Dr. Roberto LópezAn ether gas-sensor was fabricated based on gold nanoparticles (Au-NPs) decorated zinc oxide microstructures (ZnO-MS). Scanning electron microscope (SEM) and high-resolution transmission elec- tron microscope (HRTEM) measurements were performed to study morphological and structural proper- ties, respectively, of the ZnO-MS. The gas sensing response was evaluated in a relatively low temperature regime, which ranged between 150 and 250 C. Compared with a sensor fabricated from pure ZnO-MS, the sensor based on Au-NPs decorated ZnO-MS showed much better ether gas response at the highest working temperature. In fact, pure ZnO-MS based sensor only showed a weak sensitivity of about 25%. The improvement of the ether gas response for sensor fabricated with Au-NPs decorated ZnO-MS was attributed to the catalytic activity of the Au-NPs.Investigación realizada bajo proyecto UAEM 1025/2014RIF

Bulk viscosity of low-temperature strongly interacting matter

We study the bulk viscosity of a pion gas in unitarized Chiral Perturbation Theory at low and moderate temperatures, below any phase transition to a quark-gluon plasma phase. We argue that inelastic processes are irrelevant and exponentially suppressed at low temperatures. Since the system falls out of chemical equilibrium upon expansion,a pion chemical potential must be introduced, so we extend the existing theory to include it. We control the zero modes of the collision operator and Landau's conditions of fit when solving the Boltzmann equation with the elastic collision kernel. The dependence of the bulk viscosity with temperature is reminiscent of the findings of Fernandez-Fraile and Gomez Nicola, while the numerical value is closer to that of Davesne. In the zero-temperature limit we correctly recover the vanishing viscosity associated to a non-relativistic monoatomic gas.Comment: 8 pages, 8 figure

Performance Study of a Torsional Wave Sensor and Cervical Tissue Characterization

A novel torsional wave sensor designed to characterize mechanical properties of soft tissues is presented in this work. Elastography is a widely used technique since the 1990s to map tissue stiffness. Moreover, quantitative elastography uses the velocity of shear waves to achieve the shear stiffness. This technique exhibits significant limitations caused by the difficulty of the separation between longitudinal and shear waves and the pressure applied while measuring. To overcome these drawbacks, the proposed torsional wave sensor can isolate a pure shear wave, avoiding the possibility of multiple wave interference. It comprises a rotational actuator disk and a piezoceramic receiver ring circumferentially aligned. Both allow the transmission of shear waves that interact with the tissue before being received. Experimental tests are performed using tissue mimicking phantoms and cervical tissues. One contribution is a sensor sensitivity study that has been conducted to evaluate the robustness of the new proposed torsional wave elastography (TWE) technique. The variables object of the study are both the applied pressure and the angle of incidence sensor–phantom. The other contribution consists of a cervical tissue characterization. To this end, three rheological models have fit the experimental data and a static independent testing method has been performed. The proposed methodology permits the reconstruction of the mechanical constants from the propagated shear wave, providing a proof of principle and warranting further studies to confirm the validity of the results.This research was supported by the Ministry of Education DPI2014-51870-R, DPI2010-17065 and UNGR15-CE-3664, Ministry of Health DTS15/00093 and PI16/00339, and Junta de Andalucía P11-CTS-8089 projects. Modesto T. López-López acknowledges financial support by the project FIS2013-41821-R (Ministry of Economy and Competitiveness, co-funded by the ERDF, European Union). We acknowledge the collaboration of the members of the Anatomical Pathology Unit of the University Hospital Complex of Granada. Finally, Antonio Callejas is grateful to the University of Granada for the award of an PhD fellowship

Rotavirus infection beyond the gut

The landscape of rotavirus (RV) infection has changed substantially in recent years. Autoimmune triggering has been added to clinical spectrum of this pathology, which is now known to be much broader than diarrhea. The impact of RV vaccines in these other conditions is becoming a growing field of research. The importance of host genetic background in RV susceptibility has been revealed, therefore increasing our understanding of vaccine effectiveness and giving some clues about the limited efficacy of RV vaccines in low-income settings. Also, interaction of RV with intestinal microbiota seems to play a key role in the process of infection vaccine effect. This article reviews current findings on the extraintestinal impact of RV infection and their widening clinical picture, and the recently described mechanisms of host susceptibility to infection and vaccine effectiveness. RV infection is a systemic disease with clinical and pathophysiological implications beyond the gut. We propose an "iceberg" model for this pathology with almost hidden clinical implications away from the gastrointestinal tract and eventually triggering the development of autoimmune diseases. Impact of current vaccines is being influenced by host genetics and gut microbiota interactions and these factors must be taken into account in the development of public health programs

Targeting γ-secretases protect against angiotensin II-induced cardiac hypertrophy

OBJECTIVE: The Notch pathway has been linked to pulmonary hypertension, but its role in systemic hypertension and, in particular in left ventricular hypertrophy (LVH), remains poorly understood. The main objective of this work was to analyse the effect of inhibiting the Notch pathway on the establishment and maintenance of angiotensin II (Ang-II)-induced arterial hypertension and LVH in adult mice with inducible genetic deletion of γ-secretase, and to test preclinically the therapeutic efficacy of γ-secretase inhibitors (GSIs). BASIC METHODS: We analysed Ang-II responses in primary cultures of vascular smooth muscle cells obtained from a novel mouse model with inducible genetic deletion of the γ-secretase complex, and the effects of GSI treatment on a mouse cardiac cell line. We also investigated Ang-II-induced hypertension and LVH in our novel mouse strain lacking the γ-secretase complex and in GSI-treated wild-type mice. Moreover, we analysed vascular tissue from hypertensive patients with and without LVH. MAIN RESULTS: Vascular smooth muscle cells activate the Notch pathway in response to Ang-II both 'in vitro' and 'in vivo'. Genetic deletion of γ-secretase in adult mice prevented Ang-II-induced hypertension and LVH without causing major adverse effects. Treatment with GSI reduced Ang-II-induced hypertrophy of a cardiac cell line 'in vitro' and LVH in wild-type mice challenged with Ang-II. We also report elevated expression of the Notch target HES5 in vascular tissue from hypertensive patients with LVH compared with those without LVH. CONCLUSION: The Notch pathway is activated in the vasculature of mice with hypertension and LVH, and its inhibition via inducible genetic γ-secretase deletion protects against both conditions. Preliminary observations in hypertensive patients with LVH support the translational potential of these findings. Moreover, GSI treatment protects wild-type mice from Ang-II-induced LVH without affecting blood pressure. Our results unveil the potential use of GSIs in the treatment of hypertensive patients with LVH.Juan de la Cierva postdoctoral contract from MINECO [JCI-2011-09663]; MINECO; ProCNIC Foundation; Spanish Ministry of Economy and Competitivity (MINECO) [SAF2013-46663-R]; Instituto de Salud Carlos III [RD12/0042/0028, RD12/0042/0009, MS-00151]; Inserm (jeune chercheur accueilli)S