A hybrid physics-based and data-driven framework for cellular biological systems: Application to the morphogenesis of organoids

How cells orchestrate their cellular functions remains a crucial question to unravel how they organize in different patterns. We present a framework based on artificial intelligence to advance the understanding of how cell functions are coordinated spatially and temporally in biological systems. It consists of a hybrid physics-based model that integrates both mechanical interactions and cell functions with a data-driven model that regulates the cellular decision-making process through a deep learning algorithm trained on image data metrics. To illustrate our approach, we used data from 3D cultures of murine pancreatic ductal adenocarcinoma cells (PDAC) grown in Matrigel as tumor organoids. Our approach allowed us to find the underlying principles through which cells activate different cell processes to self-organize in different patterns according to the specific microenvironmental conditions. The framework proposed here expands the tools for simulating biological systems at the cellular level, providing a novel perspective to unravel morphogenetic patterns

Brucella spp. Lumazine synthase as a novel immunomodulator to produce egg yolk antibodies

Lumazine synthase from Brucella spp. (BLS) is a highly immunogenic decameric protein. It has been previously described as a carrier of peptides or proteins to increase their immunogenicity in different animal species, but its activity has never been evaluated in chickens. In this work, the use of BLS to improve the antibody response against bovine rotavirus (BRV) VP8d protein in laying hens was assessed. VP8d is the inner domain of the VP8 spike protein which preserves the sialic acid binding activity and the neutralizing epitopes present in the viral protein. Hens were immunized three times with 2 μg of VP8d alone or fused to BLS. Hens inoculated with BLSVP8d developed higher antibody titers (evaluated by ELISA and viral neutralization test) than hens immunized either with VP8d alone or the mixture of VP8d and BLS. Furthermore, IgY antibodies against BLSVP8d were able to fully protect mice against challenge with virulent BRV in a dose-depent-manner. Overall, these results demonstrate that BLS is a potent immonumodulator that enhances the antibody response in hens, thus increasing the concentration of specific IgY in the egg yolk, one of the main issues to be adressed in order to improve the use of the IgY technology.Instituto de VirologíaFil: Bellido, Demian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Chacana, Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Mozgovoj, Marina Valeria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Gonzalez, Diego. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Goldbaum, Fernando Alberto. Fundación Instituto Leloir; ArgentinaFil: Wigdorovitz, Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Dus Santos, Maria Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentin

Sardines at a junction: seascape genomics reveals ecological and oceanographic drivers of variation in the {NW} Mediterranean Sea

By evaluating genetic variation across the entire genome, one can address existing questions in a novel way while raising new ones. The latter includes how different local environments influence adaptive and neutral genomic variation within and among populations, providing insights into local adaptation of natural populations and their responses to global change. Here, under a seascape genomic approach, ddRAD data of 4609 single nucleotide polymorphisms (SNPs) from 398 sardines (Sardina pilchardus) collected in 11 Mediterranean and one Atlantic site were generated. These were used along with oceanographic and ecological information to detect signals of adaptive divergence with gene flow across environmental gradients. The studied sardines constitute two clusters (FST = 0.07), a pattern attributed to outlier loci, highlighting putative local adaptation. The trend in the number of days with sea surface temperature above 19°C, a critical threshold for successful sardine spawning, was crucial at all levels of population structuring with implications on the species' key biological processes. Outliers link candidate SNPs to the region's environmental heterogeneity. Our findings provide evidence for a dynamic equilibrium in which population structure is maintained by physical and ecological factors under the opposing influences of migration and selection. This dynamic in a natural system warrants continuous monitoring under a seascape genomic approach that might benefit from a temporal and more detailed spatial dimension. Our results may contribute to complementary studies aimed at providing deeper insights into the mechanistic processes underlying population structuring. Those are key to understanding and predicting future changes and responses of this highly exploited species in the face of climate change

Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B

The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control. Clinical parameters, proviral DNA, host HLA genetics and measures of humoral and cellular immunity were evaluated. A sieve effect analysis was conducted comparing pre-treatment viral sequences to breakthrough viruses after STI. Our results show that a reduced proviral HIV-1 DNA at study entry was independently associated with two virological parameters, delayed HIV-1 RNA rebound (p = 0.029) and lower peak viremia after treatment cessation (p = 0.019). Reduced peak viremia was also positively correlated with a decreased number of HLA class I allele associated polymorphisms in Gag sequences in the rebounding virus population (p = 0.012). Our findings suggest that proviral DNA levels and the number of HLA-associated Gag polymorphisms may have an impact on the clinical outcome of STI. Incorporation of these parameters in future therapeutic vaccine trials may guide refined immunogen design and help conduct safer STI approaches

Development of a few TW Ti:Sa laser system at 100 Hz for proton acceleration

[EN] We report the development of a table-top high peak power Titanium:Sapphire (Ti:Sa) CPA laser working at 100 Hz capable of delivering 205 mJ, 55 fs pulses. Every amplification stage is pumped by Nd-doped solid-state lasers and fully powered by diodes. Thermal effects in the Ti:Sa amplifiers are compensated passively with optics. This system is intended to be used for proton acceleration experiments at high repetition rates.Centro para el Desarrollo Tecnológico Industrial (CDTI, Spain) within the INNPRONTA program, Grant no. IPT-20111027.Lera, R.; Bellido-Millán, PJ.; Sánchez, I.; Mur, P.; Seimetz, M.; Benlloch Baviera, JM.; Roso, L.... (2019). Development of a few TW Ti:Sa laser system at 100 Hz for proton acceleration. Applied Physics B. 125(1):1-8. https://doi.org/10.1007/s00340-018-7113-8S181251P. Zeitoun, G. Faivre, S. Sebban, T. Mocek, A. Hallou, M. Fajardo, D. Aubert, P. Balcou, F. Burgy, D. Douillet, S. Kazamias, G. de Lachèze-Murel, T. Lefrou, S. le Pape, P. Mercère, H. Merdji, A.S. Morlens, J.P. Rousseau, C. Valentin, Nature 431(7007), 426–429 (2004)V. Malka, S. Fritzler, E. Lefebvre, M.-M. Aleonard, F. Burgy, J.-P. Chambaret, J.-F. Chemin, K. Krushelnick, G. Malka, S.P.D. Mangles, Z. Najmudin, M. Pittman, J.-P. Rousseau, J.-N. Scheurer, B. Walton, A.E. Dangor, Science 298(5598), 1596–1600 (2002)H. Daido, M. Nishiuchi, A.S. Pirozhkov, Rep. Progress Phys. 75(5), 056401 (2012)A. Macchi, M. Borghesi, M. Passoni, Rev. Mod. Phys. 85, 751–793 (2013)T. Tajima, J.M. Dawson, Phys. Rev. Lett. 43, 267–270 (1979)M. Noaman-ul Haq, H. Ahmed, T. Sokollik, L. Yu, Z. Liu, X. Yuan, F. Yuan, M. Mirzaie, X. Ge, L. Chen, J. Zhang, Phys. Rev. Accel. Beams 20, 041301 (2017)D. Strickland, G. Mourou, Opt. Commun. 53(3), 219–221 (1985)G. Cheriaux, B. Walker, L.F. Dimauro, P. Rousseau, F. Salin, J.P. Chambaret, Opt. Lett. 21(6), 414–416 (1996)P. Tournois, Opt. Commun. 140(4), 245–249 (1997)R. Soulard, A. Brignon, S. Raby, E. Durand, R. Moncorgé, Appl. Phys. B 106(2), 295–300 (2012)J. Liu, L. Ge, L. Feng, H. Jiang, H. Su, T. Zhou, J. Wang, Q. Gao, J. Li, Chin. Opt. Lett. 14(5), 051404 (2016)A. Maleki, M.K. Tehrani, H. Saghafifar, M.H.M. Dindarlu, H. Ebadian, Laser Phys. 26(2), 025003 (2016)R. Lera, F. Valle-Brozas, S. Torres-Peiró, A.R. de-la Cruz, M. Galán, P. Bellido, M. Seimetz, J.M. Benlloch, L. Roso, Appl. Opt. 55(33), 9573–9576 (2016)R. Lausten, P. Balling, J. Opt. Soc. Am. B 20(7), 1479–1485 (2003)I. Nam, M. Kim, T.H. Lee, S.W. Lee, H. Suk, Curr. Appl. Phys. 15(4), 468–472 (2015)E. Treacy, IEEE J. Quantum Electron. 5(9), 454–458 (1969)A. Trisorio, S. Grabielle, M. Divall, N. Forget, C.P. Hauri, Opt. Lett. 37(14), 2892–2894 (2012)Y.-H. Cha, Y.-W. Lee, S.M. Nam, J.M. Han, Y.J. Rhee, B.D. Yoo, B.C. Lee, Y.U. Jeong, Appl. Opt. 46(28), 6854–6858 (2007)P. Bellido, R. Lera, M. Seimetz, A.R. de la Cruz, S. Torres-Peiró, M. Galán, P. Mur, I. Sánchez, R. Zaffino, L. Vidal, A. Soriano, S. Sánchez, F. Sánchez, M. Rodríguez-Álvarez, J. Rigla, L. Moliner, A. Iborra, L. Hernández, D. Grau-Ruiz, A. González, J. García-Garrigos, E. Díaz-Caballero, P. Conde, A. Aguilar, L. Roso, J. Benlloch, J. Instrum. 12(05), T05001 (2017

Conduction system pacing vs. biventricular pacing in patients with ventricular dysfunction and AV block

Background: It is unknown whether His-Purkinje conduction system pacing (HPCSP), as either His bundle or left bundle branch pacing, could be an alternative to cardiac resynchronization therapy (BiVCRT) for patients with left ventricular dysfunction needing ventricular pacing due to atrioventricular block. The aim of the study is to compare the echocardiographic response and clinical improvement between HPCSP and BiVCRT. Methods: Consecutive patients who successfully received HPCSP were compared with a historical cohort of BiVCRT patients. Patients were 1:1 matched by age, LVEF, atrial fibrillation, renal function and cardiomyopathy type. Responders were defined as patients who survived, did not require heart transplantation and increased LVEF ≥5 points at 6-month follow-up. Results: HPCSP was successfully achieved in 92.5% (25/27) of patients. During follow-up, 8% (2/25) of HPCSP patients died and 4% (1/25) received a heart transplant, whereas 4% (1/25) of those in the BiVCRT cohort died. LVEF improvement was 10% ± 8% HPCSP versus 7% ± 5% BiVCRT (p = .24), and the percentage of responders was 76% (19/25) HPCSP versus 64% (16/25) BiVCRT (p = .33). Among survivors, the percentage of patients who improved from baseline II-IV mitral regurgitation (MR) to 0-I MR was 9/11 (82%) versus 2/8 (25%) (p = .02). Compared to those with BiVCRT, patients with HPCSP achieved better NYHA improvement: 1 point versus 0.5 (OR 0.34; p = .02). Conclusion: HPCSP in patients with LVEF ≤45% and atrioventricular block improved the LVEF and induced a response similar to that of BiVCRT. HPCSP significantly improved MR and NYHA functional class. HPCSP may be an alternative to BiVCRT in these patients. (Figure 1. Central Illustration). [Figure: see text]

Changes in Life History Traits of Small Pelagic Fish in the Western Mediterranean Sea

21 pages, 8 figures, 3 tables, supplementary material https://www.frontiersin.org/articles/10.3389/fmars.2021.570354/full#supplementary-material.-- Data Availability Statement: The datasets presented in this article are not readily available because the dataset is available by request to the Spanish Institute of Oceanography. Requests to access the datasets should be directed to [email protected] pelagic fish (SPF) in the western Mediterranean Sea are key elements of the marine food web and are important in terms of biomass and fisheries catches. Significant declines in biomass, landings, and changes in the age/size structure of sardine Sardina pilchardus and anchovy Engraulis encrasicolus have been observed in recent decades, particularly in the northern area of the western Mediterranean Sea. To understand the different patterns observed in SPF populations, we analyzed key life history traits [total length at age, length at maturity, gonadosomatic index (GSI), and body condition (Kn)] of sardine and anchovy collected between 2003 and 2017, from different fishing harbors distributed along a latitudinal gradient from northern to southern Spain. We used Generalized Linear Models (GLM) to estimate the length at maturity and Generalized Additive Models (GAMs) to test the relationship with environmental variables (seawater temperature, water currents, and net primary productivity). The life history traits of both species presented seasonal, interannual and latitudinal differences with a clear decline in length at age, length at first maturity, and body condition, for both species in the northern part of the study area. In the southern part, on the contrary, life history traits did not present a clear temporal trend. The environmental conditions partially explained the long-term changes in life history traits, but the selected variables differed between areas, highlighting the importance of regional oceanographic conditions to understand the dynamics of small pelagic fish. The truncated length-at-age pattern for both species with the disappearance of the larger individuals of the population could have contributed to the poor condition of small pelagic fish populations in the northern part of the western Mediterranean Sea in recent years. In the south area, recent declines in body condition for sardine and anchovy were observed and could be a possible first sign for future population declines. This study highlights the importance of understanding the trade-off between the energy invested in reproduction, maintenance and growth at seasonal and interannual level to advance our knowledge on how environmental and human pressures influence population dynamics of small pelagic fish at local and regional scalesThis study was carried out within the Spanish Research project PELWEB (CTM2017-88939-R) funded by Spanish Ministry of Science, Innovation and Universities and the European Research Contract SPELMED (SC NR 02-TENDER EASME/EMFF/2016/032XXX) funded by EC EASME. Fisheries data collection has been co-funded by the EU through the European Maritime and Fisheries Fund (EMFF) within the National Program of collection, management and use of data in the fisheries sector and support for scientific advice regarding the Common Fisheries Policy (Regulation, EU 2017/1004)With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S)Peer reviewe

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO