Variation and plasticity in life-history traits and fitness of wild Arabidopsis thaliana populations are not related to their genotypic and ecological diversity

[Background]: Despite its implications for population dynamics and evolution, the relationship between genetic and phenotypic variation in wild populations remains unclear. Here, we estimated variation and plasticity in lifehistory traits and ftness of the annual plant Arabidopsis thaliana in two common garden experiments that difered in environmental conditions. We used up to 306 maternal inbred lines from six Iberian populations characterized by low and high genotypic (based on whole-genome sequences) and ecological (vegetation type) diversity.[Results]: Low and high genotypic and ecological diversity was found in edge and core Iberian environments, respectively. Given that selection is expected to be stronger in edge environments and that ecological diversity may enhance both phenotypic variation and plasticity, we expected genotypic diversity to be positively associated with phenotypic variation and plasticity. However, maternal lines, irrespective of the genotypic and ecological diver‑ sity of their population of origin, exhibited a substantial amount of phenotypic variation and plasticity for all traits. Furthermore, all populations harbored maternal lines with canalization (robustness) or sensitivity in response to harsher environmental conditions in one of the two experiments.[Conclusions]: Overall, we conclude that the environmental attributes of each population probably determine their genotypic diversity, but all populations maintain substantial phenotypic variation and plasticity for all traits, which represents an asset to endure in changing environments.This research was funded by grants CGL2016-77720-P and PID2019-104135GB-I00 to FXP, and grant PID2022-136893NB-I00 to CA-B, from the Agencia Estatal de Investigación of Spain (AEI/10.13039/501100011033) and the Fondo Europeo de Desarrollo Regional (FEDER, UE).Peer reviewe

Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation

Human metastatic cholangiocarcinoma; Xenografts; TumoroidsColangiocarcinoma metastàtic humà; Xenoempelts; TumoroidesColangiocarcinoma metastásico humano; Xenoinjertos; TumoroidesPurpose: Cholangiocarcinoma (CCA) is usually diagnosed at advanced stages, with limited therapeutic options. Preclinical models focused on unresectable metastatic CCA are necessary to develop rational treatments. Pathogenic mutations in IDH1/2, ARID1A/B, BAP1, and BRCA1/2 have been identified in 30%–50% of patients with CCA. Several types of tumor cells harboring these mutations exhibit homologous recombination deficiency (HRD) phenotype with enhanced sensitivity to PARP inhibitors (PARPi). However, PARPi treatment has not yet been tested for effectiveness in patient-derived models of advanced CCA. Experimental Design: We have established a collection of patient-derived xenografts from patients with unresectable metastatic CCA (CCA_PDX). The CCA_PDXs were characterized at both histopathologic and genomic levels. We optimized a protocol to generate CCA tumoroids from CCA_PDXs. We tested the effects of PARPis in both CCA tumoroids and CCA_PDXs. Finally, we used the RAD51 assay to evaluate the HRD status of CCA tissues. Results: This collection of CCA_PDXs recapitulates the histopathologic and molecular features of their original tumors. PARPi treatments inhibited the growth of CCA tumoroids and CCA_PDXs with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1. In line with these findings, only CCA_PDX and CCA patient biopsy samples with mutations of BRCA2 showed RAD51 scores compatible with HRD. Conclusions: Our results suggest that patients with advanced CCA with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1, are likely to benefit from PARPi therapy. This collection of CCA_PDXs provides new opportunities for evaluating drug response and prioritizing clinical trials.This work was supported by grants from the Fundació Marató TV3 awarded to T. Macarulla, M. Melé, and S. Peiró; BeiGene research grant awarded to T. Macarulla and S. Peiró; AECC (INVES20036TIAN), Ramón y Cajal investigator program (RYC2020-029098-I), Proyecto de I+D+i (PID2019-108008RJ-I00), and FERO Foundation grant awarded to T.V. Tian; Proyecto de Investigación en Salud from the Instituto de Salud Carlos III (ISCIII) (PI20/00898) awarded to T. Macarulla; FIS/FEDER from the Instituto de Salud Carlos III (ISCIII) (PI12/01250; CP08/00223; PI16/00253 and CB16/12/00449) awarded to S. Peiró; and Ramón y Cajal investigator program (RYC-2017-22249) awarded to M. Melé. Q. Serra-Camprubí is a recipient of the Ph.D. fellowship from La Caixa Foundation (LCF/PR/PR12/51070001). A. Llop-Guevara was supported by the AECC (INVES20095LLOP) and V. Serra by the ISCIII (CPII19/00033). E.J. Arenas was funded by the AECC (POSTD211413AREN). J. Arribas is funded by the Instituto de Salud Carlos III (AC15/00062, CB16/12/00449, and PI22/00001). This publication is based upon the work of COST Action CA18122, European Cholangiocarcinoma Network, supported by the COST (European Cooperation in Science and Technology, www.cost.eu), a funding agency for research and innovation networks. The authors would like to thank Dr. V.A. Raker for manuscript editing and Drs. N. Herranz and J. Mateo for scientific discussions. The authors acknowledge the infrastructure and support of the FERO Foundation, La Caixa Foundation, and the Cellex Foundation

Histology of gill, liver and kidney in juvenile fish Colossoma macropomum exposed to three temperatures

Colossoma macropomum es uno de los peces tropicales de agua dulce con mayor éxito en el cultivo en aguas continentales tropicales. Se realizó una evaluación histológica de branquias, hígado y riñón de este pez expuesto a tres temperaturas (T18, T29 y T35ºC). Se utilizaron 18 ejemplares juveniles con índices biométricos de 17.87±7.88cm y 87.69±34.23g. Los análisis histológicos fueron hechos de acuerdo a técnicas previamente descritas. Se encontró que las branquias, el hígado y el riñón de los peces T29 presentaron citoarquitectura normal. Por el contrario, en las branquias de los peces T18, se observaron gotas lipídicas inmersas en el tejido branquial; los peces T35 presentaron desorganización en la estructura del tejido branquial y necrosis celular. El hígado de los peces T18, mostró hepatocitos claros y oscuros y el de T35, presentó células con granulaciones citoplasmáticas y daño en la membrana plasmática. En el riñón de los T18, se observaron alteraciones en la distribución del tejido hematopoyético. La característica más resaltante en el riñón de los peces T35, fue la desorganización del tejido glomerular. En conclusión, la temperatura de 18°C se puede considerar crítica para la cachama y la de 35ºC severa. De los tres órganos evaluados, el hígado y las branquias resultaron ser los más sensibles a los daños inducidos por las temperaturas en esta especie.Water temperature is an important factor that affects growth and antioxidant enzyme activities in fish, and when adverse, it may trigger diseases in fish populations. C. macropomum is a freshwater neotropical fish widely distributed in South America and abundant in river basins as the Amazon and Orinoco. It is highly used for intensive aquaculture development and is a very important product for the local riverside economy in Venezuela. The purpose of our study was to examine the water temperature effect on gills, liver and kidneys of juvenile fishes of C. macropomum. Eighteen juveniles with biometrical index of 17.87±7.88cm and 87.69±34.23g were respectively exposed to three culture temperatures (T18, T29 and T35ºC) during a period of 21 days. Histological analyses on gills, liver and kidney were made according to standard methodologies. Our results showed that these tissues exhibited normal citoarchitecture at T29. On the contrary, T18-gills displayed brachiallipid droplets inside brachial epithelium; and disorganization in the brachial tissue was observed at T35. Furthermore, we observed two kinds of hepatocytes (dark and light) on T18°C-liver. The T35-liver samples showed cytoplasmatic granulation and damages in cytoplasmatic membrane. Kidney samples from T18 observed alterations in the cellular distribution of the hematopoietic tissue; while, at T35, the most important feature observed was the disorganization of the glomerular structure. We concluded that T18 and T35 are respectively critical and severe temperatures to C. macropomum; besides, the most sensible tissues to changes induced by temperature in this species were the liver and gills

Histología de branquias, hígado y riñón de juveniles del pez neotropical Colossoma macropomum (Characiformes, Characidae) expuesto a tres temperaturas Histology of gill, liver and kidney in juvenile fish Colossoma macropomum exposed to three temperatures

Colossoma macropomum es uno de los peces tropicales de agua dulce con mayor éxito en el cultivo en aguas continentales tropicales. Se realizó una evaluación histológica de branquias, hígado y riñón de este pez expuesto a tres temperaturas (T18, T29 y T35ºC). Se utilizaron 18 ejemplares juveniles con índices biométricos de 17.87±7.88cm y 87.69±34.23g. Los análisis histológicos fueron hechos de acuerdo a técnicas previamente descritas. Se encontró que las branquias, el hígado y el riñón de los peces T29 presentaron citoarquitectura normal. Por el contrario, en las branquias de los peces T18, se observaron gotas lipídicas inmersas en el tejido branquial; los peces T35 presentaron desorganización en la estructura del tejido branquial y necrosis celular. El hígado de los peces T18, mostró hepatocitos claros y oscuros y el de T35, presentó células con granulaciones citoplasmáticas y daño en la membrana plasmática. En el riñón de los T18, se observaron alteraciones en la distribución del tejido hematopoyético. La característica más resaltante en el riñón de los peces T35, fue la desorganización del tejido glomerular. En conclusión, la temperatura de 18°C se puede considerar crítica para la cachama y la de 35ºC severa. De los tres órganos evaluados, el hígado y las branquias resultaron ser los más sensibles a los daños inducidos por las temperaturas en esta especie.<br>Water temperature is an important factor that affects growth and antioxidant enzyme activities in fish, and when adverse, it may trigger diseases in fish populations. C. macropomum is a freshwater neotropical fish widely distributed in South America and abundant in river basins as the Amazon and Orinoco. It is highly used for intensive aquaculture development and is a very important product for the local riverside economy in Venezuela. The purpose of our study was to examine the water temperature effect on gills, liver and kidneys of juvenile fishes of C. macropomum. Eighteen juveniles with biometrical index of 17.87±7.88cm and 87.69±34.23g were respectively exposed to three culture temperatures (T18, T29 and T35ºC) during a period of 21 days. Histological analyses on gills, liver and kidney were made according to standard methodologies. Our results showed that these tissues exhibited normal citoarchitecture at T29. On the contrary, T18-gills displayed brachiallipid droplets inside brachial epithelium; and disorganization in the brachial tissue was observed at T35. Furthermore, we observed two kinds of hepatocytes (dark and light) on T18°C-liver. The T35-liver samples showed cytoplasmatic granulation and damages in cytoplasmatic membrane. Kidney samples from T18 observed alterations in the cellular distribution of the hematopoietic tissue; while, at T35, the most important feature observed was the disorganization of the glomerular structure. We concluded that T18 and T35 are respectively critical and severe temperatures to C. macropomum; besides, the most sensible tissues to changes induced by temperature in this species were the liver and gills

Flexible Magnetoreceptor with Tunable Intrinsic Logic for On-Skin Touchless Human-Machine Interfaces

Artificial magnetoception is a new and yet to be explored path for humans to interact with the surroundings. This technology is enabled by thin film magnetic field sensors embedded in a soft and flexible format to constitute magnetosensitive electronic skins (e-skins). Being limited by the sensitivity to in-plane magnetic fields, magnetosensitive e-skins are restricted to basic proximity and angle sensing and are not used as switches or logic elements of interactive wearable electronics. Here, a novel magnetoreceptive platform for on-skin touchless interactive electronics based on flexible spin valve switches with sensitivity to out-of-plane magnetic fields is demonstrated. The technology relies on all-metal Co/Pd-based spin valves with a synthetic antiferromagnet possessing perpendicular magnetic anisotropy. The flexible magnetoreceptors act as logic elements, namely momentary and permanent (latching) switches. The switches maintain their performance even upon bending to a radius of less than 3.5&nbsp;mm and withstand repetitive bending for hundreds of cycles. Here, flexible switches are integrated in on-skin interactive electronics and their performance as touchless human-machine interfaces is demonstrated, which are intuitive to use, energy efficient, and insensitive to external magnetic disturbances. This technology offers qualitatively new functionalities for electronic skins and paves the way towards full-fledged on-skin touchless interactive electronics

Data publication: Impedimetric Nanobiosensor for the Detection of SARS-CoV-2 Antigens and Antibodies

This publication includes datasets of electrical impedance spectroscopy measurements of the response of functionalized gold nanowires when interacting with antigens and antibodies related to SARS-CoV-2 in physiological conditions and in human plasma samples

Chemical Vapor Deposition and High-Resolution Patterning of a Highly Conductive Two-Dimensional Coordination Polymer Film

Crystalline coordination polymers with high electrical conductivities and charge carrier mobilities might open new opportunities for electronic devices. However, current solvent-based synthesis methods hinder compatibility with microfabrication standards. Here, we describe a solvent-free chemical vapor deposition method to prepare high-quality films of the two-dimensional conjugated coordination polymer Cu-BHT (BHT = benzenehexanothiolate). This approach involves the conversion of a metal oxide precursor into Cu-BHT nanofilms with a controllable thickness (20–85 nm) and low roughness (<10 nm) through exposure to the vaporized organic linker. Moreover, the restricted metal ion mobility during the vapor–solid reaction enables high-resolution patterning via both bottom-up lithography, including the fabrication of micron-sized Hall bar and electrode patterns to accurately evaluate the conductivity and mobility values of the Cu-BHT films

A practical approach for the compassionate use of convalescent plasma in patients with severe COVID-19 in developing countries

The COVID-19 pandemic has affected 187 countries, representing a global public health problem. The increasing number of critically ill patients and deaths have fueled a desperate search for treatments that can halt the course of the disease. Currently, there are several experimental therapies with demonstrated in vitro activity against COVID-19 used in clinical practice, including hydroxychloroquine, remdesivir, interleukin-6 pathway inhibitors, and convalescent plasma; however, to date no agent has proven efficacy against COVID-19. In the case of convalescent plasma, this therapy consists in obtaining neutralizing antibodies from previously infected individuals by plasmapheresis and administering them to patients with severe disease. Recently, the use of convalescent plasma has shown promising results in preliminary studies, with case series reporting a decrease in temperature, and viral load, as well as improvement in clinical parameters among patients receiving this treatment. However, there are still unmet needs regarding the safety profile, tolerability, dosage, and timing this therapy should be given. Based on this, the objective of our study was to develop and propose a practical approach for the compassionate use of convalescent plasma for the treatment of patients with severe COVID-19, given the constrains and limitations of developing countries. We encourage health professionals in developing countries to use the current evidence and approaches to experimental treatments for patients with COVID-19, adapting them to their conditions, and always based on a thorough risk-benefit evaluation for each patient, and whenever possible to design and promote the much needed research in this field