A micropatterned multielectrode shell for 3D spatiotemporal recording from live cells

Microelectrode arrays (MEAs) have proved to be useful tools for characterizing electrically active cells such as cardiomyocytes and neurons. While there exist a number of integrated electronic chips for recording from small populations or even single cells, they rely primarily on the interface between the cells and 2D flat electrodes. Here, an approach that utilizes residual stress‐based self‐folding to create individually addressable multielectrode interfaces that wrap around the cell in 3D and function as an electrical shell‐like recording device is described. These devices are optically transparent, allowing for simultaneous fluorescence imaging. Cell viability is maintained during and after electrode wrapping around the cel and chemicals can diffuse into and out of the self‐folding devices. It is further shown that 3D spatiotemporal recordings are possible and that the action potentials recorded from cultured neonatal rat ventricular cardiomyocytes display significantly higher signal‐to‐noise ratios in comparison with signals recorded with planar extracellular electrodes. It is anticipated that this device can provide the foundation for the development of new‐generation MEAs where dynamic electrode–cell interfacing and recording substitutes the traditional method using static electrodes

Towards comparable assessment of the soil nutrient status across scales-Review and development of nutrient metrics

Unidad de excelencia María de Maeztu CEX2019-000940-MNutrient availability influences virtually every aspect of an ecosystem, and is a critical modifier of ecosystem responses to global change. Although this crucial role of nutrient availability in regulating ecosystem structure and functioning has been widely acknowledged, nutrients are still often neglected in observational and experimental synthesis studies due to difficulties in comparing the nutrient status across sites. In the current study, we explain different nutrient-related concepts and discuss the potential of soil-, plant- and remote sensing-based metrics to compare the nutrient status across space. Based on our review and additional analyses on a dataset of European, managed temperate and boreal forests (ICP [International Co-operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests] Forests dataset), we conclude that the use of plant- and remote sensing-based metrics that rely on tissue stoichiometry is limited due to their strong dependence on species identity. The potential use of other plant-based metrics such as Ellenberg indicator values and plant-functional traits is also discussed. We conclude from our analyses and review that soil-based metrics have the highest potential for successful intersite comparison of the nutrient status. As an example, we used and adjusted a soil-based metric, previously developed for conifer forests across Sweden, against the same ICP Forests data. We suggest that this adjusted and further adaptable metric, which included the organic carbon concentration in the upper 20 cm of the soil (including the organic fermentation-humus [FH] layer), the C:N ratio and of the FH layer, can be used as a complementary tool along with other indicators of nutrient availability, to compare the background nutrient status across temperate and boreal forests dominated by spruce, pine or beech. Future collection and provision of harmonized soil data from observational and experimental sites is crucial for further testing and adjusting the metric

Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia

Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. The extension of chimeric antigen receptor (CAR) T cells (CARTs) to T-ALL remains challenging because the shared expression of target antigens between CARTs and T-ALL blasts leads to CART fratricide. CD1a is exclusively expressed in cortical T-ALL (coT-ALL), a major subset of T-ALL, and retained at relapse. This article reports that the expression of CD1a is mainly restricted to developing cortical thymocytes, and neither CD34+ progenitors nor T cells express CD1a during ontogeny, confining the risk of on-target/off-tumor toxicity. We thus developed and preclinically validated a CD1a-specific CAR with robust and specific cytotoxicity in vitro and antileukemic activity in vivo in xenograft models of coT-ALL, using both cell lines and coT-ALL patient–derived primary blasts. CD1a-CARTs are fratricide resistant, persist long term in vivo (retaining antileukemic activity in re-challenge experiments), and respond to viral antigens. Our data support the therapeutic and safe use of fratricide-resistant CD1a-CARTs for relapsed/refractory coT-ALL.This research was supported by the European Research Council (H2020) (CoG-2014-646903), the Agencia Estatal de Investigacion/European Re- ´ gional Development Fund (SAF2016-80481-R and SAF2016-75442-R), and the Catalunya Government (SGR330 and PERIS 2017) (P.M.), as well as the Asociacion Española Contra el C ´ ancer, Beca FERO, and the ´ ISCIII/FEDER (PI17/01028) (C.B.). P.M. also acknowledges institutional support from the Obra Social La Caixa-Fundacio Josep Carreras. J.G.P. ` holds a Miguel Servet contract (CP15/00014), and O.B.-L. is supported by an AGAUR-FI fellowship from the Catalan Government. P.M. is an investigator of the Spanish Cell Therapy cooperative network (TERCEL).Peer reviewe

3D Microstructured Carbon Nanotube Electrodes for Trapping and Recording Electrogenic Cells

lectrogenic cells such as cardiomyocytes and neurons rely mainly on elec- trical signals for intercellular communication. Microelectrode arrays (MEAs) have been developed for long-term recording of cell signals and stimulation of electrogenic cells under low-cell-stress conditions, providing new insights in the behavior of electrogenic cells and the operation of the brain. To date, MEAs are relying on at or needle-shaped electrode surfaces, mainly due to limitations in the lithographic processes. This paper relies on a previously reported elasto-capillary aggregation process to create 3D carbon nanotube (CNT) MEAs. This study shows that CNTs aggregate in well-shaped struc- tures of similar size as cardiomyocytes are particularly interesting for MEA applications. This is because i) CNT microwells of the right diameter prefer- entially trap individual cardiomyocytes, which facilitates single cell recording without the need for clamping cells or signal deconvolution, and ii) once the cells are trapped inside of the CNT wells, this 3D CNT structure is used as an electrode surrounding the cell, which increases the cell–electrode contact area. As a result, this study nds that the recorded output voltages increase signi cantly (more than 200%). This fabrication process paves the way for future study of complex interactions between electrogenic cells and 3D recording electrodes.status: publishe

Advanced imaging shows extra-articular abscesses in two out of three adult patients with septic arthritis of the native hip joint

<jats:p>Abstract. Background: Septic arthritis (SA) of the native adult hip is a rare orthopaedic emergency requiring prompt diagnosis and treatment. As clinical presentation and laboratory findings are frequently atypical, advanced imaging is often requested. This retrospective study aimed to investigate the prevalence and pattern of extra-articular infectious manifestations and their implications for pre-operative advanced imaging in patients with proven SA of the native hip joint. Methods: Out of 41 patients treated surgically for SA of the native hip during a 16-year period at our tertiary referral hospital, 25 received advanced imaging (computed tomography (CT), magnetic resonance imaging (MRI), or fluorodeoxyglucose positron emission tomography (FDG PET-CT)) prior to initial intervention. For each investigation, a specific set of variables was systematically interpreted, and the most suitable surgical approach was determined. The prognostic value was evaluated by comparing specific outcome measures and the extent of extra-articular involvement. Results: It was found that 32 % of patients had an abscess in one anatomical region, 32 % of patients had abscesses in multiple anatomical regions, and only 36 % of patients had no substantial abscess. Gluteal abscesses were especially common in patients with SA due to contiguous spread. Abscesses in the iliopsoas region were more common in patients with SA due to hematogenous seeding. A combination of several different surgical approaches was deemed necessary to adequately deal with the various presentations. No significant prognostic factors could be identified. Conclusion: We recommend performing advanced imaging in patients with suspected or proven septic arthritis of the native hip joint, as extra-articular abscesses are present in 64 % and might require varying anatomical approaches. </jats:p&gt

A Micropatterned Multielectrode Shell for 3D Spatiotemporal Recording from Live Cells

Microelectrode arrays (MEAs) have proved to be useful tools for characterizing electrically active cells such as cardiomyocytes and neurons. While there exist a number of integrated electronic chips for recording from small populations or even single cells, they rely primarily on the interface between the cells and 2D flat electrodes. Here, an approach that utilizes residual stress‐based self‐folding to create individually addressable multielectrode interfaces that wrap around the cell in 3D and function as an electrical shell‐like recording device is described. These devices are optically transparent, allowing for simultaneous fluorescence imaging. Cell viability is maintained during and after electrode wrapping around the cel and chemicals can diffuse into and out of the self‐folding devices. It is further shown that 3D spatiotemporal recordings are possible and that the action potentials recorded from cultured neonatal rat ventricular cardiomyocytes display significantly higher signal‐to‐noise ratios in comparison with signals recorded with planar extracellular electrodes. It is anticipated that this device can provide the foundation for the development of new‐generation MEAs where dynamic electrode–cell interfacing and recording substitutes the traditional method using static electrodes

Microfluidic interfaces for chronic bidirectional access to the brain

Two-photon polymerization (TPP) is an additive manufacturing technique with micron-scale resolution that is rapidly gaining ground for a range of biomedical applications. TPP is particularly attractive for the creation of microscopic three-dimensional structures in biocompatible and noncytotoxic resins. Here, TPP is used to develop microfluidic interfaces which provide chronic fluidic access to the brain of preclinical research models. These microcatheters can be used for either convection-enhanced delivery (CED) or for the repeated collection of liquid biopsies. In a brain phantom, infusions with the micronozzle result in more localized distribution clouds and lower backflow compared to a control catheter. In mice, the delivery interface enables faster, more precise, and physiologically less disruptive fluid injections. A second microcatheter design enables repeated, longitudinal sampling of cerebrospinal fluid (CSF) over time periods as long as 250 days. Moreover, further in vivo studies demonstrate that the blood-CSF barrier is intact after chronic implantation of the sampling interface and that samples are suitable for downstream molecular analysis for the identification of nucleic acid- or peptide-based biomarkers. Ultimately, the versatility of this fabrication technique implies a great translational potential for simultaneous drug delivery and biomarker tracking in a range of human neurological diseases. The limited passage of molecules between the blood and the brain poses a major challenge for drug research and therapy. To address this, the authors use ultrahigh resolution additive manufacturing to develop a miniaturized microcatheter platform for faster, more predictable, and physiologically nondisruptive fluid delivery as well as reliable fluid collection, at rates and with long-term stability not reported before

Multiplexed Surface Electrode Arrays Based on Metal Oxide Thin‐Film Electronics for High‐Resolution Cortical Mapping

Abstract Electrode grids are used in neuroscience research and clinical practice to record electrical activity from the surface of the brain. However, existing passive electrocorticography (ECoG) technologies are unable to offer both high spatial resolution and wide cortical coverage, while ensuring a compact acquisition system. The electrode count and density are restricted by the fact that each electrode must be individually wired. This work presents an active micro‐electrocorticography (µECoG) implant that tackles this limitation by incorporating metal oxide thin‐film transistors (TFTs) into a flexible electrode array, allowing to address multiple electrodes through a single shared readout line. By combining the array with an incremental‐ΔΣ readout integrated circuit (ROIC), the system is capable of recording from up to 256 electrodes virtually simultaneously, thanks to the implemented 16:1 time‐division multiplexing scheme, offering lower noise levels than existing active µECoG arrays. In vivo validation is demonstrated acutely in mice by recording spontaneous activity and somatosensory evoked potentials over a cortical surface of ≈8×8 mm2. The proposed neural interface overcomes the wiring bottleneck limiting ECoG arrays, holding promise as a powerful tool for improved mapping of the cerebral cortex and as an enabling technology for future brain‐machine interfaces

Towards comparable assessment of the soil nutrient status across scales—Review and development of nutrient metrics

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Towards comparable assessment of the soil nutrient status across scales : review and development of nutrient metrics

Unidad de excelencia María de Maeztu CEX2019-000940-MNutrient availability influences virtually every aspect of an ecosystem, and is a critical modifier of ecosystem responses to global change. Although this crucial role of nutrient availability in regulating ecosystem structure and functioning has been widely acknowledged, nutrients are still often neglected in observational and experimental synthesis studies due to difficulties in comparing the nutrient status across sites. In the current study, we explain different nutrient-related concepts and discuss the potential of soil-, plant- and remote sensing-based metrics to compare the nutrient status across space. Based on our review and additional analyses on a dataset of European, managed temperate and boreal forests (ICP [International Co-operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests] Forests dataset), we conclude that the use of plant- and remote sensing-based metrics that rely on tissue stoichiometry is limited due to their strong dependence on species identity. The potential use of other plant-based metrics such as Ellenberg indicator values and plant-functional traits is also discussed. We conclude from our analyses and review that soil-based metrics have the highest potential for successful intersite comparison of the nutrient status. As an example, we used and adjusted a soil-based metric, previously developed for conifer forests across Sweden, against the same ICP Forests data. We suggest that this adjusted and further adaptable metric, which included the organic carbon concentration in the upper 20 cm of the soil (including the organic fermentation-humus [FH] layer), the C:N ratio and of the FH layer, can be used as a complementary tool along with other indicators of nutrient availability, to compare the background nutrient status across temperate and boreal forests dominated by spruce, pine or beech. Future collection and provision of harmonized soil data from observational and experimental sites is crucial for further testing and adjusting the metric