bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrically Conductive DNA-Inspired Coating for Intracortical Neural Microelectrodes
Authors: Sands Ian , Ersöz Alpaslan , Zhang Wuxia , Zhou Libo , Linthicum Will , Santaniello Sabato , Huey Bryan , Han Martin , Chen Yupeng 
Published: June 2023

AbstractDifferent from conventional electrodes, intracortical neural microelectrodes are the size of one or several neural cells. Due to the limited space for cell-electrode connections, the bio-integration between each neural cell and the electrode surface is critical. To improve bio-integration and electrode functions, various coating materials (such as conductive polymers (CPs), carbon nanotubes (CNTs), and natural hydrogels) have been developed aiming to provide an enhanced interface for neuron recruitment, bio-anchorage, and electrical function. However, synthetic materials usually have limited biocompatibility and/or relatively high cytotoxicity, while biological materials present poor electrical functions. Therefore, current coatings possess biological, functional or electrochemical limitations that are not optimal for intracortical neural microelectrodes. To overcome this obstacle, we developed an electrically conductive coating based on biological molecules, named Janus base nano-coating (JBNc). JBNc is formed by Janus base nanotubes (JBNts) which are a family of nanotubes assembled from engineered DNA base pair units. Based on the long-distance translocation ability of the π electrons of JBNts, we developed them into an electrically conductive coating on the electrode surface. For the first time, we reported the DNA-inspired JBNc had an electrochemical performance that met and exceeded standard metal electrode surface in cyclic voltammetry, impedance spectroscopy, charge injection capacity tests, and neural recording. Moreover, we demonstrated enhanced bio-anchorage and microelectrode interface integration using SEM and AFM. Importantly, we demonstrated enhanced functional response to JBNc microelectrodes with immunohistochemical staining and RNA sequencing (RNAseq) analysis. Using cell viability assays, we also showed the benefits of DNA-mimicking chemistry of Janus base nanomaterials compared to conventional microelectrode coatings. We anticipate that these results will serve as a foundation for the continued development and study of JBNc to enhance interface dynamics and ultimately the performance and reliability of brain microelectrodes.
Visualization of spatial distribution of hemoglobin with various oxygen saturations in small animals using a photoacoustic imaging scanner with a hemispherical detector array
Authors: Asao Yasufumi , Hirano Ryuichiro , Nagae Kenichi , Sekiguchi Hiroyuki , Aiso Sadakazu , Watanabe Shigeaki , Sato Marika , Yagi Takayuki , Kizaka-Kondoh Shinae 
Published: June 2023

AbstractSignificancePhotoacoustic (PA) imaging has garnered considerable attention due to its capability to render vascular images in a label-free manner. Specifically, devices employing a hemispherical detector array (HDA) have been heralded for various clinical applications, owing to their potential to yield high reproducibility three-dimensional images. While high-resolution models utilizing high-frequency sensors have been introduced for animal experimentation, their evaluation has been constrained to a single wavelength. In this study, we demonstrate the applicability of in vivo mouse models for visualizing body oxygen saturation distribution using dual wavelengths.AimWith the aid of our uniquely developed device and analysis software, our primary objective is to map the spatial distribution of the hemoglobin oxygen saturation coefficient (S-factor) through non-invasive in vivo imaging. Subsequently, we aim to observe the temporal alterations within this distribution, specifically assessing changes in hemoglobin oxygen saturation in both normal and tumor vessels over time.ApproachHigh-quality S-factor images were obtained by integrating a newly developed scanning sequence for high contrast with alternate two-wavelength irradiation. Following validation with phantoms, in vivo images were procured in mice. Sequential scanning of the same mouse yielded information about temporal changes. S-factor evaluation was conducted with our photoacoustic image viewer to analyze trends in hemoglobin oxygen saturation.ResultsHigh-contrast images were achieved by increasing the number of integrations during scanning. S-factor images were acquired using both healthy and tumor-bearing mice. Vessels within the liver and kidneys were distinctly reconstructed, and differences in oxygen saturation discriminated between arteries and veins. Repeated measurements on the same mice, both live and post-euthanasia, provided spatiotemporal information, such as a decrease in oxygen saturation after euthanasia or a precipitous drop in oxygen saturation inside the tumor nine days post-cell line transplantation.ConclusionsBy analyzing S-factor images using a photoacoustic imaging system designed for animal experiments, we succeeded in discerning variations in in vivo oxygen saturation. The custom-built system holds promise as a versatile tool for diverse basic research endeavors, as it can seamlessly interface with human clinical applications.
Mesoscale simulations predict the role of synergistic cerebellar plasticity during classical eyeblink conditioning
Authors: Geminiani A , Casellato C , Boele H-J , Pedrocchi A , De Zeeuw C I , D’Angelo E 
Published: June 2023

AbstractAccording to Marr’s motor learning theory, plasticity at the parallel fibre to Purkinje cells synapse (pf-PC) is the main substrate responsible for learning sensorimotor contingencies under climbing fibre control. However, the discovery of multiple forms of plasticity distributed over different cerebellar circuit synapses prompts to remap the cerebellar learning sites. Here, we have simulated classical eyeblink conditioning (CEBC) using an advanced spiking cerebellar model embedding upbound and downbound modules that are subject to multiple plasticity rules. Simulations show that synaptic plasticity regulates the cascade of precise spiking patterns spreading throughout the cerebellar cortex and cerebellar nuclei. CEBC was supported by plasticity in both thepf-PC synapses and in the feedforward inhibitory loop passing through the molecular layer interneurons (MLIs), but only the combined switch-off of both sites of plasticity compromised learning significantly. By differentially engaging climbing fibre information and related forms of synaptic plasticity, both modules contributed to generate a well-timed conditioned response, but it was the downbound module that played the major role in in this process. The outcomes of our simulations closely align with the behavioural and electrophysiological phenotypes of mutant mice suffering from cell-specific mutations that affect processing of their PC or MLI synapses. Our data highlight that a synergy of bidirectional plasticity rules distributed across the cerebellum facilitate finetuning of adaptive associative behaviours at a high spatiotemporal resolution.
Spatial connectivity and marine disease dispersal: missing links in aquaculture carrying capacity debates
Authors: Schmittmann L. , Busch K. , Kluger L. C. 
Published: June 2023

AbstractOne major societal challenge is meeting the constantly increasing demand for (sea)food in a sustainable way. With marine aquaculture on the rise, it is crucial to define limits to aquaculture growth in order to ensure ocean health. Along these lines, the concept of aquaculture carrying capacity (CC) is increasingly intersected with the principles of the ecosystem approach to aquaculture. Its primary aims are to estimate sustainable production potential and limits of locally defined regions. However, the ocean is a fluid environment, subject to large- and small-scale dynamics, including ocean currents, tidal fluctuations, and human action. These dynamics introduce spatial connectivity between aquaculture sites and more distant ecosystems than considered in current CC estimates. We argue that far-reaching effects of aquaculture on the ocean, such as introduction and spread of invasive species and marine diseases, are thus underestimated when providing recommendations. Marine diseases can impact biodiversity, society, and overall ocean health and it is imperative to guide aquaculture development to reduce the risk of marine disease dispersal. We, therefore, suggest to embrace spatial ocean connectivity into the CC concept by using hydrodynamic modelling and dispersal simulations as high-throughput methods to estimate potential impact areas and provide risk assessments. In this work, we focus on the example of dispersing infectious diseases in bivalve farming and discuss ecological as well as social consequences of spatial connectivity. Both are applicable to a wide range of organisms and marine aquaculture systems internationally.SummaryThe concept of aquaculture carrying capacity (CC) aims at defining sustainable limits to aquaculture growth in order to ensure ocean health. Usually, estimations are based on locally defined regions and on the farm-scale. However, interactions of aquaculture with the ocean can have far-reaching effects, such as introduction and spread of invasive species and marine diseases. The ocean is a fluid environment, subject to large- and small-scale dynamics that introduce spatial connectivity between aquaculture sites and more distant ecosystems than considered in current CC estimates. We, therefore, suggest to embrace spatial ocean connectivity into the CC concept by using hydrodynamic modelling and dispersal simulations as high-throughput methods to estimate potential impact areas and provide risk assessments. Here, we focus on the example of dispersing infectious diseases in bivalve farming and discuss ecological as well as social consequences of spatial connectivity. Both are applicable to a wide range of organisms and marine aquaculture systems internationally.
Engineered CD47 protects T cells for enhanced antitumor immunity
Authors: Yamada-Hunter Sean A. , Theruvath Johanna , McIntosh Brianna J. , Freitas Katherine A. , Radosevich Molly T. , Leruste Amaury , Dhingra Shaurya , Martinez-Velez Naiara , Xu Peng , Delaidelli Alberto , Desai Moksha H. , Good Zinaida , Labanieh Louai , Mount Christopher W. , Chen Yiyun , Heitzeneder Sabine , Marjon Kristopher D. , Banuelos Allison , Khan Omair , Huang Jing , Wasserman Savannah L. , Spiegel Jay Y. , Fernandez-Pol Sebastian , Sorensen Poul H. , Monje Michelle , Majzner Robbie G. , Weissman Irving L. , Sahaf Bita , Sotillo Elena , Cochran Jennifer R. , Mackall Crystal L. 
Published: June 2023

AbstractAdoptively transferred T cells and agents designed to block the CD47/SIRPα axis are promising antitumor therapeutics, which activate distinct arms of the immune system. We administered anti-CD47 (αCD47) with adoptively transferred T cells with the goal of enhancing antitumor efficacy but observed rapid macrophage-mediated clearance of T cells expressing chimeric antigen receptors (CARs) or engineered T cell receptors, which blunted therapeutic benefit. αCD47 mediated CAR T clearance was potent and rapid enough to serve as an effective safety switch. To overcome this challenge, we engineered a CD47 variant (47E) that engaged SIRPα and provided a “don’t-eat-me” signal that was not blocked by αCD47 antibodies. TCR or CAR T cells expressing 47Ewere resistant to clearance by macrophages following αCD47, and mediated significant, sustained macrophage recruitment into the TME. Although many of the recruited macrophages manifested an M2-like profile, the combined therapy resulted in synergistic enhancement in antitumor efficacy. This work identifies macrophages as major regulators of T cell persistence and illustrates the fundamental challenge of combining T cell directed therapeutics with those designed to activate macrophages. It further delivers a therapeutic approach capable of simultaneously harnessing the antitumor effects of T cells and macrophages that manifests markedly enhanced potency against solid tumors.
Direct observation of autoubiquitination for an integral membrane ubiquitin ligase in ERAD
Authors: Assainar Basila Moochickal , Ragunathan Kaushik , Baldridge Ryan D. 
Published: June 2023

SummaryThe endoplasmic reticulum associated degradation (ERAD) pathway regulates protein quality control at the endoplasmic reticulum. ERAD of lumenal and membrane proteins requires a conserved E3 ubiquitin ligase, called Hrd1. We do not understand the molecular configurations of Hrd1 that enable autoubiquitination and the subsequent retrotranslocation of misfolded protein substrates from the ER to the cytosol. Here, we have established a generalizable, single-molecule platform that enables high-efficiency labeling, stoichiometry determination, and functional assays for any integral membrane protein. Using this approach, we directly count Hrd1 proteins reconstituted into individual proteoliposomes. We found that Hrd1 assembles in different oligomeric configurations with mostly monomers and dimers detected at limiting dilution. By correlating oligomeric states with ubiquitinationin vitro, we determined that Hrd1 monomers were incapable of autoubiquitination while dimers efficiently assembled polyubiquitin chains. Therefore, our results reveal the minimal composition of a Hrd1 oligomer that is capable of autoubiquitination. Our methods are broadly applicable to studying other complex membrane protein functions using reconstituted bilayer systems.
Enhanced real-time mass spectrometry breath analysis for the diagnosis of COVID-19
Authors: Roquencourt Camille , Salvator Hélène , Bardin Emmanuelle , Lamy Elodie , Farfour Eric , Naline Emmanuel , Devillier Philippe , Grassin-Delyle Stanislas 
Published: June 2023

ABSTRACTBackgroundAlthough rapid screening for and diagnosis of COVID-19 are still urgently needed, most current testing methods are either long, costly, and/or poorly specific. The objective of the present study was to determine whether or not artificial-intelligence-enhanced real-time MS breath analysis is a reliable, safe, rapid means of screening ambulatory patients for COVID-19.MethodsIn two prospective, open, interventional studies in a single university hospital, we used real-time, proton transfer reaction time-of-flight mass spectrometry to perform a metabolomic analysis of exhaled breath from adults requiring screening for COVID-19. Artificial intelligence and machine learning techniques were used to build mathematical models based on breath analysis data either alone or combined with patient metadata.ResultsWe obtained breath samples from 173 participants, of whom 67 had proven COVID-19. After using machine learning algorithms to process breath analysis data and further enhancing the model using patient metadata, our method was able to differentiate between COVID-19-positive and -negative participants with a sensitivity of 98%, a specificity of 74%, a negative predictive value of 98%, a positive predictive value of 72%, and an area under the receiver operating characteristic curve of 0.961. The predictive performance was similar for asymptomatic, weakly symptomatic and symptomatic participants and was not biased by the COVID-19 vaccination status.ConclusionsReal-time, non-invasive, artificial-intelligence-enhanced mass spectrometry breath analysis might be a reliable, safe, rapid, cost-effective, high-throughput method for COVID-19 screening.
Deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial sections
Authors: Schupp Patrick G. , Shelton Samuel J. , Brody Daniel J. , Eliscu Rebecca , Johnson Brett E. , Mazor Tali , Kelley Kevin W. , Potts Matthew B. , McDermott Michael W. , Huang Eric J. , Lim Daniel A. , Pieper Russell O. , Berger Mitchel S. , Costello Joseph F. , Phillips Joanna J. , Oldham Michael C. 
Published: June 2023

AbstractTumors may contain billions of cells including distinct malignant clones and nonmalignant cell types. Clarifying the evolutionary histories, prevalence, and defining molecular features of these cells is essential for improving clinical outcomes, since intratumoral heterogeneity provides fuel for acquired resistance to targeted therapies. Here we present a statistically motivated strategy for deconstructing intratumoral heterogeneity through multiomic and multiscale analysis of serial tumor sections (MOMA). By combining deep sampling of IDH-mutant astrocytomas with integrative analysis of single-nucleotide variants, copy-number variants, and gene expression, we reconstruct and validate the phylogenies, spatial distributions, and transcriptional profiles of distinct malignant clones. By genotyping nuclei analyzed by single-nucleus RNA-seq for truncal mutations, we further show that commonly used algorithms for identifying cancer cells from single-cell transcriptomes may be inaccurate. We also demonstrate that correlating gene expression with tumor purity in bulk samples can reveal optimal markers of malignant cells and use this approach to identify a core set of genes that is consistently expressed by astrocytoma truncal clones, includingAKR1C3, whose expression is associated with poor outcomes in several types of cancer. In summary, MOMA provides a robust and flexible strategy for precisely deconstructing intratumoral heterogeneity and clarifying the core molecular properties of distinct cellular populations in solid tumors.
Probing the neurophysiology of temporal sensitivity in the somatosensory system using the mismatch negativity (MMN) sensory memory paradigm
Authors: Isenstein Emily L. , Freedman Edward G. , Xu Ashley J. , DeAndrea-Lazarus Ian A. , Foxe John J. 
Published: June 2023

ABSTRACTDuration is an amodal feature common to all sensory experiences, but current understanding of sensory-perceptual processing of the temporal qualities of somatosensation remains incomplete. The goal here was to better understand how the brain processes the duration of vibrotactile information, which was assessed by parametrically varying the extent of duration deviance in a somatosensory mismatch negativity (sMMN) paradigm while high-density event-related potential (ERP) recordings were acquired. Healthy young adults (N = 20; aged 18-31 years) received stimulation of the right index fingertip with a 100 ms vibro-tactile input on 80% of trials while the other 20% of trials consisted of deviant stimuli with one of the following durations: 115, 130, 145, or 160 ms. Deviant conditions were presented in separate blocks with deviants pseudo-randomly distributed amongst the 100 ms standards. Participants ignored these inputs while watching a silent movie. Robust sMMN responses, with a dipolar field over the left antero-superior parietal cortex, were detected when deviant stimuli were 130, 145, and 160 ms, but not when they were 115 ms. The amplitudes of the sMMN correlated with individuals’ subsequent abilities to detect duration deviants when actively attempting to discriminate their presence. This simple-to-execute sMMN paradigm holds promise for the assessment of tactile processing differences in clinical populations where tactile sensitivities are a common aspect of the phenotype (e.g., Autism, Fragile-X syndrome).
Synthetic Frizzled agonist and LRP antagonist for high-efficiency Wnt/β-catenin signaling manipulation in organoid cultures andin vivo
Authors: Dai Quanhui , Wang Jiawen , Lin Zihuan , Yu Danni , Yang Hui , Zhang Jiting , Li Xiaoyu , Zeng Junwei , Hu Hao , Ni Chao , Zhao Bing 
Published: June 2023

AbstractWnt/β-catenin signaling and its dysregulation play critical roles in the fate determination of stem cells and the pathology of various diseases. However, the application of translated Wnt ligand in regenerative medicine is hampered by its hydrophobicity and cross-reactivity with Frizzled (FZD) receptors. Here, we generate an engineered water-soluble, FZD subtype-specific agonist, RRP-pbFn, for high-efficiency Wnt/β-catenin signaling activation. In the absence of direct binding to LRP5/6, RRP-pbFn stimulates Wnt/β-catenin signaling more potently than surrogate Wnt. RRP-pbFn supports the growth of a variety of mouse and human organoids, and induces the expansion of liver and intestine progenitorsin vivo. Meanwhile, we develop a synthetic LRP antagonist, RRP-Dkk1c, which exhibits heightened effectiveness in attenuating Wnt/β-catenin signaling activity compared to Dkk1, thereby abolishing the formation of CT26-derived colon cancer xenograftin vivo. Together, these two paired Wnt/β-catenin signaling manipulators hold great promise for biomedical research and potential therapeutics.
Spatial and temporal distribution of ribosomes in single cells reveals aging differences between old and new daughters ofEscherichia coli
Authors: Chao Lin , Chan Chun Kuen , Shi Chao , Rang Camilla U. 
Published: June 2023

ABSTRACTLineages of rod-shaped bacteria such asEscherichia coliexhibit a temporal decline in elongation rate in a manner comparable to cellular or biological aging. The effect results from the production of asymmetrical daughters, one with a lower elongation rate, by the division of a mother cell. The slower daughter compared to the faster daughter, denoted respectively as the old and new daughters, has more aggregates of damaged proteins and fewer expressed gene products. We have examined further the degree of asymmetry by measuring the density of ribosomes between old and new daughters and between their poles. We found that ribosomes were denser in the new daughter and also in the new pole of the daughters. These ribosome patterns match the ones we previously found for expressed gene products. This outcome suggests that the asymmetry is not likely to result from properties unique to the gene expressed in our previous study, but rather from a more fundamental upstream process affecting distribution of ribosomal abundance. Because damage aggregates and ribosomes are both more abundant at the poles ofE. colicells, we suggest that competition for space between the two could explain the reduced ribosomal density in old daughters. Using published values for aggregate sizes and the relationship between ribosomal number and elongation rates, we show that the aggregate volumes could in principle displace quantitatively the amount of ribosomes needed to reduce the elongation rate of the old daughters.IMPORTANCEBacteria exhibit a growth decline in a manner comparable to cellular or biological aging. When a mother bacterium reproduces by binary fission it allocates more damage to one of the two daughters. The extra damage correlates with a slower growth. Thus, a lineage of daughters successively acquiring more damage over generations ages, sometimes even to death under stressful conditions. Aging lineages also have lower levels of expressed gene products. Here we show that the aging process also correlates with lower cellular levels of ribosomes. The identification of a ribosomal effect shows that the aging process is acting at a much more fundamental upstream level. While decreased gene products could have resulted from local regulation of specific genes, a lower ribosomal density affects the entirety of cellular metabolism. Understanding bacterial aging is important because biological aging may have originated in single-celled organisms such asE. coli.