Genetically targeted chemical assembly of functional materials in living cells, tissues, and animals

The structural and functional complexity of multicellular biological systems, such as the brain, are beyond the reach of human design or assembly capabilities. Cells in living organisms may be recruited to construct synthetic materials or structures if treated as anatomically defined compartments for specific chemistry, harnessing biology for the assembly of complex functional structures. By integrating engineered-enzyme targeting and polymer chemistry, we genetically instructed specific living neurons to guide chemical synthesis of electrically functional (conductive or insulating) polymers at the plasma membrane. Electrophysiological and behavioral analyses confirmed that rationally designed, genetically targeted assembly of functional polymers not only preserved neuronal viability but also achieved remodeling of membrane properties and modulated cell type–specific behaviors in freely moving animals. This approach may enable the creation of diverse, complex, and functional structures and materials within living systems.

Download Full-text

From many to one: Meditation and the plasticity of the predictive mind

10.31234/osf.io/5sw6m ◽

2020 ◽

Author(s):

Ruben Laukkonen ◽

Heleen A Slagter

Keyword(s):

Cognitive Enhancement ◽

The Self ◽

Predictive Processing ◽

Focused Attention ◽

Conceptual Processing ◽

Current State ◽

Contemplative Science ◽

Open Monitoring ◽

Living Organisms ◽

The Brain

How profoundly can humans change their own minds? In this paper we offer a unifying account of meditation under the predictive processing view of living organisms. We start from relatively simple axioms. First, the brain is an organ that serves to predict based on past experience, both phylogenetic and ontogenetic. Second, meditation serves to bring one closer to the here and now by disengaging from anticipatory processes. We propose that practicing meditation therefore gradually reduces predictive processing, in particular counterfactual cognition—the tendency to construct abstract and temporally deep representations—until all conceptual processing falls away. Our Many- to-One account also places three main styles of meditation (focused attention, open monitoring, and non-dual meditation) on a single continuum, where each technique progressively relinquishes increasingly engrained habits of prediction, including the self. This deconstruction can also make the above processes available to introspection, permitting certain insights into one’s mind. Our review suggests that our framework is consistent with the current state of empirical and (neuro)phenomenological evidence in contemplative science, and is ultimately illuminating about the plasticity of the predictive mind. It also serves to highlight that contemplative science can fruitfully go beyond cognitive enhancement, attention, and emotion regulation, to its more traditional goal of removing past conditioning and creating conditions for potentially profound insights. Experimental rigor, neurophenomenology, and no-report paradigms combined with neuroimaging are needed to further our understanding of how different styles of meditation affect predictive processing and the self, and the plasticity of the predictive mind more generally.

Download Full-text

Recent advances in skin collagen: functionality and non-medical applications

Journal of Leather Science and Engineering ◽

10.1186/s42825-020-00046-9 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Yanting Han ◽

Jinlian Hu ◽

Gang Sun

Keyword(s):

Smart Materials ◽

High Performance ◽

Preparation Method ◽

Chemical Reactivity ◽

Medical Field ◽

Recent Advances ◽

Synthetic Materials ◽

Skin Collagen ◽

Promising Area ◽

Living Organisms

Abstract During nature evolution process, living organisms have gradually adapted to the environment and been adept in synthesizing high performance structural materials at mild conditions by using fairly simple building elements. The skin, as the largest organ of animals, is such a representative example. Conferred by its intricate organization where collagen fibers are arranged in a randomly interwoven network, skin collagen (SC), defined as a biomass derived from skin by removing non-collagen components displays remarkable performance with combinations of mechanical properties, chemical-reactivity and biocompatibility, which far surpasses those of synthetic materials. At present, the application of SC in medical field has been largely studied, and there have been many reviews summarizing these efforts. However, the generalized view on the aspects of SC as smart materials in non-medical fields is still lacking, although SC has shown great potential in terms of its intrinsic properties and functionality. Hence, this review will provide a comprehensive summary that integrated the recent advances in SC, including its preparation method, structure, reactivity, and functionality, as well as applications, particularly in the promising area of smart materials. Graphical abstract

Download Full-text

Transmitter and ion channel profiles of neurons in the primate abducens and trochlear nuclei

Brain Structure and Function ◽

10.1007/s00429-021-02315-7 ◽

2021 ◽

Author(s):

Ümit Suat Mayadali ◽

Jérome Fleuriet ◽

Michael Mustari ◽

Hans Straka ◽

Anja Kerstin Ellen Horn

Keyword(s):

Eye Movements ◽

Ion Channel ◽

Membrane Properties ◽

Receptor Subtype ◽

Receptor Subtypes ◽

Voltage Gated ◽

Calcium Ion Channels ◽

Cell Type Specific ◽

Transmitter Receptors ◽

Intrinsic Membrane Properties

AbstractExtraocular motoneurons initiate dynamically different eye movements, including saccades, smooth pursuit and vestibulo-ocular reflexes. These motoneurons subdivide into two main types based on the structure of the neuro-muscular interface: motoneurons of singly-innervated (SIF), and motoneurons of multiply-innervated muscle fibers (MIF). SIF motoneurons are thought to provoke strong and brief/fast muscle contractions, whereas MIF motoneurons initiate prolonged, slow contractions. While relevant for adequate functionality, transmitter and ion channel profiles associated with the morpho-physiological differences between these motoneuron types, have not been elucidated so far. This prompted us to investigate the expression of voltage-gated potassium, sodium and calcium ion channels (Kv1.1, Kv3.1b, Nav1.6, Cav3.1–3.3, KCC2), the transmitter profiles of their presynaptic terminals (vGlut1 and 2, GlyT2 and GAD) and transmitter receptors (GluR2/3, NMDAR1, GlyR1α) using immunohistochemical analyses of abducens and trochlear motoneurons and of abducens internuclear neurons (INTs) in macaque monkeys. The main findings were: (1) MIF and SIF motoneurons express unique voltage-gated ion channel profiles, respectively, likely accounting for differences in intrinsic membrane properties. (2) Presynaptic glutamatergic synapses utilize vGlut2, but not vGlut1. (3) Trochlear motoneurons receive GABAergic inputs, abducens neurons receive both GABAergic and glycinergic inputs. (4) Synaptic densities differ between MIF and SIF motoneurons, with MIF motoneurons receiving fewer terminals. (5) Glutamatergic receptor subtypes differ between MIF and SIF motoneurons. While NMDAR1 is intensely expressed in INTs, MIF motoneurons lack this receptor subtype entirely. The obtained cell-type-specific transmitter and conductance profiles illuminate the structural substrates responsible for differential contributions of neurons in the abducens and trochlear nuclei to eye movements.

Download Full-text

Identification of cell-type-specific promoters within the brain using lentiviral vectors

Gene Therapy ◽

10.1038/sj.gt.3302898 ◽

2007 ◽

Vol 14 (7) ◽

pp. 575-583 ◽

Cited By ~ 22

Author(s):

J P Chhatwal ◽

S E Hammack ◽

A M Jasnow ◽

D G Rainnie ◽

K J Ressler

Keyword(s):

Lentiviral Vectors ◽

Cell Type ◽

Cell Type Specific ◽

The Brain

Download Full-text

Comparative analysis of CreER transgenic mice for the study of brain macrophages – a case study

10.1101/725218 ◽

2019 ◽

Author(s):

Louise Chappell-Maor ◽

Masha Kolesnikov ◽

Jonathan Grozovski ◽

Jung-Seok Kim ◽

Anat Shemer ◽

...

Keyword(s):

Transgenic Mice ◽

Cre Recombinase ◽

Brain Macrophages ◽

Technological Advances ◽

Communication Circuits ◽

Cell Type Specific ◽

Definition Of ◽

The Brain ◽

Brain Macrophage

AbstractConditional mutagenesis and fate mapping have contributed considerably to our understanding of physiology and pathology. Specifically, Cre recombinase-based approaches allow the definition of cell type-specific contributions to disease development and inter-cellular communication circuits in respective animals models. Here we compared Cx3cr1CreER and Sall1CreER transgenic mice and their use to decipher the brain macrophage compartment as a showcase to discuss recent technological advances. Specifically, we highlight the need to define the accuracy of Cre recombinase expression, as well as strengths and pitfalls of these particular systems that should be taken into consideration when applying these models.

Download Full-text

Aspartoacylase Supports Oxidative Energy Metabolism during Myelination

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2012.66 ◽

2012 ◽

Vol 32 (9) ◽

pp. 1725-1736 ◽

Cited By ~ 24

Author(s):

Jeremy S Francis ◽

Louise Strande ◽

Vladamir Markov ◽

Paola Leone

Keyword(s):

Energy Metabolism ◽

Postnatal Development ◽

Strong Association ◽

Canavan Disease ◽

Lipid Synthesis ◽

Systematic Analysis ◽

Early Postnatal Development ◽

Neuronal Viability ◽

Oxidative Energy Metabolism ◽

The Brain

The inherited leukodystrophy Canavan disease arises due to a loss of the ability to catabolize N-acetylaspartic acid (NAA) in the brain and constitutes a major point of focus for efforts to define NAA function. Accumulation of noncatabolized NAA is diagnostic for Canavan disease, but contrasts with the abnormally low NAA associated with compromised neuronal integrity in a broad spectrum of other clinical conditions. Experimental evidence for NAA function supports a role in white matter lipid synthesis, but does not explain how both elevated and lowered NAA can be associated with pathology in the brain. We have undertaken a systematic analysis of postnatal development in a mouse model of Canavan disease that delineates development and pathology by identifying markers of oxidative stress preceding oligodendrocyte loss and dysmyelination. These data suggest a role for NAA in the maintenance of metabolic integrity in oligodendrocytes that may be of relevance to the strong association between NAA and neuronal viability. N-acetylaspartic acid is proposed here to support lipid synthesis and energy metabolism via the provision of substrate for both cellular processes during early postnatal development.

Download Full-text

Neuronal cell-type-specific alternative splicing: A mechanism for specifying connections in the brain?

Neurogenesis ◽

10.1080/23262133.2015.1122699 ◽

2015 ◽

Vol 2 (1) ◽

pp. e1122699 ◽

Cited By ~ 2

Author(s):

Joshua Shing Shun Li ◽

Grace Ji-eun Shin ◽

S Sean Millard

Keyword(s):

Alternative Splicing ◽

Neuronal Cell ◽

Cell Type ◽

Specific Alternative ◽

Cell Type Specific ◽

The Brain

Download Full-text

The Expanding Cell Diversity of the Brain Vasculature

Frontiers in Physiology ◽

10.3389/fphys.2020.600767 ◽

2020 ◽

Vol 11 ◽

Author(s):

Jayden M. Ross ◽

Chang Kim ◽

Denise Allen ◽

Elizabeth E. Crouch ◽

Kazim Narsinh ◽

...

Keyword(s):

Regional Blood Flow ◽

Cell Types ◽

Brain Health ◽

Vascular Cell ◽

Brain Vasculature ◽

Genomic Technologies ◽

Cell Diversity ◽

Cell Type Specific ◽

Neurologic Function ◽

The Brain

The cerebrovasculature is essential to brain health and is tasked with ensuring adequate delivery of oxygen and metabolic precursors to ensure normal neurologic function. This is coordinated through a dynamic, multi-directional cellular interplay between vascular, neuronal, and glial cells. Molecular exchanges across the blood–brain barrier or the close matching of regional blood flow with brain activation are not uniformly assigned to arteries, capillaries, and veins. Evidence has supported functional segmentation of the brain vasculature. This is achieved in part through morphologic or transcriptional heterogeneity of brain vascular cells—including endothelium, pericytes, and vascular smooth muscle. Advances with single cell genomic technologies have shown increasing cell complexity of the brain vasculature identifying previously unknown cell types and further subclassifying transcriptional diversity in cardinal vascular cell types. Cell-type specific molecular transitions or zonations have been identified. In this review, we summarize emerging evidence for the expanding vascular cell diversity in the brain and how this may provide a cellular basis for functional segmentation along the arterial-venous axis.

Download Full-text

Distinct Electrophysiological Properties in Subtypes of Nonspiking Olfactory Local Interneurons Correlate With Their Cell Type–Specific Ca2+ Current Profiles

Journal of Neurophysiology ◽

10.1152/jn.00627.2009 ◽

2009 ◽

Vol 102 (5) ◽

pp. 2834-2845 ◽

Cited By ~ 24

Author(s):

Andreas Husch ◽

Moritz Paehler ◽

Debora Fusca ◽

Lars Paeger ◽

Peter Kloppenburg

Keyword(s):

Periplaneta Americana ◽

Membrane Properties ◽

Type Ii ◽

Diverse Population ◽

Cell Type ◽

Cellular Mechanisms ◽

Electrophysiological Properties ◽

Local Interneurons ◽

Cell Type Specific ◽

Process Structure

A diverse population of local interneurons (LNs) helps to process, structure, and spatially represent olfactory information in the insect antennal lobe. In Periplaneta americana, we identified two subtypes of nonspiking local interneurons (type II LNs) by their distinct morphological and intrinsic electrophysiological properties. As an important step toward a better understanding of the cellular mechanisms that mediate odor information processing, we present a detailed analysis of their distinct voltage-activated Ca2+ currents, which clearly correlated with their distinct intrinsic electrophysiological properties. Both type II LNs did not posses voltage-activated Na+ currents and apparently innervated all glomeruli including the macroglomerulus. Type IIa LNs had significant longer and thicker low-order neurites and innervated each glomerulus entirely and homogeneously, whereas type IIb LNs innervated only parts of each glomerulus. All type II LNs were broadly tuned and responded to odorants of many chemical classes with graded changes in the membrane potential. Type IIa LNs responded with odor-specific elaborate patterns of excitation that could also include “spikelets” riding on the depolarizations and periods of inhibition. In contrast, type IIb LNs responded mostly with sustained, relatively smooth depolarizations. Consistent with the strong active membrane properties of type IIa LNs versus type IIb LNs, the voltage-activated Ca2+ current of type IIa LNs activated at more hyperpolarized membrane potentials and had a larger transient component.

Download Full-text