scholarly journals Cubic membranes: a legend beyond the Flatland* of cell membrane organization

2006 ◽  
Vol 173 (6) ◽  
pp. 839-844 ◽  
Author(s):  
Zakaria A. Almsherqi ◽  
Sepp D. Kohlwein ◽  
Yuru Deng
Keyword(s):  
Smooth Endoplasmic Reticulum ◽  
Three Dimensional ◽  
Cell Types ◽  
Membrane Morphology ◽  
Triply Periodic ◽  
Numerous Cell ◽  
Infected Cells ◽  
And Function ◽  
First Time ◽  
Cubic Membrane

Cubic membranes represent highly curved, three-dimensional nanoperiodic structures that correspond to mathematically well defined triply periodic minimal surfaces. Although they have been observed in numerous cell types and under different conditions, particularly in stressed, diseased, or virally infected cells, knowledge about the formation and function of nonlamellar, cubic structures in biological systems is scarce, and research so far is restricted to the descriptive level. We show that the “organized smooth endoplasmic reticulum” (OSER; Snapp, E.L., R.S. Hegde, M. Francolini, F. Lombardo, S. Colombo, E. Pedrazzini, N. Borgese, and J. Lippincott-Schwartz. 2003. J. Cell Biol. 163:257–269), which is formed in response to elevated levels of specific membrane-resident proteins, is actually the two-dimensional representation of two subtypes of cubic membrane morphology. Controlled OSER induction may thus provide, for the first time, a valuable tool to study cubic membrane formation and function at the molecular level.

scholarly journals Developmental enhancers and chromosome topology

Science ◽  
2018 ◽  
Vol 361 (6409) ◽  
pp. 1341-1345 ◽  
Author(s):  
Eileen E. M. Furlong ◽  
Michael Levine
Keyword(s):  
Three Dimensional ◽  
Cell Types ◽  
Living Cells ◽  
Specific Cell ◽  
Transcriptional Dynamics ◽  
Spatiotemporal Expression ◽  
Chromosome Topology ◽  
Classical Models ◽  
And Function ◽  
Target Promoters

Developmental enhancers mediate on/off patterns of gene expression in specific cell types at particular stages during metazoan embryogenesis. They typically integrate multiple signals and regulatory determinants to achieve precise spatiotemporal expression. Such enhancers can map quite far—one megabase or more—from the genes they regulate. How remote enhancers relay regulatory information to their target promoters is one of the central mysteries of genome organization and function. A variety of contrasting mechanisms have been proposed over the years, including enhancer tracking, linking, looping, and mobilization to transcription factories. We argue that extreme versions of these mechanisms cannot account for the transcriptional dynamics and precision seen in living cells, tissues, and embryos. We describe emerging evidence for dynamic three-dimensional hubs that combine different elements of the classical models.

scholarly journals Actin-binding compounds, previously discovered by FRET-based high-throughput screening, differentially affect skeletal and cardiac muscle

2020 ◽  
Vol 295 (41) ◽  
pp. 14100-14110 ◽  
Author(s):  
Piyali Guhathakurta ◽  
Lien A. Phung ◽  
Ewa Prochniewicz ◽  
Sarah Lichtenberger ◽  
Anna Wilson ◽  
...  
Keyword(s):  
Cardiac Muscle ◽  
High Throughput ◽  
High Throughput Screening ◽  
Cell Types ◽  
Actin Binding ◽  
Time Resolved ◽  
Biochemical Assays ◽  
Numerous Cell ◽  
Cardiac Muscles ◽  
And Function

Actin's interactions with myosin and other actin-binding proteins are essential for cellular viability in numerous cell types, including muscle. In a previous high-throughput time-resolved FRET (TR-FRET) screen, we identified a class of compounds that bind to actin and affect actomyosin structure and function. For clinical utility, it is highly desirable to identify compounds that affect skeletal and cardiac muscle differently. Because actin is more highly conserved than myosin and most other muscle proteins, most such efforts have not targeted actin. Nevertheless, in the current study, we tested the specificity of the previously discovered actin-binding compounds for effects on skeletal and cardiac α-actins as well as on skeletal and cardiac myofibrils. We found that a majority of these compounds affected the transition of monomeric G-actin to filamentous F-actin, and that several of these effects were different for skeletal and cardiac actin isoforms. We also found that several of these compounds affected ATPase activity differently in skeletal and cardiac myofibrils. We conclude that these structural and biochemical assays can be used to identify actin-binding compounds that differentially affect skeletal and cardiac muscles. The results of this study set the stage for screening of large chemical libraries for discovery of novel compounds that act therapeutically and specifically on cardiac or skeletal muscle.

scholarly journals Immunomodulation by Gut Microbiota: Role of Toll-Like Receptor Expressed by T Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Mariagrazia Valentini ◽  
Alessia Piermattei ◽  
Gabriele Di Sante ◽  
Giuseppe Migliara ◽  
Giovanni Delogu ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Gut Microbiota ◽  
Cell Types ◽  
Mutual Regulation ◽  
Close Relationship ◽  
Numerous Cell ◽  
Specific Receptors ◽  
And Function

A close relationship exists between gut microbiota and immune responses. An imbalance of this relationship can determine local and systemic immune diseases. In fact the immune system plays an essential role in maintaining the homeostasis with the microbiota that normally resides in the gut, while, at the same time, the gut microbiota influences the immune system, modulating number and function of effector and regulatory T cells. To achieve this aim, mutual regulation between immune system and microbiota is achieved through several mechanisms, including the engagement of toll-like receptors (TLRs), pathogen-specific receptors expressed on numerous cell types. TLRs are able to recognize ligands from commensal or pathogen microbiota to maintain the tolerance or trigger the immune response. In this review, we summarize the latest evidences about the role of TLRs expressed in adaptive T cells, to understand how the immune system promotes intestinal homeostasis, fights invasion by pathogens, and is modulated by the intestinal microbiota.

scholarly journals A Dedifferentiation Strategy to Enhance the Osteogenic Potential of Dental Derived Stem Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Francesco Paduano ◽  
Elisabetta Aiello ◽  
Paul Roy Cooper ◽  
Benedetta Marrelli ◽  
Irina Makeeva ◽  
...  
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Cell Fate ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Osteogenic Potential ◽  
Alternative Source ◽  
Dental Tissues ◽  
Numerous Cell ◽  
First Time

Dental stem cells (DSCs) holds the ability to differentiate into numerous cell types. This property makes these cells particularly appropriate for therapeutic use in regenerative medicine. We report evidence that when DSCs undergo osteogenic differentiation, the osteoblast-like cells can be reverted back to a stem-like state and then further differentiated toward the osteogenic phenotype again, without gene manipulation. We have investigated two different MSCs types, both from dental tissues: dental follicle progenitor stem cells (DFPCs) and dental pulp stem cells (DPSCs). After osteogenic differentiation, both DFPCs and DPSCs can be reverted to a naïve stem cell-like status; importantly, dedifferentiated DSCs showed a greater potential to further differentiate toward the osteogenic phenotype. Our report aims to demonstrate for the first time that it is possible, under physiological conditions, to control the dedifferentiation of DSCs and that the rerouting of cell fate could potentially be used to enhance their osteogenic therapeutic potential. Significantly, this study first validates the use of dedifferentiated DSCs as an alternative source for bone tissue engineering.

scholarly journals IMGT® and 30 Years of Immunoinformatics Insight in Antibody V and C Domain Structure and Function

Antibodies ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 29 ◽  
Author(s):  
Lefranc ◽  
Lefranc
Keyword(s):  
Domain Structure ◽  
High Throughput Sequencing ◽  
Genome Mapping ◽  
Three Dimensional ◽  
Cell Receptor ◽  
Structure And Function ◽  
Antibody Engineering ◽  
New Science ◽  
And Function ◽  
First Time

At the 10th Human Genome Mapping (HGM10) Workshop, in New Haven, for the first time, immunoglobulin (IG) or antibody and T cell receptor (TR) variable (V), diversity (D), joining (J), and constant (C) genes were officially recognized as ‘genes’, as were the conventional genes. Under these HGM auspices, IMGT®, the international ImMunoGeneTics information system® (http://www.imgt.org), was created in June 1989 at Montpellier (University of Montpellier and CNRS). The creation of IMGT® marked the birth of immunoinformatics, a new science, at the interface between immunogenetics and bioinformatics. The accuracy and the consistency between genes and alleles, sequences, and three-dimensional (3D) structures are based on the IMGT Scientific chart rules generated from the IMGT-ONTOLOGY axioms and concepts: IMGT standardized keywords (IDENTIFICATION), IMGT gene and allele nomenclature (CLASSIFICATION), IMGT standardized labels (DESCRIPTION), IMGT unique numbering and IMGT Collier de Perles (NUMEROTATION). These concepts provide IMGT® immunoinformatics insights for antibody V and C domain structure and function, used for the standardized description in IMGT® web resources, databases and tools, immune repertoires analysis, single cell and/or high-throughput sequencing (HTS, NGS), antibody humanization, and antibody engineering in relation with effector properties.

Mathematical modelling of the viable epidermis: impact of cell shape and vertical arrangement

2017 ◽  
Vol 25 (5) ◽  
pp. 1046-1059 ◽  
Author(s):  
Rebecca Wittum ◽  
Arne Naegel ◽  
Michael Heisig ◽  
Gabriel Wittum
Keyword(s):  
Mathematical Modelling ◽  
Cell Shape ◽  
Vertical Direction ◽  
Cell Types ◽  
Stratum Granulosum ◽  
Viable Epidermis ◽  
Membrane Permeabilities ◽  
And Function ◽  
First Time ◽  
In Silico Methods

In-silico methods are valuable tools for understanding the barrier function of the skin. The key benefit is that mathematical modelling allows the interplay between cell shape and function to be elucidated. This study focuses on the viable (living) epidermis. For this region, previous works suggested a diffusion model and an approximation of the cells by hexagonal prisms. The work at hand extends this in three ways. First, the extracellular space is treated with full spatial resolution. This induces a decrease of permeability by about 10%. Second, cells of tetrakaidecahedral shape are considered, in addition to the original hexagonal prisms. For both cell types, the resulting membrane permeabilities are compared. Third, for the first time, the influence of cell stacking in the vertical direction is considered. This is particularly important for the stratum granulosum, where tight junctions are present.

scholarly journals Cubic membranes: a structure-based design for DNA uptake

2008 ◽  
Vol 5 (26) ◽  
pp. 1023-1029 ◽  
Author(s):  
Zakaria Almsherqi ◽  
Stephen Hyde ◽  
Malarmathy Ramachandran ◽  
Yuru Deng
Keyword(s):  
Mammalian Cells ◽  
Gene Transfection ◽  
Three Dimensional ◽  
Microscopic Analysis ◽  
Cell Types ◽  
Dna Uptake ◽  
Cell Organelles ◽  
Electron Microscopic ◽  
Culture Cells ◽  
Cubic Membrane

Cubic membranes are soft three-dimensional crystals found within cell organelles in a variety of living systems, despite the aphorism of Fedorov: ‘crystallization is death’. They consist of multi-bilayer lipid–protein stacks, folded onto anticlastic surfaces that resemble triply periodic minimal surfaces, forming highly swollen crystalline sponges. Although cubic membranes have been observed in numerous cell types and under different pathophysiological conditions, knowledge about the formation and potential function(s) of non-lamellar, cubic structures in biological systems is scarce. We report that mitochondria with this cubic membrane organization isolated from starved amoeba Chaos carolinense interact sufficiently with short segments of phosphorothioate oligonucleotides (PS-ODNs) to give significant ODNs uptake. ODNs condensed within the convoluted channels of cubic membrane by an unknown passive targeting mechanism. Moreover, the interaction between ODNs and cubic membrane is sufficient to retard electrophoretic mobility of the ODN component in the gel matrix. These ODN–cubic membrane complexes are readily internalized within the cytoplasm of cultured mammalian cells. Transmission electron microscopic analysis confirms ODNs uptake by cubic membranes and internalization of ODN–cubic membrane complexes into the culture cells. Cubic membranes thus may offer a new, potentially benign medium for gene transfection.

scholarly journals Retrotransposons as Drivers of Mammalian Brain Evolution

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 376
Author(s):  
Roberto Ferrari ◽  
Nicole Grandi ◽  
Enzo Tramontano ◽  
Giorgio Dieci
Keyword(s):  
Cognitive Abilities ◽  
Large Scale ◽  
Transcriptional Control ◽  
Large Body ◽  
Three Dimensional ◽  
Brain Evolution ◽  
Cell Types ◽  
Brain Morphology ◽  
Mammalian Brain ◽  
And Function

Retrotransposons, a large and diverse class of transposable elements that are still active in humans, represent a remarkable force of genomic innovation underlying mammalian evolution. Among the features distinguishing mammals from all other vertebrates, the presence of a neocortex with a peculiar neuronal organization, composition and connectivity is perhaps the one that, by affecting the cognitive abilities of mammals, contributed mostly to their evolutionary success. Among mammals, hominids and especially humans display an extraordinarily expanded cortical volume, an enrichment of the repertoire of neural cell types and more elaborate patterns of neuronal connectivity. Retrotransposon-derived sequences have recently been implicated in multiple layers of gene regulation in the brain, from transcriptional and post-transcriptional control to both local and large-scale three-dimensional chromatin organization. Accordingly, an increasing variety of neurodevelopmental and neurodegenerative conditions are being recognized to be associated with retrotransposon dysregulation. We review here a large body of recent studies lending support to the idea that retrotransposon-dependent evolutionary novelties were crucial for the emergence of mammalian, primate and human peculiarities of brain morphology and function.

Three-Dimensional Assembly of Multilayered Tissues Using Water Transfer Printing

2013 ◽  
Vol 25 (4) ◽  
pp. 690-697 ◽  
Author(s):  
Taisuke Masuda ◽  
◽  
Yuka Yamagishi ◽  
Natsuki Takei ◽  
Hirofumi Owaki ◽  
...  
Keyword(s):  
Initial Conditions ◽  
Three Dimensional ◽  
In Vitro Models ◽  
Water Transfer ◽  
Transfer Printing ◽  
Numerous Cell ◽  
3D Assembly ◽  
Assembly Technique ◽  
And Function

A rapid construction process is necessary to build up numerous cell modules into three-dimensional (3D) tissues that retain the tissue geometries and initial conditions of the cells. We propose a new 3D assembly technique using water transfer printing to fabricate a hollow tubular tissue structure. Utilizing this assembly technique, we discuss the relationship between the 3D transcriptional body of a gel matrix and the developed shape of transferred tissue. We then fabricate hollow tubular tissue. Simulation of the 3D environment in which tissues normally develop and function is crucial for the engineering of in vitro models that can be used for the formation of complex tissues. These artificial hollow tubular tissues could be used as in vitro simulators for drug efficiency evaluation and operative training.

‘This strange little palaeoniscid': a new early actinopterygian genus, and commentary on pectoral fin conditions and function

2018 ◽  
Vol 109 (1-2) ◽  
pp. 15-31 ◽  
Author(s):  
Michael I. COATES ◽  
Kristen TIETJEN
Keyword(s):  
Phylogenetic Analyses ◽  
General Pattern ◽  
Three Dimensional ◽  
Leading Edge ◽  
Ct Scans ◽  
Pectoral Girdle ◽  
High Resolution Computed Tomography ◽  
Ct Data ◽  
And Function ◽  
First Time

ABSTRACTThe early actinopterygian Mesopoma planti is reassigned to a new genus on the basis of data obtained from high-resolution computed tomography (CT) scans of an unusually well-preserved specimen from the Early Pennsylvanian of Lancashire, UK. The former M. planti is joined by two further Mesopoma species from the Late Mississippian of Scotland. CT scans of the key planti specimen bring to light new details of the dermal skull, pectoral girdle and fin. Among the cranial features, CT data reveal a specialised, anteriorly projecting preopercular bone, the location of the spiracular duct opening, presence of a so-called coronoid process on the lower jaw and the full three-dimensional shape of the snout. Of the pectoral girdle and fin, for the first time in a Palaeozoic actinopterygian it has been possible to complete a three-dimensional reconstruction of the entire endoskeleton in articulation. The fin presents new diversity within a conservative general pattern, revealing for the first time a double propterygium. Girdle shape shows that the fin orientation is derived: rotated with the leading edge dorsalmost. These details are used to identify unexploited character states for use in phylogenetic analyses, while functional implications of the fin and girdle suggest advanced locomotory control emerging among different groups of post-Devonian ray-finned fishes.

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