scholarly journals Systems for intricate patterning of the vertebrate anatomy

Author(s):  
Kevin J. Painter ◽  
Mariya Ptashnyk ◽  
Denis J. Headon

Periodic patterns form intricate arrays in the vertebrate anatomy, notably the hair and feather follicles of the skin, but also internally the villi of the gut and the many branches of the lung, kidney, mammary and salivary glands. These tissues are composite structures, being composed of adjoined epithelium and mesenchyme, and the patterns that arise within them require interaction between these two tissue layers. In embryonic development, cells change both their distribution and state in a periodic manner, defining the size and relative positions of these specialized structures. Their placement is determined by simple spacing mechanisms, with substantial evidence pointing to a variety of local enhancement/lateral inhibition systems underlying the breaking of symmetry. The nature of the cellular processes involved, however, has been less clear. While much attention has focused on intercellular soluble signals, such as protein growth factors, experimental evidence has grown for contributions of cell movement or mechanical forces to symmetry breaking. In the mesenchyme, unlike the epithelium, cells may move freely and can self-organize into aggregates by chemotaxis, or through generation and response to mechanical strain on their surrounding matrix. Different modes of self-organization may coexist, either coordinated into a single system or with hierarchical relationships. Consideration of a broad range of distinct biological processes is required to advance understanding of biological pattern formation. This article is part of the theme issue 'Recent progress and open frontiers in Turing's theory of morphogenesis'.

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2118
Author(s):  
Yusuke Hosoya ◽  
Junko Ohkanda

Intrinsically disordered proteins (IDPs) are critical players in the dynamic control of diverse cellular processes, and provide potential new drug targets because their dysregulation is closely related to many diseases. This review focuses on several medicinal studies that have identified low-molecular-weight inhibitors of IDPs. In addition, clinically relevant liquid–liquid phase separations—which critically involve both intermolecular interactions between IDPs and their posttranslational modification—are analyzed to understand the potential of IDPs as new drug targets.


Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 342
Author(s):  
Lihi Gershon ◽  
Martin Kupiec

Acetylation on lysine 56 of histone H3 of the yeast Saccharomyces cerevisiae has been implicated in many cellular processes that affect genome stability. Despite being the object of much research, the complete scope of the roles played by K56 acetylation is not fully understood even today. The acetylation is put in place at the S-phase of the cell cycle, in order to flag newly synthesized histones that are incorporated during DNA replication. The signal is removed by two redundant deacetylases, Hst3 and Hst4, at the entry to G2/M phase. Its crucial location, at the entry and exit points of the DNA into and out of the nucleosome, makes this a central modification, and dictates that if acetylation and deacetylation are not well concerted and executed in a timely fashion, severe genomic instability arises. In this review, we explore the wealth of information available on the many roles played by H3K56 acetylation and the deacetylases Hst3 and Hst4 in DNA replication and repair.


Polymers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 180
Author(s):  
Kirill Minchenkov ◽  
Alexander Vedernikov ◽  
Alexander Safonov ◽  
Iskander Akhatov

Pultrusion is one of the most efficient methods of producing polymer composite structures with a constant cross-section. Pultruded profiles are widely used in bridge construction, transportation industry, energy sector, and civil and architectural engineering. However, in spite of the many advantages thermoplastic composites have over the thermoset ones, the thermoplastic pultrusion market demonstrates significantly lower production volumes as compared to those of the thermoset one. Examining the thermoplastic pultrusion processes, raw materials, mechanical properties of thermoplastic composites, process simulation techniques, patents, and applications of thermoplastic pultrusion, this overview aims to analyze the existing gap between thermoset and thermoplastic pultrusions in order to promote the development of the latter one. Therefore, observing thermoplastic pultrusion from a new perspective, we intend to identify current shortcomings and issues, and to propose future research and application directions.


Author(s):  
Lorenzo Cangiano ◽  
Sabrina Asteriti

AbstractIn the vertebrate retina, signals generated by cones of different spectral preference and by highly sensitive rod photoreceptors interact at various levels to extract salient visual information. The first opportunity for such interaction is offered by electrical coupling of the photoreceptors themselves, which is mediated by gap junctions located at the contact points of specialised cellular processes: synaptic terminals, telodendria and radial fins. Here, we examine the evolutionary pressures for and against interphotoreceptor coupling, which are likely to have shaped how coupling is deployed in different species. The impact of coupling on signal to noise ratio, spatial acuity, contrast sensitivity, absolute and increment threshold, retinal signal flow and colour discrimination is discussed while emphasising available data from a variety of vertebrate models spanning from lampreys to primates. We highlight the many gaps in our knowledge, persisting discrepancies in the literature, as well as some major unanswered questions on the actual extent and physiological role of cone-cone, rod-cone and rod-rod communication. Lastly, we point toward limited but intriguing evidence suggestive of the ancestral form of coupling among ciliary photoreceptors.


Biomolecules ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 45 ◽  
Author(s):  
Manuel Giménez-Andrés ◽  
Alenka Čopič ◽  
Bruno Antonny

Amphipathic helices (AHs), a secondary feature found in many proteins, are defined by their structure and by the segregation of hydrophobic and polar residues between two faces of the helix. This segregation allows AHs to adsorb at polar–apolar interfaces such as the lipid surfaces of cellular organelles. Using various examples, we discuss here how variations within this general scheme impart membrane-interacting AHs with different interfacial properties. Among the key parameters are: (i) the size of hydrophobic residues and their density per helical turn; (ii) the nature, the charge, and the distribution of polar residues; and (iii) the length of the AH. Depending on how these parameters are tuned, AHs can deform lipid bilayers, sense membrane curvature, recognize specific lipids, coat lipid droplets, or protect membranes from stress. Via these diverse mechanisms, AHs play important roles in many cellular processes.


2006 ◽  
Vol 26 (12) ◽  
pp. 4539-4552 ◽  
Author(s):  
Keqin Zhang ◽  
Cielo Barragan-Adjemian ◽  
Ling Ye ◽  
Shiva Kotha ◽  
Mark Dallas ◽  
...  

ABSTRACT Within mineralized bone, osteocytes form dendritic processes that travel through canaliculi to make contact with other osteocytes and cells on the bone surface. This three-dimensional syncytium is thought to be necessary to maintain viability, cell-to-cell communication, and mechanosensation. E11/gp38 is the earliest osteocyte-selective protein to be expressed as the osteoblast differentiates into an osteoid cell or osteocyte, first appearing on the forming dendritic processes of these cells. Bone extracts contain large amounts of E11, but immunostaining only shows its presence in early osteocytes compared to more deeply embedded cells, suggesting epitope masking by mineral. Freshly isolated primary osteoblasts are negative for E11 expression but begin to express this protein in culture, and expression increases with time, suggesting differentiation into the osteocyte phenotype. Osteoblast-like cell lines 2T3 and Oct-1 also show increased expression of E11 with differentiation and mineralization. E11 is highly expressed in MLO-Y4 osteocyte-like cells compared to osteoblast cell lines and primary osteoblasts. Differentiated, mineralized 2T3 cells and MLO-Y4 cells subjected to fluid flow shear stress show an increase in mRNA for E11. MLO-Y4 cells show an increase in dendricity and elongation of dendrites in response to shear stress that is blocked by small interfering RNA specific to E11. In vivo, E11 expression is also increased by a mechanical load, not only in osteocytes near the bone surface but also in osteocytes more deeply embedded in bone. Maximal expression is observed not in regions of maximal strain but in a region of potential bone remodeling, suggesting that dendrite elongation may be occurring during this process. These data suggest that osteocytes may be able to extend their cellular processes after embedment in mineralized matrix and have implications for osteocytic modification of their microenvironment.


2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Zibo Zhao ◽  
Ali Shilatifard

AbstractThe epigenetic modifications of histones are versatile marks that are intimately connected to development and disease pathogenesis including human cancers. In this review, we will discuss the many different types of histone modifications and the biological processes with which they are involved. Specifically, we review the enzymatic machineries and modifications that are involved in cancer development and progression, and how to apply currently available small molecule inhibitors for histone modifiers as tool compounds to study the functional significance of histone modifications and their clinical implications.


Author(s):  
Kyungsuk Yum ◽  
Sungsoo Na ◽  
Yang Xiang ◽  
Ning Wang ◽  
Min-Feng Yu

Studying biological processes and mechanics in living cells is challenging but highly rewarding. Recent advances in experimental techniques have provided numerous ways to investigate cellular processes and mechanics of living cells. However, most of existing techniques for biomechanics are limited to experiments outside or on the membrane of cells, due to the difficulties in physically accessing the interior of living cells. On the other hand, nanomaterials, such as fluorescent quantum dots (QDs) and magnetic nanoparticles, have shown great promise to overcome such limitations due to their small sizes and excellent functionalities, including bright and stable fluorescence and remote manipulability. However, except a few systems, the use of nanoparticles has been limited to the study of biological studies on cell membranes or related to endocytosis, because of the difficulty of delivering dispersed and single nanoparticles into living cells. Various strategies have been explored, but delivered nanoparticles are often trapped in the endocytic pathway or form aggregates in the cytoplasm, limiting their further use. Here we show a nanoscale direct delivery method, named nanomechanochemical delivery, where we manipulate a nanotube-based nanoneedle, carrying “cargo” (QDs in this study), to mechanically penetrate the cell membrane, access specific areas inside cells, and release the cargo [1]. We selectively delivered well-dispersed QDs into either the cytoplasm or the nucleus of living cells. We quantified the dynamics of the delivered QDs by single-molecule tracking and demonstrated the applicability of the QDs as a nanoscale probe for studying nanomechanics inside living cells (by using the biomicrorhology method), revealing the biomechanical heterogeneity of the cellular environment. This method may allow new strategies for studying biological processes and mechanics in living cells with spatial and temporal precision, potentially at the single-molecule level.


Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1132
Author(s):  
Xiaolong Wang ◽  
Meiqian Weng ◽  
Yuting Ke ◽  
Ellen Sapp ◽  
Marian DiFiglia ◽  
...  

Coordinated actions of Rab and Rho are necessary for numerous essential cellular processes ranging from vesicle budding to whole cell movement. How Rab and Rho are choreographed is poorly understood. Here, we report a protein complex comprised of kalirin, a Rho guanine nucleotide exchange factor (GEF) activating Rac1, and RabGEF transport protein particle (TRAPP). Kalirin was identified in a mass spectrometry analysis of proteins precipitated by trappc4 and detected on membranous organelles containing trappc4. Acute knockdown of kalirin did not affect trappc4, but significantly reduced overall and membrane-bound levels of trappc9, which specifies TRAPP toward activating Rab11. Trappc9 deficiency led to elevated expression of kalirin in neurons. Co-localization of kalirin and Rab11 occurred at a low frequency in NRK cells under steady state and was enhanced upon expressing an inactive Rab11 mutant to prohibit the dissociation of Rab11 from the kalirin-TRAPP complex. The small RNA-mediated depletion of kalirin diminished activities in cellular membranes for activating Rab11 and resulted in a shift in size of Rab11 positive structures from small to larger ones and tubulation of recycling endosomes. Our study suggests that kalirin and TRAPP form a dual GEF complex to choreograph actions of Rab11 and Rac1 at recycling endosomes.


2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Fanglei Zhuang ◽  
Ryan T. Fuchs ◽  
G. Brett Robb

Eukaryotic regulatory small RNAs (sRNAs) play significant roles in many fundamental cellular processes. As such, they have emerged as useful biomarkers for diseases and cell differentiation states. sRNA-based biomarkers outperform traditional messenger RNA-based biomarkers by testing fewer targets with greater accuracy and providing earlier detection for disease states. Therefore, expression profiling of sRNAs is fundamentally important to further advance the understanding of biological processes, as well as diagnosis and treatment of diseases. High-throughput sequencing (HTS) is a powerful approach for both sRNA discovery and expression profiling. Here, we discuss the general considerations for sRNA-based HTS profiling methods from RNA preparation to sequencing library construction, with a focus on the causes of systematic error. By examining the enzymatic manipulation steps of sRNA expression profiling, this paper aims to demystify current HTS-based sRNA profiling approaches and to aid researchers in the informed design and interpretation of profiling experiments.


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