Three-dimensional chromatin organization in brain function and dysfunction

The three-dimensional (3D) organization of chromatin within the nucleus is now recognized as a bona fide epigenetic property influencing genome function, replication, and maintenance. In the recent years, several studies have revealed how 3D chromatin organization is associated with brain function and its emerging role in disorders of the brain. 3D chromatin organization plays a crucial role in the development of different cell types of the nervous system and some neuronal cell types have adapted unique modifications to this organization that deviates from all other cell types. In post-mitotic neurons, dynamic changes in chromatin interactions in response to neuronal activity underlie learning and memory formation. Finally, new evidence directly links 3D chromatin organization to several disorders of the brain. These recent findings position 3D chromatin organization as a fundamental regulatory mechanism poised to reveal the etiology of brain function and dysfunctions.     

TPA induces simultaneous alterations in the synthesis and organization of vimentin

We have found an increased rate of vimentin synthesis in TPA-treated chicken embryonic fibroblasts, as shown by two-dimensional electrophoretic separation of newly synthesized polypeptides. The capacity of TPA to elicit this effect correlated with its activity as a tumor promoter. Treatment with TPA also altered the organization of the vimentincontaining intermediate filaments, as revealed by immunofluorescence. Treatments which inhibited the TPA-induced rearrangements of vimentin filaments did not prevent the increase in the rate of vimentin synthesis, indicating that gross alterations in cytoskeletal organization were not the immediate cause of the altered vimentin synthesis. On the other hand, alterations in the rate of vimentin synthesis may be a necessary, but not sufficient condition for alterations in vimentin filament organization. TPA as a positive modulator of vimentin synthesis may serve as a useful probe for an eventual understanding of the dynamics of the mechanisms that control the assembly and organization of vimentin filaments.     

Diversity concept in ecology

Hierarchy of systems organization is used as a framework in advancing methodological guidelines for posing correct questions related to ecological diversity.Diversity if defined in general terms as a property of a set of elements dependent on and determines: by the epistemological perspective. Ontological diversity, because it is indefinite, is regarded as unmeasurable.Ecological diversity — be it species, spatial, reproductive or trophic, is a particular case of diversity of matter and must be precisely defined on the studied level of system organization.Diversity measurements combining more than one level of organization are information-void, for data become irretrievable as a result of such a treatment.Hypotheses explaining diversity sources are briefly surveyed. An integrated model interrelating them is constructed as a result of some basic views on the structure of matter coupled with the empirical knowledge of involved factors. The model reflects hierarchies of systems, their dynamics, and the complexities of factors affecting diversity. The model's properties suggest that it is conceptually related to an imaginary model of organization of ecological systems. Parameters recognized as invariant components of this complexity are: habitat differentiation, ecological specialization of species, ambiental changes, and integration of this system.Finally, it is shown that the peculiar shape of the species abundances curve is a necessary consequence of stratification of the system structure, which is an intrinsic attribute of hierarchical organization.     

Chromatin Architecture in the Fly: Living without CTCF/Cohesin Loop Extrusion?

The organization of the genome into topologically associated domains (TADs) appears to be a fundamental process occurring across a wide range of eukaryote organisms, and it likely plays an important role in providing an architectural foundation for gene regulation. Initial studies emphasized the remarkable parallels between TAD organization in organisms as diverse as Drosophila and mammals. However, whereas CCCTC‐binding factor (CTCF)/cohesin loop extrusion is emerging as a key mechanism for the formation of mammalian topological domains, the genome organization in Drosophila appears to depend primarily on the partitioning of chromatin state domains. Recent work suggesting a fundamental conserved role of chromatin state in building domain architecture is discussed and insights into genome organization from recent studies in Drosophila are considered.     

Structural and functional self-organization of Photosystem II in grana thylakoids

The biogenesis of the well-ordered macromolecular protein arrangement of photosystem (PS)II and light harvesting complex (LHC)II in grana thylakoid membranes is poorly understood and elusive. In this study we examine the capability of self organization of this arrangement by comparing the PSII distribution and antenna organization in isolated untreated stacked thylakoids with restacked membranes after unstacking. The PS II distribution was deduced from freeze-fracture electron microscopy. Furthermore, changes in the antenna organization and in the oligomerization state of photosystem II were monitored by chlorophyll a fluorescence parameters and size analysis of exoplasmatic fracture face particles. Low-salt induced unstacking leads to a randomization and intermixing of the protein complexes. In contrast, macromolecular PSII arrangement as well as antenna organization in thylakoids after restacking by restoring the original solvent composition is virtually identical to stacked control membranes. This indicates that the supramolecular protein arrangement in grana thylakoids is a self-organized process.     

Fibre organization and reorganization in the retinotectal projection of Xenopus

This study concerns the retinotopic organization of the ganglion cell fibres in the visual system of the frog Xenopus laevis. HRP was used to trace the pathways taken by fibres from discrete retinal positions as they pass from the retina, along the optic nerve and into the chiasma. The ganglion cell fibres in the retina are arranged in fascicles which correspond with their circumferential positions of origin. Within the fascicles the fibres show little age-related layering and do not have a strict radial organization. As the fascicles of fibres pass into the optic nerve head there is some exchange of position resulting in some loss of the retinal circumferential organization. The poor radial organization of the fibres in the retinal fascicles persists as the fibres pass through the intraocular part of the nerve. At a position just behind the eye there is a major fibre reorganization in which fibres arising from cells of increasingly peripheral retinal locations are found to have passed into increasingly peripheral positions in the nerve. Thus, fibres from peripheral-most retina are located at the nerve perimeter, whilst fibres from central retina are located in the nerve core. It is at this point that the radial, chronotopic, ordering of the ganglion cell axons, found throughout the rest of the optic pathway, is established. This annular organization persists along the length of the nerve until a position just before the nerve enters the brain. Here, fibres from each annulus move to form layers as they pass into the optic chiasma. This change in the radial organization appears to be related to the pathway followed by all newly growing fibres, in the most superficial part of the optic tract, adjacent to the pia. Just behind the eye, where fibres become radially ordered, the circumferential organization of the projection is largely lost. Fibres from every circumferential retinal position, which are of similar radial position, are distributed within the same annulus of the nerve. At the nerve-chiasma junction where each annulus forms a single layer as it enters the optic tract, there is a further mixing of fibres from all circumferential positions. However, as the fibres pass through the chiasma some active pathway selection occurs, generating the circumferential organization of the fibres in the optic tract. Additional observations of the organization of fibres in the optic nerve of Rana pipiens confirm previous reports of a dual representation of fibres within the nerve. The difference in the organization of fibres in the optic nerve of Xenopus and Rana pipiens is discussed.     

The organization of time in biological systems

A notion of organization of time similar to the notion of organization of space in architecture has been introduced. The level and pattern of organization of time in biological systems differs from that in physical and chemical systems, which presents an independent problem. Analysis of the problem leads to a new definition of life as a process of renormalization of possibilities described by a Bayes formula. This definition leads to the notion of self-monitoring as a property of every biological system, and of complicated structure of the biological present, including the physical past and physical future. This is naturally followed by determination by far past, and, hence, memory, and determination by future, i.e. preadaptation, surpassing reflection, aim-setting etc. A direct dependence of a number of elements of a complex system on its stability has been demonstrated. The self-monitoring and organization of time can be traced at various levels of biological hierarchy from intracellular to biosphere level.     

A Crowdsourced nucleus: Understanding nuclear organization in terms of dynamically networked protein function

The spatial organization of the nucleus results in a compartmentalized structure that affects all aspects of nuclear function. This compartmentalization involves genome organization as well as the formation of nuclear bodies and plays a role in many functions, including gene regulation, genome stability, replication, and RNA processing. Here we review the recent findings associated with the spatial organization of the nucleus and reveal that a common theme for nuclear proteins is their ability to participate in a variety of functions and pathways. We consider this multiplicity of function in terms of Crowdsourcing, a recent phenomenon in the world of information technology, and suggest that this model provides a novel way to synthesize the many intersections between nuclear organization and function. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development.     

Functional analysis of slow myosin heavy chain 1 and myomesin-3 in sarcomere organization in zebrafish embryonic slow muscles

Myofibrillogenesis, the process of sarcomere formation, requires close interactions of sarcomeric proteins and various components of sarcomere structures. The myosin thick filaments and M-lines are two key components of the sarcomere. It has been suggested that myomesin proteins of M-lines interact with myosin and titin proteins and keep the thick and titin filaments in order. However, the function of myomesin in myofibrillogenesis and sarcomere organization remained largely enigmatic. No knockout or knockdown animal models have been reported to elucidate the role of myomesin in sarcomere organization in vivo. In this study, by using the gene-specific knockdown approach in zebrafish embryos, we carried out a loss-of-function analysis of myomesin-3 and slow myosin heavy chain 1 (smyhc1) expressed specifically in slow muscles. We demonstrated that knockdown of smyhc1 abolished the sarcomeric localization of myomesin-3 in slow muscles. In contrast, loss of myomesin-3 had no effect on the sarcomeric organization of thick and thin filaments as well as M- and Z-line structures. Together, these studies indicate that myosin thick filaments are required for M-line organization and M-line localization of myomesin-3. In contrast, myomesin-3 is dispensable for sarcomere organization in slow muscles.     

Spatial order as a source of kinetic cooperativity in organized bound enzyme systems.

When enzyme molecules are distributed within a negatively charged matrix, the kinetics of the conversion of a negatively charged substrate into a product depends on the organization of fixed charges and bound enzyme molecules. Organization is taken to mean the existence of macroscopic heterogeneity in the distribution of fixed charge density, or of bound enzyme density, or of both. The degree of organization is quantitatively expressed by the monovariate moments of charge and enzyme distributions as well as by the bivariate moments of these two distributions. The overall reaction rate of the bound enzyme system may be expressed in terms of the monovariate moments of the charge density and of the bivariate moments of charge and enzyme densities. The monovariate moments of enzyme density do not affect the reaction rate. With respect to the situation where the fixed charges and enzyme molecules are randomly distributed in the matrix, the molecular organization, as expressed by these two types of moments, generates an increase or decrease of the overall reaction rate as well as a cooperativity of the kinetic response of the system. Thus both the alteration of the rate and the modulation of cooperativity are the consequence of a spatial organization of charges with respect to the enzyme molecules. The rate equations have been derived for different types of organization of fixed charges and enzyme molecules, namely, clustered charges and homogeneously distributed enzyme molecules, clustered enzyme molecules and homogeneously distributed charges, clusters of charges and clusters of enzymes that partly overlap, and clusters of enzymes and clusters of charges that are exactly superimposed. Computer simulations of these equations show how spatial molecular organization may modulate the overall reaction rate.     

The skin barrier in healthy and diseased state

The primary function of the skin is to protect the body for unwanted influences from the environment. The main barrier of the skin is located in the outermost layer of the skin, the stratum corneum. The stratum corneum consists of corneocytes surrounded by lipid regions. As most drugs applied onto the skin permeate along the lipid domains, the lipid organization is considered to be very important for the skin barrier function. It is for this reason that the lipid organization has been investigated quite extensively. Due to the exceptional stratum corneum lipid composition, with long chain ceramides, free fatty acids and cholesterol as main lipid classes, the lipid organization is different from that of other biological membranes. In stratum corneum, two lamellar phases are present with repeat distances of approximately 6 and 13 nm. Moreover the lipids in the lamellar phases form predominantly crystalline lateral phases, but most probably a subpopulation of lipids forms a liquid phase. Diseased skin is often characterized by a reduced barrier function and an altered lipid composition and organization. In order to understand the aberrant lipid organization in diseased skin, information on the relation between lipid composition and organization is crucial. However, due to its complexity and inter-individual variability, the use of native stratum corneum does not allow detailed systematic studies. To circumvent this problem, mixtures prepared with stratum corneum lipids can be used. In this paper first the lipid organization in stratum corneum of normal and diseased skin is described. Then the role the various lipid classes play in stratum corneum lipid organization and barrier function has been discussed. Finally, the information on the role various lipid classes play in lipid phase behavior has been used to interpret the changes in lipid organization and barrier properties of diseased skin.     

Atypical microtubule organization in undifferentiated human colon cancer cells

We previously reported that undifferentiated colonic cancer HT-29 cells, unlike the differentiated ones, exhibit unusual organelle distributions and atypical vesicle trafficking patterns, which are microtubule-independent and microfilamentdependent. In the present study, we have analyzed the microtubule network in both phenotypes, using confocal microscopy, and determined the expression levels of some rnicrotubule-associated proteins by quantitative imrnunoblotting. Differentiated cells exhibited the microtubular organization of polarized epithelial cells. Non-polarized undifferentiated cells presented an atypical microtubule organization as microtubules were localized mainly at the cell ‘top’. Immunoblot analysis indicated the absence or sow content of several structural and motor microtubule-associated proteins in undifferentiated cells, compared to differentiated cells. This may explain in part their atypical microtubular organization. This study agrees with a crucial role for microfilaments in the intracellular organization of undifferentiated HT-29 cancer cells, while differentiated HT-29 cells exhibit intracellular organization similar to that of normal enterocytic cells, although they are also tumoral.     

African Political Models in the American Southwest: Hopi as an Internal Frontier Society

Most ethnological and archeological analyses of Pueblo social organization derive its particular character from the need to adapt to an arid environment. This article challenges an ecological interpretation (without dismissing ecological constraints), finding similarities between the organization of one Pueblo society, the Hopi, and features of what Kopytoff calls "internal frontier societies" in Africa. Hopi political and ceremonial organization is viewed as responding to "internal frontier" migrations.     

Structural and functional self-organization of Photosystem II in grana thylakoids

The biogenesis of the well-ordered macromolecular protein arrangement of photosystem (PS)II and light harvesting complex (LHC)II in grana thylakoid membranes is poorly understood and elusive. In this study we examine the capability of self organization of this arrangement by comparing the PSII distribution and antenna organization in isolated untreated stacked thylakoids with restacked membranes after unstacking. The PS II distribution was deduced from freeze-fracture electron microscopy. Furthermore, changes in the antenna organization and in the oligomerization state of photosystem II were monitored by chlorophyll a fluorescence parameters and size analysis of exoplasmatic fracture face particles. Low-salt induced unstacking leads to a randomization and intermixing of the protein complexes. In contrast, macromolecular PSII arrangement as well as antenna organization in thylakoids after restacking by restoring the original solvent composition is virtually identical to stacked control membranes. This indicates that the supramolecular protein arrangement in grana thylakoids is a self-organized process.     

Interplay between genome organization and epigenomic alterations of pericentromeric DNA in cancer

In eukaryotic genome biology, the genomic organization inside the three-dimensional(3 D) nucleus is highly complex, and whether this organization governs gene expression is poorly understood. Nuclear lamina(NL)is a filamentous meshwork of proteins present at the lining of inner nuclear membrane that serves as an anchoring platform for genome organization. Large chromatin domains termed as lamina-associated domains(LADs), play a major role in silencing genes at the nuclear periphery. The interaction of the NL and genome is dynamic and stochastic. Furthermore, many genes change their positions during developmental processes or under disease conditions such as cancer, to activate certain sorts of genes and/or silence others. Pericentromeric heterochromatin(PCH) is mostly in the silenced region within the genome, which localizes at the nuclear periphery. Studies show that several genes located at the PCH are aberrantly expressed in cancer. The interesting question is that despite being localized in the pericentromeric region,how these genes still manage to overcome pericentromeric repression. Although epigenetic mechanisms control the expression of the pericentromeric region, recent studies about genome organization and genome-nuclear lamina interaction have shed light on a new aspect of pericentromeric gene regulation through a complex and coordinated interplay between epigenomic remodeling and genomic organization in cancer.     

SM22α在细胞骨架组构及血管重塑中的作用

血管平滑肌细胞（VSMC）表型转化是动脉粥样硬化、高血压和血管成形术后再狭窄等血管重塑性疾病的共同病理生理过程。VSMC表型转化过程中平滑肌特异基因的表达变化和细胞骨架的组构是当前研究的热点问题之一。平滑肌22α（SM22α）是近年发现的一种VSMC分化标志物,其表达具有平滑肌组织特异性和细胞表型特异性,该蛋白作为一种肌动蛋白细胞骨架相关蛋白参与VSMC骨架组构和收缩调节。本文就SM22α的结构特征及其在VSMC骨架组构和血管重塑中的作用机制进行综述。