Progress in molecular and subcellular biology最新文献

The chromosome biology field at large has benefited from studies of the cell cycle components, protein cascades and genomic landscape that are required for centromere identity, assembly and stable transgenerational inheritance. Research over the past 20 years has challenged the classical descriptions of a centromere as a stable, unmutable, and transcriptionally silent chromosome component. Instead, based on studies from a broad range of eukaryotic species, including yeast, fungi, plants, and animals, the centromere has been redefined as one of the more dynamic areas of the eukaryotic genome, requiring coordination of protein complex assembly, chromatin assembly, and transcriptional activity in a cell cycle specific manner. What has emerged from more recent studies is the realization that the transcription of specific types of nucleic acids is a key process in defining centromere integrity and function. To illustrate the transcriptional landscape of centromeres across eukaryotes, we focus this review on how transcripts interact with centromere proteins, when in the cell cycle centromeric transcription occurs, and what types of sequences are being transcribed. Utilizing data from broadly different organisms, a picture emerges that places centromeric transcription as an integral component of centromere function.

In recent years, considerable progress has been achieved towards the development of customized scaffold materials, in particular for bone tissue engineering and repair, by the introduction of rapid prototyping or solid freeform fabrication techniques. These new fabrication techniques allow to overcome many problems associated with conventional bone implants, such as inadequate external morphology and internal architecture, porosity and interconnectivity, and low reproducibility. However, the applicability of these new techniques is still hampered by the fact that high processing temperature or a postsintering is often required to increase the mechanical stability of the generated scaffold, as well as a post-processing, i.e., surface modification/functionalization to enhance the biocompatibility of the scaffold or to bind some bioactive component. A solution might be provided by the introduction of novel inorganic biopolymers, biosilica and polyphosphate, which resist harsh conditions applied in the RP chain and are morphogenetically active and do not need supplementation by growth factors/cytokines to stimulate the growth and the differentiation of bone-forming cells.

Biosilicification occurs in many organisms. Sponges and diatoms are major examples of them. In this chapter, we introduce a modeling approach that describes several biological mechanisms controlling silicification. Modeling biosilicification is a typical multiscale problem where processes at very different temporal and spatial scales need to be coupled: processes at the molecular level, physiological processes at the subcellular and cellular level, etc. In biosilicification morphology plays a fundamental role, and a spatiotemporal model is required. In the case of sponges, a particle simulation based on diffusion-limited aggregation is presented here. This model can describe fractal properties of silica aggregates in first steps of deposition on an organic template. In the case of diatoms, a reaction-diffusion model is introduced which can describe the concentrations of chemical components and has the possibility to include polymerization chain of reactions.

Inorganic polyphosphate (polyP) is a widely occurring but only rarely investigated biopolymer which exists in both prokaryotic and eukaryotic organisms. Only in the last few years, this polymer has been identified to cause morphogenetic activity on cells involved in human bone formation. The calcium complex of polyP was found to display a dual effect on bone-forming osteoblasts and bone-resorbing osteoclasts. Exposure of these cells to polyP (Ca(2+) complex) elicits the expression of cytokines that promote the mineralization process by osteoblasts and suppress the differentiation of osteoclast precursor cells to the functionally active mature osteoclasts dissolving bone minerals. The effect of polyP on bone formation is associated with an increased release of the bone morphogenetic protein 2 (BMP-2), a key mediator that activates the anabolic processes leading to bone formation. In addition, polyP has been shown to act as a hemostatic regulator that displays various effects on blood coagulation and fibrinolysis and might play an important role in platelet-dependent proinflammatory and procoagulant disorders.

The interaction between mineral structures and living beings is increasingly attracting the interest of research. The formation of skeletons, geomicrobiology, the study of the origin of life, soil biology, benthos biology, human and mammalian diseases generated by the inhalation of dust and biomaterials are some examples of scientific areas where the topic has a relevance. In this chapter we focus on cell reactivity to siliceous rocks and to the various forms of silicon dioxide, in particular. The examples here reported carefully review how such minerals may strongly affect different living beings, from simple ones to humans. The biomineralogy concept is explained, focusing on the effects of rocks on cell growth and development. The toxic action of silicon dioxide in mammalian lungs is the oldest evidence of crystalline silica bioactivity. More recently, we could demonstrate that crystalline silica has a deep impact on cell biology throughout the whole animal kingdom. One of the most illustrative case studies is the marine sponge Chondrosia reniformis, which has the amazing ability to incorporate and etch crystalline silica releasing dissolved silicates in the medium. This specific and selective action is due to the chemical reaction of ascorbic acid with quartz surfaces. One consequence of this is an increased production of collagen. The discovery of this mechanism opened the door to a new understanding of silica toxicity for animal cells and mammalian cells in particular. The presence of silica in sea water and substrates also affects processes like the settlement of larvae and the growth of diatoms. The following sections review all such aspects.

Polyoxometalates (PMs) as discrete metal-oxide cluster anions with high solubility in water and photochemically and electrochemically active property have a wide variety of structures not only in molecular size from sub-nano to sub-micrometers with a various combination of metals but also in symmetry and highly negative charge. One of the reasons for such a structural variety originates from their conformation change (due to the condensed aggregation and the structural assembly) which strongly depends on environmental parameters such as solution pH, concentration, and coexistent foreign inorganic and/or organic substances. In the course of the application of the physicochemical properties of such PMs to the medical fields, antitumoral, antiviral, and antibacterial activities have been developed for realization of a novel inorganic medicine which provides a biologically excellent activity never replaced by other approved medicines. Several PMs as a candidate for clinical uses have been licensed toward the chemotherapy of solid tumors (such as human gastric cancer and pancreatic cancer), DNA and RNA viruses (such as HSV, HIV, influenza, and SARS), and drug-resistant bacteria (such as MRSA and VRSA) in recent years: [NH3Pr(i)]6[Mo7O24]∙3H2O (PM-8) and [Me3NH]6[H2Mo(V) 12O28(OH)12(Mo(VI)O3)4]∙2H2O (PM-17) for solid tumors; K7[PTi2W10O40]∙6H2O (PM-19), [Pr(i)NH3]6H[PTi2W10O38(O2)2]∙H2O (PM-523), and K11H[(VO)3(SbW9O33)2]∙27H2O (PM-1002) for viruses; and K6[P2W18O62]∙14H2O (PM-27), K4[SiMo12O40]∙3H2O (SiMo12), and PM-19 for MRSA and VRSA. The results are discussed from a point of view of the chemotherapeutic clarification in this review.

Inorganic polyphosphate (PolyP) is a linear polymer containing a few to several hundred orthophosphate residues linked by energy-rich phosphoanhydride bonds. Investigation of PolyP-metabolizing enzymes is important for medicine, because PolyPs perform numerous functions in the cells. In human organism, PolyPs are involved in the regulation of Ca(2+) uptake in mitochondria, bone tissue development, and blood coagulation. The essentiality of polyphosphate kinases in the virulence of pathogenic bacteria is a basis for the discovery of new antibiotics. The properties of the major enzymes of PolyP metabolism, first of all polyphosphate kinases and exopolyphosphatases, are described in the review. The main differences between the enzymes of PolyP biosynthesis and utilization of prokaryotic and eukaryotic cells, as well as the multiple functions of some enzymes of PolyP metabolism, are considered.

Composite materials with unique architectures are ubiquitous in nature, e.g., marine shells, sponge spicules, bones, and dentine. These structured organic-inorganic systems are generated through self-assembly of organic matter (usually proteins or lipids) into scaffolds, onto which the inorganic component is deposited in organized hierarchical structures of sizes spanning several orders of magnitude. The development of bio-inspired materials is possible through the design of synthetic bottom-up self-assembly methods. Knowledge of the structure is required in order to assess the efficiency of their design and evaluate their properties. This chapter reviews the main methods used for structure determination of natural and synthetic inorganic biomaterials, namely, X-ray diffraction and scattering and electron diffraction and microscopy (TEM, SEM), as well as the AFM and CSLM microscopy methods. Moreover, spectroscopic (IR, NMR, and Raman) and thermal methods are presented. Examples of biomimetic synthetic materials are used to show the contribution of single or multiple techniques in the elucidation of their structure.

An overview of the biological activities of arsenic compounds containing more than one arsenic atom in their molecular structure is presented. This contribution covers the literature of the last 10-12 years concerning the in vitro and in vivo studies on arsenic species. They include inorganic oxides and sulfides, already employed for a long time in traditional Chinese medicine and currently investigated against hematological or solid malignancies, with arsenic trioxide clinically used in the treatment of acute promyelocytic leukemia. Chemical and biological aspects on the marine product arsenicin A, representing the first and only organic polyarsenical isolated from Nature, have also been reviewed, pointing out the characterization of its C3H6As4O3 molecular structure by experimental and theoretical vibrational spectroscopies, the potent antimicrobial activities, and the promising perspectives as an antitumor agent.

Vanadate is widely used as an inhibitor of protein tyrosine phosphatases (PTPase) and is routinely applied in cell lysis buffers or immunoprecipitations of phosphotyrosyl proteins. Additionally, vanadate has been extensively studied for its antidiabetic and anticancer effects. In most studies, orthovanadate or metavanadate was used as the starting compound, whereas these "vanadate" solutions may contain more or less oligomerized species. Whether and how different species of vanadium compounds formed in the biological media exert specific biological effect is still a mystery. In the present commentary, we focus on the chemical, biochemical, and biological behaviors of vanadate. On the basis of species formation of vanadate in chemical and biological systems, we compared the biological effects and working mechanism of monovanadate with that of its oligomers, especially the decamer. We propose that different oligomers may exert a specific biological effect, which depends on their structures and the context of the cell types, by different modes of action.