The mammalian centrosome and its functional significance

Primarily known for its role as major microtubule organizing center, the centrosome is increasingly being recognized for its functional significance in key cell cycle regulating events. We are now at the beginning of understanding the centrosome's functional complexities and its major impact on directing complex interactions and signal transduction cascades important for cell cycle regulation. The centrosome orchestrates entry into mitosis, anaphase onset, cytokinesis, G1/S transition, and monitors DNA damage. Recently, the centrosome has also been recognized as major docking station where regulatory complexes accumulate including kinases and phosphatases as well as numerous other cell cycle regulators that utilize the centrosome as platform to coordinate multiple cell cycle-specific functions. Vesicles that are translocated along microtubules to and away from centrosomes may also carry enzymes or substrates that use centrosomes as main docking station. The centrosome's role in various diseases has been recognized and a wealth of data has been accumulated linking dysfunctional centrosomes to cancer, Alstrom syndrome, various neurological disorders, and others. Centrosome abnormalities and dysfunctions have been associated with several types of infertility. The present review highlights the centrosome's significant roles in cell cycle events in somatic and reproductive cells and discusses centrosome abnormalities and implications in disease.     

植物功能型及其生态学意义

植物功能型是近年来在全球变化研究中引入的一个新的生态学术语,综 植物功能型概念的由来、划分植物及其生态学意义,用系统生物学的理论与方法理解植物功能型,并指出了植物功能型在全球变化研究中的意义。     

Conformational flexibility and its functional significance in some protein molecules

Crystallography has contributed much to our knowledge of protein flexibility and here are described some examples of large-scale segmental flexibilities discovered by X=ray diffraction. These examples indicate that flexibility may be required for enzymatic catalysis and other functions of proteins, and also for their regulation.     

Three-dimensional domain swapping in homooligomeric proteins and its functional significance

In the process of oligomeric structure formation through a mechanism of three-dimensional domain swapping, one domain of a monomeric protein is replaced by the same domain from an identical monomer. The swapped domain can represent an entire tertiary globular domain or an element of secondary protein structure, such as an -helix or a -strand. Different examples of three-dimensional domain swapping are reviewed; the functional importance of this phenomenon and its role in the development of new properties by some proteins in the process of evolution are considered. The contribution of three-dimensional domain swapping to the formation of linear protein polymers and amyloids is discussed.     

IL-17 receptor and its functional significance in psoriatic arthritis

To delineate the functional significance of IL-17 Receptor (IL-17RA) and characterize the IL-17 producing T cell (Th17) subpopulation in psoriatic arthritis (PsA). Mononuclear cells from blood and synovial fluid (SF) were obtained from PsA (n=20), rheumatoid arthritis (RA, n=20) and osteoarthritis (OA, n=20) patients. Synoviocytes (FLS) were isolated from the synovium of RA (n=5), PsA (n=5) and OA (n=5) patients. IL-17RA expression in FLS was identified by western blotting (WB) and flowcytometry. T lymphocytes derived from the SF of these patients were studied to identify and phenotype the Th17 cells. The functional significance of IL-17RA was determined by evaluating its regulatory role on the production of proinflammatory cytokines and endopeptidase. IL-17RA expression was found to be significantly higher in FLS of RA (15.7%±4.9) and PsA (4.5%±0.9) in comparison to OA (1.14%±0.9). Western blot analyses showed that the relative intensity (RI) of IL-17RA protein was higher in RA and PsA compared to OA (Fisher exact, P<0.01). A significant enrichment of IL-17-producing CD4+ T cells (7.9%±2.8) was observed in the SF of PsA patients compared to that of OA patients (P<.001). Compared to OA-FLS, recombinant IL-17 induced higher levels of IL-6, IL-8, and MMP-3 production in PsA-FLS. Blockage of IL-17RA with an anti-IL-17RA antibody inhibited the production of IL-6, IL-8, and MMP-3. This is the first report to demonstrate the functional significance of IL-17RA in PsA. Results of this study support the hypothesis that IL-17RA blocking antibodies have the potential to be a therapeutic option for psoriatic arthritis.     

Scaling of the marsupial middle ear and its functional significance

The marsupial middle ear performs an anatomical impedance matching for acoustic energy travelling in air to reach the cochlea. The size of the middle ear sets constraints for the frequencies transmitted. For generalized placental mammals, it has been shown that the limit for high-frequency hearing can be predicted on the basis of middle ear ossicle mass, provided that the ears fulfil requirements of isometry. We studied the interspecific size variation of the middle ear in 23 marsupial species, with the following measurable parameters: skull mass, condylobasal length, ossicular masses for malleus, incus and stapes, tympanic membrane area, oval window area, and lever arm lengths for malleus and incus. Our results show that the middle ear size grows with negative allometry in relation to body size and that the internal proportions of the marsupial middle ear are largely isometric. This resembles the situation in placental mammals and allows us to use their isometric middle ear model to predict the high-frequency hearing limit for marsupials. We found that the isometry model predicts the high-frequency hearing limit for different marsupials well, indicating that marsupials can be used as auditory models for general therian mammalian hearing. At very high frequencies, other factors, such as the inner ear, seem to constrain mammalian hearing.     

Spatial structure of plant cell wall polysaccharides and its functional significance

Plant polysaccharides comprise the major portion of organic matter in the biosphere. The cell wall built on the basis of polysaccharides is the key feature of a plant organism largely determining its biology. All together, around 10 types of polysaccharide backbones, which can be decorated by different substituents giving rise to endless diversity of carbohydrate structures, are present in cell walls of higher plants. Each of the numerous cell types present in plants has cell wall with specific parameters, the features of which mostly arise from the structure of polymeric components. The structure of polysaccharides is not directly encoded by the genome and has variability in many parameters (molecular weight, length, and location of side chains, presence of modifying groups, etc.). The extent of such variability is limited by the “functional fitting” of the polymer, which is largely based on spatial organization of the polysaccharide and its ability to form supramolecular complexes of an appropriate type. Consequently, the carrier of the functional specificity is not the certain molecular structure but the certain type of the molecules having a certain degree of heterogeneity. This review summarizes the data on structural features of plant cell wall polysaccharides, considers formation of supramolecular complexes, gives examples of tissue- and stage-specific polysaccharides and functionally significant carbohydrate-carbohydrate interactions in plant cell wall, and presents approaches to analyze the spatial structure of polysaccharides and their complexes.     

Serotonin localization and its functional significance during mouse preimplantation embryo development

Serotonin is a neurotransmitter functioning also as a hormone and growth factor. To further investigate the biological role of serotonin during embryo development, we analysed serotonin localization as well as the expression of specific serotonin 5-HT1D receptor mRNA in mouse oocytes and preimplantation embryos. The functional significance of serotonin during the preimplantation period was examined by studying the effects of serotonin on mouse embryo development. Embryo exposure to serotonin (1 microM) highly significantly reduced the mean cell number, whereas lower concentrations of serotonin (0.1 microM and 0.01 microM) had no significant effects on embryo cell numbers. In all serotonin-treated groups a significant increase in the number of embryos with apoptotic and secondary necrotic nuclei was observed. Expression of serotonin 5-HT1D receptor mRNA in mouse oocytes and preimplantation embryos was confirmed by in situ hybridization showing a clearly distinct punctate signal. Immunocytochemistry results revealed the localization of serotonin in oocytes and embryos to the blastocyst stage as diffuse punctate cytoplasmic labelling. It appears that endogenous and/or exogenous serotonin in preimplantation embryos could be involved in complex autocrine/paracrine regulations of embryo development and embryo-maternal interactions.     

Mechanisms of induction of adenosine receptor genes and its functional significance

Adenosine is a metabolite generated and released from cells, particularly under injury or stress. It elicits protective or damaging responses via signaling through the adenosine receptors, including the adenylyl cyclase inhibitory A(1) and A(3), and the adenylyl cyclase stimulatory A(2A) and A(2B). Multiple adenosine receptor types, including stimulatory and inhibitory, can be found in the same cell, suggesting that a careful balance of adenosine receptor expression in a particular cell is necessary for a specific adenosine-induced response. This balance could be controlled by differential expression of the adenosine receptor genes under different stimuli. Here, we have reviewed an array of studies that have characterized basal or induced expression of the adenosine receptors and common as well as distinct mechanisms of effect, in hopes that ongoing studies on this topic will further elucidate detailed mechanisms of adenosine receptor regulation, leading to potential therapeutic applications.     

Light-induced morphological plasticity in the scleractinian coral Goniastrea pectinata and its functional significance

Environment-induced i.e., phenotypically plastic, changes in morphology, are potentially an important life-history component of sessile corals. Previous reciprocal transplant experiments have demonstrated depth-related responses in various coral species, but the potential adaptive significance is rarely investigated. To test for small-scale morphological plasticity in the massive coral Goniastrea pectinata Ehrenberg 1834, fragments from five colonies were reciprocally transplanted between two depths at Raffles Lighthouse (Pulau Satumu), Singapore. After 163 days, all fragments were collected, cleared of tissue, and examined. Reaction norms and multivariate analysis of variance describe light-induced changes in corallite architecture and genotype × environment interactions. In fragments transplanted to the shallow station, calices were deeper, and septa were shorter than in fragments transplanted to the deep station. To explore the functional significance of this plasticity, a two-dimensional model of corallite shape was constructed. The induced calice morphology of the shallow-water transplants was efficient at shading, possibly to protect tissue from excess radiation, whereas the calice morphology found in the deep-water transplants was more efficient at capturing light when irradiance was low.     

Variation in foot size and shape in some British land snails and its functional significance

Live weight, and the length, breadth and surface area of the extended foot sole were measured in 24 species of British terrestrial snails. Allometric relationships between these variables are described, concentrating on the relationship between foot surface area and weight. Intraspecific foot area/weight relationships deviate from isometric expectation for several species; this may be attributed to density changes, foot-shape variation or the physical constraint imposed by shell aperture size.
The rate of increase of foot sole area with live weight among species is greater than expected under isometry, indicating that larger species partially compensate for the increase in foot loading (weight per unit foot area). The rate of whorl expansion of the shell is related to the deviations from the interspecific foot area/weight relationship, reinforcing the possibility that shell aperture area may limit foot size in some species. Foot ratio (foot length:foot width) is negatively related to live weight and foot loading.
The findings are discussed in relation to the known behaviour and microdistribution patterns of the species.     

FMRFamide-like material in the earwig, Euborellia annulipes, and its functional significance.

The neurosecretory system of the earwig, Euborellia annulipes, contained material similar to that of FMRFamide, as shown by immunocytochemistry. Within the brain were two pairs of darkly staining perikarya in the medial protocerebrum, and up to four pairs of immunoreactive cells in the lateral protocerebrum. The corpora allata appeared immunoreactive in 10-day females, but not in 2-day-old adults. Additionally, immunoreactive material was detected in midgut endocrine cells of both 2- and 10-day-old females. FMRFamide at 1 to 100 nM did not inhibit juvenile hormone production by earwig corpora allata in vitro. This was true of glands of low activity from 2-day cat food-fed or starved virgin females, 10-day starved females, and those of relatively high activity from 10-day-old, cat food-fed females. In contrast, FMRFamide at 50 and 100 (but not at 1) nM stimulated gut motility in vitro in distended guts from 2-day fed females. Preparations from starved females and those from 10-day fed females (in which feeding behavior is on the decline) did not respond to exogenous FMRFamide with enhanced rates of contraction. Lastly, preparations from females starved for 7 days and subsequently fed for 3 days responded to 10 nM FMRFamide with increases in gut motility.     

Mechanical coupling of upper and lower canine rib cages and its functional significance

We studied rib cage distortability and reexamined the mechanical action of the diaphragm and the rib cage muscles in six supine anesthetized dogs by measuring changes in upper rib cage cross-sectional area (Aurc) and changes in lower rib cage cross-sectional area (Alrc) and the respective pressures acting on them. During quiet breathing in the intact animal the rib cage behaved as a unit (Aurc: 14.6 +/- 7.9 vs. Alrc: 15.1 +/- 9.6%), whereas considerable distortions of the rib cage occurred during breathing after bilateral phrenicotomy (Aurc: 21.0 +/- 5.1 vs. Alrc: 7.0 +/- 4.8%). These distortions were even more pronounced during phrenic nerve stimulation and separate stimulation of the costal and crural parts of the diaphragm (e.g., phrenic nerve stimulation; Aurc: -7.1 +/- 5.1 vs. Alrc: 6.9 +/- 3.5%). During the latter maneuvers the upper rib cage deflated along the relationship between upper rib cage dimensions and pleural pressure obtained during passive deflation, whereas the lower rib cage inflated close to the relationship between lower rib cage dimensions and abdominal pressure obtained during passive inflation. The latter relationship is expected to differ between costal and crural stimulation, since costal action has both an appositional and insertional component and crural action only has an appositional component. The difference between costal and crural stimulation, however, was relatively small, and the slopes were only slightly steeper for the costal than for the crural stimulation (2.9 +/- 1.2 vs. 2.2 +/- 1.0%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hermaphroditism in molluscs

The functional significance of hermaphroditism is, as yet, not well understood. This study attempts to examine the relevance of some theories on this topic to reality, by reviewing the literature on hermaphroditism among molluscs. The study reveals that about 40% of the 5600 mollusc genera are either simultaneous or sequential hermaphrodites. Hermaphroditism occurs in 100% of the Solenogastres, 99% of the Opisthobranchia, 100% of the Pulmonata, 3% of the Prosobranchia and 9% of the Bivalvia. Sequential hermaphroditism, whatever its theoretical advantages over gonochorism, is not common among molluscs. Simultaneous hermaphroditism is common among the Euthyneura. Over 80% of the hermaphroditic genera belong to the Euthyneura (about 2000 recent genera), and over 99% of the Euthyneura are hermaphrodites. The almost ubiquitous occurrence of hermaphroditism throughout the Euthyneurans, coupled with this group's very widespread dispersal in marine, terrestrial and freshwater habitats (and corresponding exposure to a very wide range of predators, competitors or parasites); and also its wide range of population densities, suggests that in this group hermaphroditism is not an adaptive response to selective forces of the environment and it may well be a phylogenetic constraint. A few stylommatophorans have broken this constraint by possessing genitalia in which the male system is absent (aphally) or extremely reduced (hemiphally). They reproduce by self-fertilization. In theory this is advantageous in that these species save the cost of developing two sets of reproductive apparatus. In reality there is no record of aphally occurring throughout an entire species, as one may expect if this saving of cost were so overwhelmingly advantageous. There is also no record of stylommatophoran individuals developing only the male system, as one may expect if there was any evolutionary trend from hermaphroditism towards gonochorism. Simultaneous hermaphroditism offers a (theoretical) option to selling. Selfing by self-fertilization is widespread among freshwater basommatophorans, amphibious stylommatophorans and freshwater bivalves. Selfing by parthenogenesis is widespread among freshwater prosobranchs. Altogether, of 48 genera which self, 60% are dwellers of freshwater. Certain freshwater habitats may perhaps be less stable than most marine or terrestrial ones are. Beyond the Euthyneura, hermaphroditism is common among parasitic, deep sea and Cnidaria-eating molluscs. Perhaps these three associations should be slightly rearranged and combined into a single generalization: that hermaphroditism (beyond the Euthyneura) is widespread among molluscs that live in a close and permanent intimacy with live marine invertebrates, whether as parasites, commensals or predators. Gonochorism but with dwarf males is common among the Eulimoidea, which are parasites, and Galeommatoidea, which are commensals. This situation of gonochorism, in which there is a very close association between members of the two sexes, is functionally a hermaphroditic type. Animals that can manipulate the physiology and endocrinology of their hosts may also have the tendency and ability to manipulate the size of their own males. It may well be that the female not only determines the size of the male but also his sex, in which case dwarf males should be considered as a case of environmental sex determination. The theoretical possibility that hermaphroditism may evolve in brooding animals was examined in gastropods. Among the (predominantly gonochoric) prosobranchs brooding is recorded in 85 genera (4%), only two of which are hermaphrodites. Among the (predominantly hermaphrodite) heterobranchs it is recorded in only 95 odd genera (4%). When all gastropod genera are considered together, the frequency of hermaphroditism among the brooders is only very slightly and insignificantly higher than in the non-brooders. When only the prosobranchs are considered, the frequency of hermaphroditism among the brooders is actually lower than among non-brooders. The theory that hermaphroditism evolves in brooding animals thus appears not to be relevant to the vast majority of gastropods. Brooding is widespread among freshwater prosobranchs (48% of the brooding genera). In this habitat, brooding may perhaps be an adaptation to protect the developing embryo against osmotic stresses.     

Polymerization of human angiotensinogen: insights into its structural mechanism and functional significance

In the present study, we have investigated the in vitro polymerization of human plasma AGT (angiotensinogen), a non-inhibitory member of the serpin (SERine Protease INhibitor) family. Polymerization of AGT is thought to contribute to a high molecular mass form of the protein in plasma that is increased in pregnancy and pregnancy-associated hypertension. The results of the present study demonstrate that the polymerization of AGT occurs through a novel mechanism which is primarily dependent on non-covalent linkages, while additional disulfide linkages formed after prolonged incubation are not essential for either formation or stability of polymers. We present the first analyses of AGT polymers by electron microscopy, CD spectroscopy, stability assays and sensitivity to proteinases and we conclude that their structure differs from the 'loop-sheet' polymers typical of inhibitory serpins. Histidine residues within the unique N-terminal extension of AGT appear to influence polymer formation, although polymer formation can still take place after their removal by renin. At a functional level, we show that AGT polymers are not substrates for renin, so polymerization of AGT in plasma would predictably lead to decreased formation of AngI (angiotensin I) with blood pressure lowering. Polymerization may therefore be an appropriate response to hypertension. The ability of AGT to protect its renin cleavage site through polymerization may explain why the AngI decapeptide has remained linked to the large and apparently inactive serpin body throughout evolution.