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Complex Mechanisms (complex + mechanism)
Selected AbstractsComplex mechanisms of sensory tricks in cervical dystoniaMOVEMENT DISORDERS, Issue 4 2004Axel Schramm MD Abstract Muscle activities in 26 patients with predominantly rotational torticollis were quantified using surface electromyography. In the subgroup of 19 patients with an effective sensory trick, different modes and bilateral locations of trick application led to significant (P < 0.002) reduction of electromyographic (EMG) activity. A strong correlation was found between the efficacy of trick manoeuvres and the starting head position. Trick application in a neutral or even contralateral position was most effective while no reduction of muscle activity during trick application at the maximum dystonic head position was found (P < 0.001). We propose a two-phase model: First, normalisation of head posture is obtained by counterpressure or volitional antagonistic muscle activity. In a second step, this position can be stabilised using sensory tricks challenging central adaption of distorted sensorimotor integration. © 2003 Movement Disorder Society [source] Expression and functional analysis of Tgif during mouse midline developmentDEVELOPMENTAL DYNAMICS, Issue 2 2006Jiu-Zhen Jin Abstract The Tgif gene encodes a homeodomain protein that functions as a transforming growth factor beta (TGF-,) repressor by binding to Smad2. Mutations in the TGIF gene are associated with human holoprosencephaly, a common birth defect caused by the failure of anterior ventral midline formation. However, Smad2-mediated TGF-, signaling in the axial mesendoderm has been demonstrated to be essential for ventral midline formation, and loss of a Smad2 antagonist should in principle promote rather than inhibit ventral midline formation. This suggests a more complex mechanism for the function of TGIF in controlling ventral midline formation. To explore the role of TGIF in ventral forebrain formation and patterning, we investigated Tgif expression and function during mouse development by in situ hybridization and gene targeting. We found that Tgif is highly expressed in the anterior neural plate, consistent with the proposed neural differentiation model in which TGF-, suppression is required for normal neural differentiation. This result suggests a possible role for Tgif in anterior neural differentiation and patterning. However, targeted disruption of the Tgif gene during mouse development does not cause any detectable defects in development and growth. Both histological examination and gene expression analysis showed that Tgif,/, embryos have a normal ventral specification in the central nervous system, including the forebrain region. One interpretation of these results is that the loss of TGIF function is compensated by other TGF-, antagonists such as c-Ski and SnoN during vertebrate anterior neural development. Developmental Dynamics 235:547,553, 2006. © 2005 Wiley-Liss, Inc. [source] Economic evaluation of demand-side energy storage systems by using a multi-agent-based electricity marketELECTRICAL ENGINEERING IN JAPAN, Issue 3 2009Ken Furusawa Abstract With the wholesale electric power market opened in April 2005, deregulation of the electric power industry in Japan has faced a new competitive environment. In the new environment, Independent Power Producer (IPP), Power Producer and Supplier (PPS), Load Service Entity (LSE), and electric utility can trade electric energy through both bilateral contracts and single-price auction at the electricity market. In general, the market clearing price (MCP) is largely changed by the amount of total load demand in the market. The influence may cause a price spike, and consequently the volatility of MCP will make LSEs and their customers face a risk of higher revenue and cost. DSM is attractive as a means of load leveling, and has an effect on decreasing MCP at peak load period. Introducing Energy Storage systems (ES) is one DSM in order to change demand profile at the customer side. In the case that customers decrease their own demand due to increased MCP, a bidding strategy of generating companies may be changed. As a result, MCP is changed through such complex mechanism. In this paper the authors evaluate MCP by multi-agent. It is considered that customer-side ES has an effect on MCP fluctuation. Through numerical examples, this paper evaluates the influence on MCP by controlling customer-side ES corresponding to variation of MCP. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 167(3): 36,45, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20658 [source] Splitting of the fission yeast septumFEMS YEAST RESEARCH, Issue 6 2007Matthias Sipiczki Abstract In cell-walled organisms, a cross wall (septum) is produced during cytokinesis, which then splits in certain organisms to allow the daughter cells to separate. The formation and the subsequent cleavage of the septum require wall synthesis and wall degradation, which need to be strictly coordinated in order to prevent cell lysis. The dividing fission yeast (Schizosaccharomyces) cell produces a three-layered septum in which the middle layer and a narrow band of the adjacent cell wall can be degraded without threatening the integrity of the separating daughter cells. This spatially very precise process requires the activity of the Agn1p 1,3-,-glucanase and the Eng1p 1,3-,-glucanase, which are localized to the septum by a complex mechanism involving the formation of a septin ring and the directed activity of the exocyst system. The Sep1p-Ace2p transcription-factor cascade regulates the expression of many genes producing proteins for this complex process. Recent advances in research into the molecular mechanisms of separation and its regulation are discussed in this review. [source] Evidence for Antinociceptive Activity of Botulinum Toxin Type A in Pain ManagementHEADACHE, Issue 2003K. Roger Aoki PhD The neurotoxin, botulinum toxin type A, has been used successfully, in some patients, as an analgesic for myofascial pain syndromes, migraine, and other headache types. The toxin inhibits the release of the neurotransmitter, acetylcholine, at the neuromuscular junction thereby inhibiting striated muscle contractions. In the majority of pain syndromes where botulinum toxin type A is effective, inhibiting muscle spasms is an important component of its activity. Even so, the reduction of pain often occurs before the decrease in muscle contractions suggesting that botulinum toxin type A has a more complex mechanism of action than initially hypothesized. Current data points to an antinociceptive effect of botulinum toxin type A that is separate from its neuromuscular activity. The common biochemical mechanism, however, remains the same between botulinum toxin type A's effect on the motor nerve or the sensory nerve: enzymatic blockade of neurotransmitter release. The antinociceptive effect of the toxin was reported to block substance P release using in vitro culture systems.1 The current investigation evaluated the in vivo mechanism of action for the antinociceptive action of botulinum toxin type A. In these studies, botulinum toxin type A was found to block the release of glutamate. Furthermore, Fos, a product of the immediate early gene, c- fos, expressed with neuronal stimuli was prevented upon peripheral exposure to the toxin. These findings suggest that botulinum toxin type A blocks peripheral sensitization and, indirectly, reduces central sensitization. The recent hypothesis that migraine involves both peripheral and central sensitization may help explain how botulinum toxin type A inhibits migraine pain by acting on these two pathways. Further research is needed to determine whether the antinociceptive mechanism mediated by botulinum toxin type A affects the neuronal signaling pathways that are activated during migraine. [source] Synaptic Transmission: Inhibition of Neurotransmitter Release by Botulinum ToxinsHEADACHE, Issue 2003Oliver Dolly MSc Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation. At the neuromuscular junction, the presynaptic nerve ending is packed with synaptic vesicles filled with acetylcholine, and clustered at the tip of the folds of the postsynaptic muscle membrane are the acetylcholine receptors. Synaptic vesicles fuse with the membrane in response to an elevation of intraneuronal calcium concentration and undergo release of their transmitter by exocytosis. Intracellular proteins that contribute to the fusion of the vesicles with the plasma membrane during exocytosis include synaptosomal protein with a molecular weight of 25 kDa (SNAP-25); vesicle-associated membrane protein (VAMP), also known as synaptobrevin; and syntaxin. Through their proteolytic action on these proteins, botulinum toxins prevent exocytosis, thereby inhibiting the release of acetylcholine. There are 7 serotypes of this toxin,A, B, C1, D, E, F, and G,and each cleaves a different intracellular protein or the same target at distinct bonds. The separate cleavage sites in SNAP-25 for botulinum toxin types A and E contribute to their dissimilar durations of muscle relaxation. This report describes the molecular basis for the inhibition by botulinum toxins of neuroexocytosis and subsequent functional recovery at the neuromuscular junction. [source] Investigating the impact of the Chi-Chi earthquake on the occurrence of debris flows using artificial neural networksHYDROLOGICAL PROCESSES, Issue 19 2009Fi-John Chang Abstract Debris flows have caused enormous losses of property and human life in Taiwan during the last two decades. An efficient and reliable method for predicting the occurrence of debris flows is required. The major goal of this study is to explore the impact of the Chi-Chi earthquake on the occurrence of debris flows by applying the artificial neural network (ANN) that takes both hydrological and geomorphologic influences into account. The Chen-Yu-Lan River watershed, which is located in central Taiwan, is chosen for evaluating the critical rainfall triggering debris flows. A total of 1151 data sets were collected for calibrating model parameters with two training strategies. Significant differences before and after the earthquake have been found: (1) The size of landslide area is proportioned to the occurrence of debris flows; (2) the amount of critical rainfall required for triggering debris flows has reduced significantly, about half of the original critical rainfall in the study case; and (3) the frequency of the occurrence of debris flows is largely increased. The overall accuracy of model prediction in testing phase has reached 96·5%; moreover, the accuracy of occurrence prediction is largely increased from 24 to 80% as the network trained with data from before the Chi-Chi earthquake sets and with data from the lumped before and after the earthquake sets. The results demonstrated that the ANN is capable of learning the complex mechanism of debris flows and producing satisfactory predictions. Copyright © 2009 John Wiley & Sons, Ltd. [source] OH hydrogen abstraction reactions from alanine and glycine: A quantum mechanical approachJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 11 2001Annia Galano Abstract Density functional theory (B3LYP and BHandHLYP) and unrestricted second-order Møller,Plesset (MP2) calculations have been performed using 3-21G, 6-31G(d,p), and 6-311 G(2d,2p) basis sets, to study the OH hydrogen abstraction reaction from alanine and glycine. The structures of the different stationary points are discussed. Ring-like structures are found for all the transition states. Reaction profiles are modeled including the formation of prereactive complexes, and very low or negative net energy barriers are obtained depending on the method and on the reacting site. ZPE and thermal corrections to the energy for all the species, and BSSE corrections for B3LYP activation energies are included. A complex mechanism involving the formation of a prereactive complex is proposed, and the rate coefficients for the overall reactions are calculated using classical transition state theory. The predicted values of the rate coefficients are 3.54×108 L,mol,1,s,1 for glycine and 1.38×109 L,mol,1,s,1 for alanine. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1138,1153, 2001 [source] Glucose-regulated protein 78: A new partner of p53 in trophoblastPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 23 2009Serge Arnaudeau Abstract Although wild-type p53 protein is overexpressed in first trimester trophoblast, it is inactive towards its target genes Metalloproteinase 2 and 9. This seems to be due to a complex mechanism of inactivation and stabilization of p53 relying on the formation of protein complexes involving the N-terminus of p53. To detect the proteins associated with this sequence, we incubated biotinylated p53 N-terminal peptide in cytotrophoblastic cell medium 24,h before lysis of cells. We purified the proteins retained on biotinylated peptide using a neutravidin affinity column. Proteins were then identified by peptide mass finger printing followed or not by peptide fragmentation sequencing. Among these proteins, we identified glucose-regulated protein 78 (GRP78) and verified its interaction with p53 in trophoblastic cells by immunoprecipitation and Western blot analysis. Moreover, the decreased expression of GRP78 induced by GRP78siRNA or versipelostatin decreased the formation of high molecular weight p53 complexes and p53 monomer and increased trophoblastic invasion. These results suggest that GRP78 is involved in inactivation and stabilization of p53 and in the regulation of trophoblastic invasion. [source] DISRUPTING ILLEGAL FIREARMS MARKETS IN BOSTON: THE EFFECTS OF OPERATION CEASEFIRE ON THE SUPPLY OF NEW HANDGUNS TO CRIMINALS,CRIMINOLOGY AND PUBLIC POLICY, Issue 4 2005ANTHONY A. BRAGA Research Summary: The question of whether the illegal firearms market serving criminals and juveniles can be disrupted has been vigorously debated in policy circles and in the literature on firearms and violence. To the extent that prohibited persons, in particular, are supplied with guns through systematic gun trafficking, focused regulatory and investigative resources may be useful in disrupting the illegal supply of firearms to criminals. In Boston, a gun market disruption strategy was implemented that focused on shutting down illegal diversions of new handguns from retail sources. Multivariate regression analyses were used to estimate the effects of the intervention on new handguns recovered in crime. Our results suggest that focused enforcement efforts, guided by strategic analyses of ATF firearms trace data, can have significant impacts on the illegal supply of new handguns to criminals. Policy Implications: The problem-oriented policing approach provides an appropriate framework to uncover the complex mechanisms at play in illicit firearms markets and to develop tailor-made interventions to disrupt the illegal gun trade. Strategic enforcement programs focused on the illegal diversion of new firearms from primary markets can reduce the availability of new guns to criminals. However, the extent to which criminals substitute older guns for new guns and move from primary markets to secondary markets in response to an enforcement strategy focused on retail outlets remains unclear. Our evaluation also does not provide policy makers with any firm evidence on whether supply-side enforcement strategies have any measurable impacts on gun violence. Jurisdictions suffering from gun violence problems should implement demand-side violence prevention programs to complement their supply-side efforts. [source] Crystal growth and structural refinement of NaMn7O12CRYSTAL RESEARCH AND TECHNOLOGY, Issue 10-11 2005E. Gilioli Abstract We report the crystal growth and the structural refinement of NaMn7O12, a manganite having a double perovskite structure. As in many similar compounds, there is coexistence of Mn3+ and Mn4+ but in this material they orderly occupy different sites for crystallographic reasons. Therefore, this peculiar structure can be considered as a model system for studying complex mechanisms such as charge, orbital and spin ordering. High purity bulk samples and "large" single crystals are needed to study tiny modifications in the crystallographic and magnetic structures associated to the ordering phenomena. Almost single phase (more than 96% pure) and single crystals (up to about 150 µm) of NaMn7O12 were synthesized by solid state reaction under pressure in a multi-anvil apparatus. Single crystal x-ray diffraction and SEM analysis have been used to characterize the crystals. The structure refinement indicates that NaMn7O12 crystallizes in the cubic Im3 space group, with a = 7.312 Å and Z = 2. Further studies are in progress to optimize the synthesis conditions, in order to grow larger crystals. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] The metacommunity concept: a framework for multi-scale community ecologyECOLOGY LETTERS, Issue 7 2004M. A. Leibold Abstract The metacommunity concept is an important way to think about linkages between different spatial scales in ecology. Here we review current understanding about this concept. We first investigate issues related to its definition as a set of local communities that are linked by dispersal of multiple potentially interacting species. We then identify four paradigms for metacommunities: the patch-dynamic view, the species-sorting view, the mass effects view and the neutral view, that each emphasizes different processes of potential importance in metacommunities. These have somewhat distinct intellectual histories and we discuss elements related to their potential future synthesis. We then use this framework to discuss why the concept is useful in modifying existing ecological thinking and illustrate this with a number of both theoretical and empirical examples. As ecologists strive to understand increasingly complex mechanisms and strive to work across multiple scales of spatio-temporal organization, concepts like the metacommunity can provide important insights that frequently contrast with those that would be obtained with more conventional approaches based on local communities alone. [source] Polygenic Control of Idiopathic Generalized Epilepsy Phenotypes in the Genetic Absence Rats from Strasbourg (GAERS)EPILEPSIA, Issue 4 2004Gabrielle Rudolf Summary: Purpose: Generalized nonconvulsive absence seizures are characterized by the occurrence of synchronous and bilateral spike-and-wave discharges (SWDs) on electroencephalographic recordings, concomitant with behavioral arrest. The GAERS (genetic absence rats from Strasbourg) strain, a well-characterized inbred model for idiopathic generalized epilepsy, spontaneously develops EEG paroxysms that resemble those of typical absence seizures. The purpose of this study was to investigate the genetic control of SWD variables by using a combination of genetic analyses and electrophysiological measurements in an experimental cross derived from GAERS and Brown Norway (BN) rats. Methods: SWD subphenotypes were quantified on EEG recordings performed at both 3 and 6 months in a cohort of 118 GAERS × BN F2 animals. A genome-wide scan of the F2 progenies was carried out with 146 microsatellite markers that were used to test each marker locus for evidence of genetic linkage to the SWD quantitative traits. Results: We identified three quantitative trait loci (QTLs) in chromosomes 4, 7, and 8 controlling specific SWD variables in the cross, including frequency, amplitude, and severity of SWDs. Age was a major factor influencing the detection of genetic linkage to the various components of the SWDs. Conclusions: The identification of these QTLs demonstrates the polygenic control of SWDs in the GAERS strain. Genetic linkages to specific SWD features underline the complex mechanisms contributing to SWD development in idiopathic generalized epilepsy. [source] Biallelic deletion 13q14.3 in patients with chronic lymphocytic leukemia: cytogenetic, FISH and clinical studiesEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2008Christian Chena Abstract Background and objective:, Monoallelic deletion of 13q14.3 (13q14x1) is the most common abnormality in chronic lymphocytic leukemia (CLL). As a sole alteration, it predicts a favorable outcome. Biallelic 13q14.3 (13q14x2) deletion or concomitant 13q14x1/13q14x2 has been scarcely evaluated in the literature. We present the clinical, cytogenetic and fluorescence in situ hybridization (FISH) analysis of six CLL patients with normal karyotypes and 13q14x2 and their comparison to cases with 13q14x1 as a single abnormality. Patients and methods:, A total of 103 CLL patients were studied. Cytogenetic and FISH analysis were performed on stimulated peripheral blood lymphocytes. Specific fluorescence DNA probes for CLL were used. Results:, Six out of 103 (5.8%) patients showed normal karyotypes and 13q14x2. It was observed as a single alteration in one patient and combined with 13q14x1 in five cases. Biallelic clones were larger than monoallelic ones in 3/5 patients (60%). The comparison of clinical and hematological data between 13q14x1 and 13q14x2 groups showed progression of the disease in all 13q14x2 patients respect to 12/32 (37.5%) cases with 13q14x1 (P = 0.008), significant differences in the distribution by Rai stage (P = 0.042) and a tendency of a higher lactate dehydrogenase level in 13q14x2 patients (P = 0.054). Treatment free survival for 13q14x2 group was 28.5 months, shorter than those observed in patients with 13q14x1 alone (49 months). Conclusions:, Our data would suggest that 13q14x2 could represent a more aggressive FISH anomaly than 13q14x1 alone, probably as a consequence of clonal evolution and/or due to the complete inactivation of this critical region by mean of more complex mechanisms. [source] Pathophysiology of pruritus in atopic dermatitis: an overviewEXPERIMENTAL DERMATOLOGY, Issue 1 2002Sonja Ständer Abstract: Pruritus is an essential feature of atopic dermatitis (AD) and the diagnosis of active AD cannot be made without the history of itching. Because of the high impact on life quality, most of the patients measure the severity of eczema by the intensity of pruritus rather than appearance of skin lesions. However, although pruritus is a cardinal symptom of AD, its mechanism and association with the cutaneous nervous system is not completely understood. Recently, a considerable progress has been achieved in clarifying the complex pathophysiology of pruritus in AD. As a cutaneous sensory perception, itch requires excitation of neuropeptide-containing free nerve endings of unmyelinated nociceptor fibers. It is well known that histamine and acetylcholine provoke itch by direct binding to ,itch receptors' and several mediators such as neuropeptides, proteases or cytokines indirectly via histamine release. Interestingly, some variations of these complex mechanisms could be demonstrated in patients with AD. This review highlights the recent knowledge of different mechanisms which may be involved in regulating pruritus in patients with AD potentially leading to new therapeutic applications for the treatment of itch in AD. [source] Penicillin Binding Proteins: key players in bacterial cell cycle and drug resistance processesFEMS MICROBIOLOGY REVIEWS, Issue 5 2006Pauline Macheboeuf Abstract Bacterial cell division and daughter cell formation are complex mechanisms whose details are orchestrated by at least a dozen different proteins. Penicillin-binding proteins (PBPs), membrane-associated macromolecules which play key roles in the cell wall synthesis process, have been exploited for over 70 years as the targets of the highly successful ,-lactam antibiotics. The increasing incidence of ,-lactam resistant microorganisms, coupled to progress made in genomics, genetics and immunofluorescence microscopy techniques, have encouraged the intensive study of PBPs from a variety of bacterial species. In addition, the recent publication of high-resolution structures of PBPs from pathogenic organisms have shed light on the complex intertwining of drug resistance and cell division processes. In this review, we discuss structural, functional and biological features of such enzymes which, albeit having initially been identified several decades ago, are now being aggressively pursued as highly attractive targets for the development of novel antibiotherapies. [source] Unraveling Deterministic Mesoscopic Polarization Switching Mechanisms: Spatially Resolved Studies of a Tilt Grain Boundary in Bismuth FerriteADVANCED FUNCTIONAL MATERIALS, Issue 13 2009Brian J. Rodriguez Abstract The deterministic mesoscopic mechanism of ferroelectric domain nucleation is probed at a single atomically-defined model defect: an artificially fabricated bicrystal grain boundary (GB) in an epitaxial bismuth ferrite film. Switching spectroscopy piezoresponse force microscopy (SS-PFM) is used to map the variation of local hysteresis loops at the GB and in its immediate vicinity. It is found that the the influence of the GB on nucleation results in a slight shift of the negative nucleation bias to larger voltages. The mesoscopic mechanisms of domain nucleation in the bulk and at the GB are studied in detail using phase-field modeling, elucidating the complex mechanisms governed by the interplay between ferroelectric and ferroelastic wall energies, depolarization fields, and interface charge. The combination of phase-field modeling and SS-PFM allows quantitative analysis of the mesoscopic mechanisms for polarization switching, and hence suggests a route for unraveling the mechanisms of polarization switching at a single defect level and ultimately optimizing materials properties through microstructure engineering. [source] Epigenetics and T helper 1 differentiationIMMUNOLOGY, Issue 3 2009Thomas M. Aune Summary Naïve T helper cells differentiate into two subsets, T helper 1 and 2, which either transcribe the Ifng gene and silence the Il4 gene or transcribe the Il4 gene and silence the Ifng gene, respectively. This process is an essential feature of the adaptive immune response to a pathogen and the development of long-lasting immunity. The ,histone code' hypothesis proposes that formation of stable epigenetic histone marks at a gene locus that activate or repress transcription is essential for cell fate determinations, such as T helper 1/T helper 2 cell fate decisions. Activation and silencing of the Ifng gene are achieved through the creation of stable epigenetic histone marks spanning a region of genomic DNA over 20 times greater than the gene itself. Key transcription factors that drive the T helper 1 lineage decision, signal transducer and activator 4 (STAT4) and T-box expressed in T cells (T-bet), play direct roles in the formation of activating histone marks at the Ifng locus. Conversely, STAT6 and GATA binding protein 3, transcription factors essential for the T helper 2 cell lineage decision, establish repressive histone marks at the Ifng locus. Functional studies demonstrate that multiple genomic elements up to 50 kilobases from Ifng play critical roles in its proper transcriptional regulation. Studies of three-dimensional chromatin conformation indicate that these distal regulatory elements may loop towards Ifng to regulate its transcription. We speculate that these complex mechanisms have evolved to tightly control levels of interferon-, production, given that too little or too much production would be very deleterious to the host. [source] Aspects of the reproductive biology and breeding management of Asian and African elephants Elephas maximus and Loxodonta africanaINTERNATIONAL ZOO YEARBOOK, Issue 1 2006T. B. HILDEBRANDT Elephants possess many unique qualities, including some that relate directly to their reproductive biology. Thus, comparative studies on elephants provide valuable information to the growing biological database for extant mammals. Left undisturbed, Asian Elephas maximus and African Loxodonta Africana elephants reproduce well in the wild. It is ironic then that most captive populations face possible,extinction'because of historically poor reproductive performance. Some of the problems with breeding elephants in captivity are logistical but others, like ovarian and uterine pathologies and bull infertility, have management-related aetiology. Through advances in endocrine monitoring and ultrasound imaging techniques, we are beginning to understand some of the complex mechanisms controlling reproductive function in elephants. Several reproductive characteristics appear to be unique to the taxon, such as luteal steroidogenic function, follicular development patterns, pituitary gonadotrophin secretion, a 22 month-long gestation and musth (in ,,). One example is the,double LH surge'occurring 3 weeks apart during the follicular or non-luteal phase of the cycle, with only the second surge inducing ovulation. These qualities have at times both enhanced and hampered efforts to understand and control reproduction. We have learned that techniques developed for domestic or laboratory species are not always directly applicable to elephants. However, the recent success of artificial insemination based on new ultrasound and endocrine methodology offers hope that establishing selfsustaining populations is possible. This paper reviews our current knowledge of elephant reproduction and how it is being used to aid species conservation for maximal reproductive efficiency and enhancement of genetic management. [source] The Ganglioside GD3 as the Greek Goddess Hecate: Several Faces Turned Towards as Many DirectionsIUBMB LIFE, Issue 7 2005Florence Malisan Abstract The disialoganglioside GD3 can mediate biological functions as diverse as proliferation, differentiation, and apoptosis. Since intracellular level of GD3 is crucial for the cell, understanding the mechanisms by which GD3 metabolism is tightly regulated seems of particular importance. GD3 can be enlisted among the most potent natural inducers of mitochondrial damage and apoptosis. However, some cell types resist GD3-mediated mitochondrial damage through complex mechanisms which are beginning to be unveiled. IUBMB Life, 57: 477-482, 2005 [source] Role of hypoxia in the hallmarks of human cancerJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2009Kai Ruan Abstract Hypoxia has been recognized as one of the fundamentally important features of solid tumors and plays a critical role in various cellular and physiologic events, including cell proliferation, survival, angiogenesis, immunosurveillance, metabolism, as well as tumor invasion and metastasis. These responses to hypoxia are at least partially orchestrated by activation of the hypoxia-inducible factors (HIFs). HIF-1 is a key regulator of the response of mammalian cells to oxygen deprivation and plays critical roles in the adaptation of tumor cells to a hypoxic microenvironment. Hypoxia and overexpression of HIF-1 have been associated with radiation therapy and chemotherapy resistance, an increased risk of invasion and metastasis, and a poor clinical prognosis of solid tumors. The discovery of HIF-1 signaling has led to a rapidly increasing understanding of the complex mechanisms involved in tumor hypoxia and has helped greatly in screening novel anticancer agents. In this review, we will first introduce the cellular responses to hypoxia and HIF-1 signaling pathway in hypoxia, and then summarize the multifaceted role of hypoxia in the hallmarks of human cancers. J. Cell. Biochem. 107: 1053,1062, 2009. © 2009 Wiley-Liss, Inc. [source] Skin hydration: a review on its molecular mechanismsJOURNAL OF COSMETIC DERMATOLOGY, Issue 2 2007Sylvie Verdier-Sévrain MD Summary Water is absolutely essential for the normal functioning of the skin and especially its outer layer, the stratum corneum (SC). Loss of water from the skin must be carefully regulated, a function dependent on the complex nature of the SC. The retention of water in the SC is dependent on two major components: (1) the presence of natural hygroscopic agents within the corneocytes (collectively referred to as natural moisturizing factor) and (2) the SC intercellular lipids orderly arranged to form a barrier to transepidermal water loss (TEWL). The water content of the SC is necessary for proper SC maturation and skin desquamation. Increased TEWL impairs enzymatic functions required for normal desquamation resulting in the visible appearance of dry, flaky skin. There have been recent discoveries regarding the complex mechanisms of skin hydration. In particular, it has been discovered that glycerol, a well-known cosmetic ingredient, exists in the SC as a natural endogenous humectant. Hyaluronan, which has been regarded mainly as dermal component, is found in the epidermis and is important for maintaining normal SC structure and epidermal barrier function. More importantly, the discovery of the existence of the water-transporting protein aquaporin-3 in the viable epidermis and the presence of tight junction structures at the junction between the stratum granulosum and SC have brought new insights into the mechanisms of skin water distribution and barrier function. [source] Plant neurobiology and green plant intelligence: science, metaphors and nonsenseJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 3 2008Paul C Struik Abstract This paper analyses the recent debates on the emerging science of plant neurobiology, which claims that the individual green plant should be considered as an intelligent organism. Plant neurobiology tries to use elements from animal physiology as elegant metaphors to trigger the imagination in solving complex plant physiological elements of signalling, internal and external plant communication and whole-plant organisation. Plant neurobiology proposes useful concepts that stimulate discussions on plant behaviour. To be considered a new science, its added value to existing plant biology needs to be presented and critically evaluated. A general, scientific approach is to follow the so-called ,parsimony principle', which calls for simplest ideas and the least number of assumptions for plausible explanation of scientific phenomena. The extent to which plant neurobiology agrees with or violates this general principle needs to be examined. Nevertheless, innovative ideas on the complex mechanisms of signalling, communication, patterning and organisation in higher plants are badly needed. We present current views on these mechanisms and the specific role of auxins in regulating them. Copyright © 2007 Society of Chemical Industry [source] Relation between inflammation and symptoms in asthmaALLERGY, Issue 3 2009I. Tillie-Leblond Asthma symptoms are the main reason for healthcare utilization and are a fundamental parameter for the evaluation of asthma control. Currently, asthma is defined as a chronic inflammatory disease. A French expert group studied the association between inflammation and asthma symptoms by carrying out a critical review of the international literature. Uncontrolled asthmatics have an increased number of polynuclear eosinophils in the induced sputum and an increased production of exhaled NO. Control by anti-inflammatory treatment is accompanied by a reduction in bronchial eosinophilia and exhaled NO. Asthma symptoms are the result of complex mechanisms and many factors modify their perception. Experimental data suggest that there is a relationship between the perception of symptoms and eosinophilic inflammation and that inhaled corticoid therapy improves this perception. Although they are still not applicable in routine practice, follow-up strategies based on the evaluation of inflammation are thought to be more effective in reducing exacerbations than those usually recommended based on symptoms and sequential analysis of respiratory function. Inhaled corticosteroid therapy is the reference disease-modifying therapy for persistent asthma. Recent studies demonstrated that adjustment of anti-inflammatory treatment based on symptoms is an effective strategy to prevent exacerbations and reduce the total number of doses of inhaled corticosteroids. [source] Cloning and characterization of small RNAs from Medicago truncatula reveals four novel legume-specific microRNA familiesNEW PHYTOLOGIST, Issue 1 2009Guru Jagadeeswaran Summary ,,MicroRNAs (miRNAs) and small-interfering RNAs (siRNAs) have emerged as important regulators of gene expression in higher eukaryotes. Recent studies indicate that genomes in higher plants encode lineage-specific and species-specific miRNAs in addition to the well-conserved miRNAs. Leguminous plants are grown throughout the world for food and forage production. To date the lack of genomic sequence data has prevented systematic examination of small RNAs in leguminous plants. Medicago truncatula, a diploid plant with a near-completely sequenced genome has recently emerged as an important model legume. ,,We sequenced a small RNA library generated from M. truncatula to identify not only conserved miRNAs but also novel small RNAs, if any. ,,Eight novel small RNAs were identified, of which four (miR1507, miR2118, miR2119 and miR2199) are annotated as legume-specific miRNAs because these are conserved in related legumes. Three novel transcripts encoding TIR-NBS-LRR proteins are validated as targets for one of the novel miRNA, miR2118. Small RNA sequence analysis coupled with the small RNA blot analysis, confirmed the expression of around 20 conserved miRNA families in M. truncatula. Fifteen transcripts have been validated as targets for conserved miRNAs. We also characterized Tas3-siRNA biogenesis in M. truncatula and validated three auxin response factor (ARF) transcripts that are targeted by tasiRNAs. ,,These findings indicate that M. truncatula and possibly other related legumes have complex mechanisms of gene regulation involving specific and common small RNAs operating post-transcriptionally. [source] Systemin-dependent salinity tolerance in tomato: evidence of specific convergence of abiotic and biotic stress responsesPHYSIOLOGIA PLANTARUM, Issue 1 2010Francesco Orsini Plants have evolved complex mechanisms to perceive environmental cues and develop appropriate and coordinated responses to abiotic and biotic stresses. Considerable progress has been made towards a better understanding of the molecular mechanisms of plant response to a single stress. However, the existence of cross-tolerance to different stressors has proved to have great relevance in the control and regulation of organismal adaptation. Evidence for the involvement of the signal peptide systemin and jasmonic acid in wound-induced salt stress adaptation in tomato has been provided. To further unravel the functional link between plant responses to salt stress and mechanical damage, transgenic tomato (Lycopersicon esculentum Mill.) plants constitutively expressing the prosystemin cDNA have been exposed to a moderate salt stress. Prosystemin over-expression caused a reduction in stomatal conductance. However, in response to salt stress, prosystemin transgenic plants maintained a higher stomatal conductance compared with the wild-type control. Leaf concentrations of abscissic acid (ABA) and proline were lower in stressed transgenic plants compared with their wild-type control, implying that either the former perceived a less stressful environment or they adapted more efficiently to it. Consistently, under salt stress, transgenic plants produced a higher biomass, indicating that a constitutive activation of wound responses is advantageous in saline environment. Comparative gene expression profiling of stress-induced genes suggested that the partial stomatal closure was not mediated by ABA and/or components of the ABA signal transduction pathway. Possible cross-talks between genes involved in wounding and osmotic stress adaptation pathways in tomato are discussed. [source] Phosphate sensing in higher plantsPHYSIOLOGIA PLANTARUM, Issue 1 2002Steffen Abel Phosphate (Pi) plays a central role as reactant and effector molecule in plant cell metabolism. However, Pi is the least accessible macronutrient in many ecosystems and its low availability often limits plant growth. Plants have evolved an array of molecular and morphological adaptations to cope with Pi limitation, which include dramatic changes in gene expression and root development to facilitate Pi acquisition and recycling. Although physiological responses to Pi starvation have been increasingly studied and understood, the initial molecular events that monitor and transmit information on external and internal Pi status remain to be elucidated in plants. This review summarizes molecular and developmental Pi starvation responses of higher plants and the evidence for coordinated regulation of gene expression, followed by a discussion of the potential involvement of plant hormones in Pi sensing and of molecular genetic approaches to elucidate plant signalling of low Pi availability. Complementary genetic strategies in Arabidopsis thaliana have been developed that are expected to identify components of plant signal transduction pathways involved in Pi sensing. Innovative screening methods utilize reporter gene constructs, conditional growth on organophosphates and the inhibitory properties of the Pi analogue phosphite, which hold the promise for significant advances in our understanding of the complex mechanisms by which plants regulate Pi-starvation responses. [source] The Regulation of Motile Activity in Fish ChromatophoresPIGMENT CELL & MELANOMA RESEARCH, Issue 5 2000RYOZO FUJII Chromatophores, including melanophores, xanthophores, erythrophores, leucophores and iridophores, are responsible for the revelation of integumentary coloration in fish. Recently, blue chromatophores, also called cyanophores, were added to the list of chromatophores. Many of them are also known to possess cellular motility, by which fish are able to change their integumentary hues and patterns, thus enabling them to execute remarkable or subtle chromatic adaptation to environmental hues and patterns, and to cope with various ethological encounters. Such physiological color changes are indeed crucial for them to survive, either by protecting themselves from predators or by increasing their chances of feeding. Sometimes, they are also useful in courtship and mutual communications among individuals of the same species, leading to an increased rate of species survival. Such strategies are realized by complex mechanisms existing in the endocrine and/or nervous systems. Current studies further indicate that some paracrine factors such as endothelins (ETs) are involved in these processes. In this review, the elaborate mechanisms regulating chromatophores in these lovely aquatic animals are described. [source] An optimum method designed for 2-D DIGE analysis of human arterial intima and media layers isolated by laser microdissectionPROTEOMICS - CLINICAL APPLICATIONS, Issue 10 2009Fernando de la Cuesta Abstract The formation and progression of atherosclerotic lesions involve complex mechanisms which are still not fully understood. A variety of cell types from the distinct arterial layers are implicated in the whole process from lipid accumulation within the vascular wall to plaque development and final rupture. In the present work, we employ the combination of laser microdissection and pressure catapulting and 2-D DIGE saturation labeling to investigate the human intima and media sub-proteomes isolated from atherosclerotic (coronary and aorta) or non-atherosclerotic vessels (preatherosclerotic coronary arteries). Laser microdissection and pressure catapulting allows the specific isolation of regions of interest. In turn, DIGE saturation labeling overcomes the limitation of extensive microdissection times to recover the protein amount required to perform comparative 2-DE, particularly when dealing with tissue regions rich in myofilament proteins, which result in low protein recovery. The compatibility and optimum performance of both techniques were investigated in detail, paying special attention to tissue staining and protein solubilization. Since scarce amount of protein obtained from microdissected tissue made it impossible to directly perform protein identification from 2-DE spots by MS, we performed in-solution digestion followed by LC-MS/MS analysis of total protein extracts from intima and media in order to get an overall picture of protein composition. Proteins so identified confirm the nature of the isolated regions. Finally, similar spot resolution on 2-D DIGE gels was obtained for the different human artery types (coronary, aorta) and studied layers (intima, media), setting the basis for future clinical comparative studies. [source] Hypothalamic input is required for development of normal numbers of thyrotrophs and gonadotrophs, but not other anterior pituitary cells in late gestation sheepTHE JOURNAL OF PHYSIOLOGY, Issue 4 2008Eva Szarek To evaluate the hypothalamic contribution to the development of anterior pituitary (AP) cells we surgically disconnected the hypothalamus from the pituitary (hypothalamo-pituitary disconnection, HPD) in fetal sheep and collected pituitaries 31 days later. Pituitaries (n= 6 per group) were obtained from fetal sheep (term = 147 ± 3 days) at 110 days (unoperated group) of gestation and at 141 days from animals that had undergone HPD or sham surgery at 110 days. Cells were identified by labelling pituitary sections with antisera against the six AP hormones. Additionally, we investigated the colocalization of glycoprotein hormones. The proportions of somatotrophs and corticotrophs were unchanged by age or HPD. Lactotrophs increased 80% over time, but the proportion was unaffected by HPD. Thyrotrophs, which were unaffected by age, increased 70% following HPD. Gonadotrophs increased with gestational age (LH+ cells 55%; FSH+ cells 19-fold), but this was severely attenuated by HPD. We investigated the possible existence of a reciprocal effect of HPD on multipotential glycoprotein-expressing cells. Co-expression of LH and TSH was extremely rare (< 1%) and unchanged over the last month of gestation or HPD. The increase of gonadotrophs expressing FSH only or LH and FSH was attenuated by HPD. Therefore, the proportions of somatotrophs, lactotrophs and corticotrophs are regulated independently of hypothalamic input in the late gestation fetal pituitary. In marked contrast, the determination of the thyrotroph and gonadotroph lineages over the same time period is subject to complex mechanisms involving hypothalamic factors, which inhibit differentiation and/or proliferation of thyrotrophs, but stimulate gonadotrophs down the FSH lineage. Development of a distinct population of gonadotrophs, expressing only LH, appears to be subject to alternative mechanisms. [source] | ||||||||||||||||||||||||||||||||||