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Complex Network (complex + network)
Selected AbstractsUnified QSAR & network-based computational chemistry approach to antimicrobials.JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2010Abstract In the previous work, we reported a multitarget Quantitative Structure-Activity Relationship (mt-QSAR) model to predict drug activity against different fungal species. This mt-QSAR allowed us to construct a drug,drug multispecies Complex Network (msCN) to investigate drug,drug similarity (González-Díaz and Prado-Prado, J Comput Chem 2008, 29, 656). However, important methodological points remained unclear, such as follows: (1) the accuracy of the methods when applied to other problems; (2) the effect of the distance type used to construct the msCN; (3) how to perform the inverse procedure to study species,species similarity with multidrug resistance CNs (mdrCN); and (4) the implications and necessary steps to perform a substructural Triadic Census Analysis (TCA) of the msCN. To continue the present series with other important problem, we developed here a mt-QSAR model for more than 700 drugs tested in the literature against different parasites (predicting antiparasitic drugs). The data were processed by Linear Discriminate Analysis (LDA) and the model classifies correctly 93.62% (1160 out of 1239 cases) in training. The model validation was carried out by means of external predicting series; the model classified 573 out of 607, that is, 94.4% of cases. Next, we carried out the first comparative study of the topology of six different drug,drug msCNs based on six different distances such as Euclidean, Chebychev, Manhattan, etc. Furthermore, we compared the selected drug,drug msCN and species,species mdsCN with random networks. We also introduced here the inverse methodology to construct species,species msCN based on a mt-QSAR model. Last, we reported the first substructural analysis of drug,drug msCN using Triadic Census Analysis (TCA) algorithm. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010 [source] Complex networks: two ways to be robust?ECOLOGY LETTERS, Issue 6 2002Carlos J. Melián Abstract Recent studies of biological networks have focused on the distribution of the number of links per node. However, the connectivity distribution does not uncover all the complexity of their topology. Here, we analyse the relation between the connectivity of a species and the average connectivity of its nearest neighbours in three of the most resolved community food webs. We compare the pattern arising with the one recently reported for protein networks and for a simple null model of a random network. Whereas two highly connected nodes are unlikely to be connected between each other in protein networks, the reverse happens in food webs. We discuss this difference in organization in relation to the robustness of biological networks to different types of perturbation. [source] Imaging of the lymphatic system: new horizons,CONTRAST MEDIA & MOLECULAR IMAGING, Issue 6 2006Tristan Barrett Abstract The lymphatic system is a complex network of lymph vessels, lymphatic organs and lymph nodes. Traditionally, imaging of the lymphatic system has been based on conventional imaging methods like computed tomography (CT) and magnetic resonance imaging (MRI), whereby enlargement of lymph nodes is considered the primary diagnostic criterion for disease. This is particularly true in oncology, where nodal enlargement can be indicative of nodal metastases or lymphoma. CT and MRI on their own are, however, anatomical imaging methods. Newer imaging methods such as positron emission tomography (PET), dynamic contrast-enhanced MRI (DCE-MRI) and color Doppler ultrasound (CDUS) provide a functional assessment of node status. None of these techniques is capable of detecting flow within the lymphatics and, thus, several intra-lymphatic imaging methods have been developed. Direct lymphangiography is an all-but-extinct method of visualizing the lymphatic drainage from an extremity using oil-based iodine contrast agents. More recently, interstitially injected intra-lymphatic imaging, such as lymphoscintigraphy, has been used for lymphedema assessment and sentinel node detection. Nevertheless, radionuclide-based imaging has the disadvantage of poor resolution. This has lead to the development of novel systemic and interstitial imaging techniques which are minimally invasive and have the potential to provide both structural and functional information; this is a particular advantage for cancer imaging, where anatomical depiction alone often provides insufficient information. At present the respective role each modality plays remains to be determined. Indeed, multi-modal imaging may be more appropriate for certain lymphatic disorders. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve diagnostic accuracy. Published in 2006 by John Wiley & Sons, Ltd. [source] Further extension of mammalian GATA-6DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 9 2005Masatomo Maeda Mammalian GATA-6, which has conserved tandem zinc fingers (CVNC-X17 -CNAC)-X29 -(CXNC-X17 -CNAC), is essential for the development and specific gene regulation of the heart, gastrointestinal tract and other tissues. GATA-6 recognizes the (A/T/C)GAT(A/T)(A) sequence, and interacts with other transcriptional regulators through its zinc-finger region. The mRNA of GATA-6 uses two Met codons in frame as translational initiation codons, and produces L- and S-type GATA-6 through leaky ribosome scanning. GATA-6 is subjected to cAMP-dependent proteolysis by a proteasome in a heterologous expression system. These protein-based characteristics of GATA-6 will be helpful for the identification of target genes, together with determination of the in vivo binding sites for GATA-6 and understanding of the complex network of gene regulation mediated by GATA-6. [source] Ooplasmic segregation in the zebrafish zygote and early embryo: Pattern of ooplasmic movements and transport pathwaysDEVELOPMENTAL DYNAMICS, Issue 8 2010Ricardo Fuentes Abstract Patterns of cytoplasmic movements and organization of transport pathways were examined in live or fixed zygotes and early zebrafish embryos using a variety of techniques. The zygote blastodisc grows by accumulation of ooplasm, transported to the animal pole from distinct sectors of ecto- and endoplasm at different speeds and developmental periods, using specific pathways or streamers. Slow transport (5 ,m/min) occurs during the first interphase along short streamers, whereas fast transport (9.6,40 ,m/min) takes place during the first cleavage division along axial and meridional streamers. Interconnections between streamers allow cargoes to change their speed and final destination. A similar sequence of events occurs during the following divisions. A complex network of microtubules and actin filaments in the endo- and ectoplasm appears to be involved in the transport of inclusions and mRNAs. Actin-dependent intermittent pulsations provoked high-speed back-and-forth movements of cytoplasm that may contribute to redistribution of organelles and maternal determinants. Developmental Dynamics 239:2172,2189, 2010. © 2010 Wiley-Liss, Inc. [source] The zebrafish bHLH PAS transcriptional regulator, single-minded 1 (sim1), is required for isotocin cell developmentDEVELOPMENTAL DYNAMICS, Issue 8 2006Jennifer L. Eaton Abstract A wide range of physiological and behavioral processes, such as social, sexual, and maternal behaviors, learning and memory, and osmotic homeostasis are influenced by the neurohypophysial peptides oxytocin and vasopressin. Disruptions of these hormone systems have been linked to several neurobehavioral disorders, including autism, Prader-Willi syndrome, affective disorders, and obsessive-compulsive disorder. Studies in zebrafish promise to reveal the complex network of regulatory genes and signaling pathways that direct the development of oxytocin- and vasopressin-like neurons, and provide insight into factors involved in brain disorders associated with disruption of these systems. Isotocin, which is homologous to oxytocin, is expressed early, in a simple pattern in the developing zebrafish brain. Single-minded 1 (sim1), a member of the bHLH-PAS family of transcriptional regulatory genes, is required for terminal differentiation of mammalian oxytocin cells and is a master regulator of neurogenesis in Drosophila. Here we show that sim1 is expressed in the zebrafish forebrain and is required for isotocin cell development. The expression pattern of sim1 mRNA in the embryonic forebrain is dynamic and complex, and overlaps with isotocin expression in the preoptic area. We provide evidence that the role of sim1 in zebrafish neuroendocrine cell development is evolutionarily conserved with that of mammals. Developmental Dynamics 235:2071,2082, 2006. © 2006 Wiley-Liss, Inc. [source] Pax3 and Dach2 positive regulation in the developing somiteDEVELOPMENTAL DYNAMICS, Issue 3 2002G. Kardon Abstract In vertebrates, skeletal muscles of the body arise from cells of somitic origin. Recently, somite culture experiments have identified a set of genes, including Pax3, Six1, Eya2, and Dach2, that appear to play an important role in early myogenesis during somite development (Heanue et al. [1999] Genes Dev. 13:3231,3243). In somite culture Pax3, Six1, Eya2, and Dach2 not only function to activate myogenesis, but they form a complex network regulating each other's transcription. We sought to examine whether this putative Pax3/Six1/Eya2/Dach2 network of regulation actually functions in vivo. In particular, we tested whether Pax3 and Dach2 participate in a positive regulatory feedback loop in vivo as they do in culture. To test in vivo Pax3/Dach2 interregulation, we took advantage of the known dependence of both factors on ectodermal signals. Somites isolated from the overlying ectoderm lose expression of Pax3 and Dach2. Therefore, we attempted to rescue Pax3 or Dach2 expression in somites isolated from the ectoderm by retroviral misexpression of the complementary factor. Indeed misexpression of Pax3 or Dach2 resulted in rescue of Dach2 or Pax3, respectively. These rescue experiments demonstrate that Pax3 and Dach2 positively regulate each other's expression in vivo and support the validity of the Pax3/Six1/Eya2/Dach 2 network in regulating myogenesis. © 2002 Wiley-Liss, Inc. [source] Cortical control of thermoregulatory sympathetic activationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2010M. Fechir Abstract Thermoregulation enables adaptation to different ambient temperatures. A complex network of central autonomic centres may be involved. In contrast to the brainstem, the role of the cortex has not been clearly evaluated. This study was therefore designed to address cerebral function during a whole thermoregulatory cycle (cold, neutral and warm stimulation) using 18-fluordeoxyglucose-PET (FDG-PET). Sympathetic activation parameters were co-registered. Ten healthy male volunteers were examined three times on three different days in a water-perfused whole-body suit. After a baseline period (32°C), temperature was either decreased to 7°C (cold), increased to 50°C (warm) or kept constant (32°C, neutral), thereafter the PET examination was performed. Cerebral glucose metabolism was increased in infrapontine brainstem and cerebellar hemispheres during cooling and warming, each compared with neutral temperature. Simultaneously, FDG uptake decreased in the bilateral anterior/mid-cingulate cortex during warming, and in the right insula during cooling and warming. Conjunction analyses revealed that right insular deactivation and brainstem activation appeared both during cold and warm stimulation. Metabolic connectivity analyses revealed positive correlations between the cortical activations, and negative correlations between these cortical areas and brainstem/cerebellar regions. Heart rate changes negatively correlated with glucose metabolism in the anterior cingulate cortex and in the middle frontal gyrus/dorsolateral prefrontal cortex, and changes of sweating with glucose metabolism in the posterior cingulate cortex. In summary, these results suggest that the cerebral cortex exerts an inhibitory control on autonomic centres located in the brainstem or cerebellum. These findings may represent reasonable explanations for sympathetic hyperactivity, which occurs, for example, after hemispheric stroke. [source] Glutamate receptor stimulation induces a persistent rhythmicity of the GABAergic inputs to rat midbrain dopaminergic neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2001Nicola Berretta Abstract The substantia nigra pars compacta and the ventral tegmental area are part of a complex network in the basal ganglia involved in behaviours as diverse as motor planning, generation of pleasure and drug addiction. Here we report that in the dopaminergic neurons of the rat ventral midbrain a brief coactivation of group I metabotropic and NMDA glutamate receptors may transform a temporally dispersed synaptic GABAergic input into a rhythmic pattern (range 4.5,22.5 Hz), probably through a mechanism involving electrotonic couplings. The plastic and long-lasting modification in the temporal code of the inhibitory synaptic activity induced by glutamate may be a key element in determining the function of midbrain dopaminergic neurons in both normal and pathological behaviour. [source] Histone modifications and chromatin dynamics: a focus on filamentous fungiFEMS MICROBIOLOGY REVIEWS, Issue 3 2008Gerald Brosch Abstract The readout of the genetic information of eukaryotic organisms is significantly regulated by modifications of DNA and chromatin proteins. Chromatin alterations induce genome-wide and local changes in gene expression and affect a variety of processes in response to internal and external signals during growth, differentiation, development, in metabolic processes, diseases, and abiotic and biotic stresses. This review aims at summarizing the roles of histone H1 and the acetylation and methylation of histones in filamentous fungi and links this knowledge to the huge body of data from other systems. Filamentous fungi show a wide range of morphologies and have developed a complex network of genes that enables them to use a great variety of substrates. This fact, together with the possibility of simple and quick genetic manipulation, highlights these organisms as model systems for the investigation of gene regulation. However, little is still known about regulation at the chromatin level in filamentous fungi. Understanding the role of chromatin in transcriptional regulation would be of utmost importance with respect to the impact of filamentous fungi in human diseases and agriculture. The synthesis of compounds (antibiotics, immunosuppressants, toxins, and compounds with adverse effects) is also likely to be regulated at the chromatin level. [source] TENDING CULTURAL LANDSCAPES AND FOOD CITIZENSHIP IN TORONTO'S COMMUNITY GARDENS,GEOGRAPHICAL REVIEW, Issue 3 2004LAUREN E. BAKER ABSTRACT. Scattered throughout the city of Toronto are more than no community gardens, sites of place-based politics connected to the community food-security movement. The gardens, spaces where passions for plants and food are shared, reflect the city's shifting cultural landscape and represent an everyday activity that is imbued with multiple meanings. Toronto's community food-security movement uses gardens as one strategy to regenerate the local food system and provide access to healthy, affordable food. Three garden case studies expand on the complexities of "food citizenship," illustrating the importance of that concept to notions of food security. The gardens reveal the role gardeners play in transforming urban spaces, the complex network of organizations working cooperatively and in partnership to implement these projects, and the way in which social and cultural pluralism are shaping the urban landscape. [source] Neural substrates of tactile object recognition: An fMRI studyHUMAN BRAIN MAPPING, Issue 4 2004Catherine L. Reed Abstract A functional magnetic resonance imaging (fMRI) study was conducted during which seven subjects carried out naturalistic tactile object recognition (TOR) of real objects. Activation maps, conjunctions across subjects, were compared between tasks involving TOR of common real objects, palpation of "nonsense" objects, and rest. The tactile tasks involved similar motor and sensory stimulation, allowing higher tactile recognition processes to be isolated. Compared to nonsense object palpation, the most prominent activation evoked by TOR was in secondary somatosensory areas in the parietal operculum (SII) and insula, confirming a modality-specific path for TOR. Prominent activation was also present in medial and lateral secondary motor cortices, but not in primary motor areas, supporting the high level of sensory and motor integration characteristic of object recognition in the tactile modality. Activation in a lateral occipitotemporal area associated previously with visual object recognition may support cross-modal collateral activation. Finally, activation in medial temporal and prefrontal areas may reflect a common final pathway of modality-independent object recognition. This study suggests that TOR involves a complex network including parietal and insular somatosensory association cortices, as well as occipitotemporal visual areas, prefrontal, and medial temporal supramodal areas, and medial and lateral secondary motor cortices. It confirms the involvement of somatosensory association areas in the recognition component of TOR, and the existence of a ventrolateral somatosensory pathway for TOR in intact subjects. It challenges the results of previous studies that emphasize the role of visual cortex rather than somatosensory association cortices in higher-level somatosensory cognition. Hum. Brain Mapping 21:236,246, 2004. © 2004 Wiley-Liss, Inc. [source] Ubiquitin protein modification and signal transduction: Implications for inflammatory bowel diseasesINFLAMMATORY BOWEL DISEASES, Issue 12 2005Cormac Taylor PhD Abstract A dysregulated immune response to luminal antigen(s) is associated with the development of inflammatory bowel diseases (IBDs). A complex network of inflammatory and immune mediators released by immune and nonimmune cells participate in the physiopathology of IBD. At the molecular level, events leading to the improper use of the signaling grid are likely responsible for the dysregulated activation of various transcription factors and subsequent induction of inflammatory genes. The posttranslational modification of signaling proteins by the ubiquitin system is a critical event in activation or repression of transcription factors. Two important transcriptional pathways in which ubiquitin is central are the nuclear factor-,B and hypoxia inducible factor-1 (HIF-1) pathways, both of which are important components of intestinal homeostasis. In this review, we discuss the role of ubiquitin modification in relation to nuclear factor-,B and HIF-1 signaling and consider its impact on intestinal inflammation. A greater understanding of posttranslational ubiquitin modification may lead to the identification of new therapeutic opportunities for the treatment of IBD. [source] Mechanisms and modulation of intestinal epithelial repairINFLAMMATORY BOWEL DISEASES, Issue 1 2001Dr. Axel U. Dignass Abstract The mucosal epithelium of the alimentary tract represents a crucial barrier to a broad spectrum of noxious and immunogenic substances within the intestinal lumen. An impairment of the integrity of the mucosal epithelial barrier is observed in the course of various intestinal disorders including inflammatory bowel diseases (IBD), celiac disease, intestinal infections, and various other diseases. Furthermore, even under physiologic conditions temporary damage of the epithelial surface mucosa may be caused by proteases, residential flora, dietary compounds, or other factors. Generally, the integrity of the intestinal mucosal surface barrier is rapidly reestablished even after extensive destruction because of an enormous regenerative capability of the mucosal surface epithelium. Rapid resealing of the surface epithelium is accomplished by epithelial cell migration, also termed epithelial restitution, epithelial cell proliferation, and differentiation. Healing of the intestinal surface epithelium is regulated by a complex network of highly divergent factors, among them a broad spectrum of structurally distinct regulatory peptides that have been identified within the mucosa of the intestinal tract. These regulatory peptides, conventionally designated as growth factors and cytokines, play an essential role in regulating differential epithelial cell functions to preserve normal homeostasis and integrity of the intestinal mucosa. In addition, a number of other peptide molecules such as extracellular matrix factors and blood clotting factors, and also nonpeptide molecules including phospholipids, short-chain fatty acids, adenine nucleotides, trace elements, and pharmacological agents, have been demonstrated to modulate intestinal epithelial repair mechanisms. Some of these molecules may be released by platelets, adjacent stromal cells, inflammatory cells, or injured epithelial and nonepithelial cells and may play an important role in the modulation of intestinal injury. Repeated damage and injury of the intestinal surface are key features of various intestinal disorders including IBD and require constant repair of the epithelium. Enhancement of intestinal repair mechanisms by regulatory peptides or other modulatory factors may provide future approaches for the treatment of diseases that are characterized by injuries of the epithelial surface. [source] Unraveling the Role of Mitochondria During Oxidative Stress in PlantsIUBMB LIFE, Issue 4 2001Harvey Millar Abstract The sedentary habit of plants means that they must stand and fight environmental stresses that their mobile animal cousins can avoid. A range of these abiotic stresses initiate the production in plant cells of reactive oxygen and nitrogen species that ultimately lead to oxidative damage affecting the yield and quality of plant products. A complex network of enzyme systems, producing and quenching these reactive species operate in different organelles. It is the integration of these compartmented defense systems that coordinates an effective response to the various stresses. Future attempts to improve plant growth or yield must consider the complexity of inter-organelle signaling and protein targeting if they are to be successful in producing plants with resistance to a broad range of stresses. Here we highlight the role of pre-oxidant, anti-oxidant, and post-oxidant defense systems in plant mitochondria and the potential role of proteins targeted to both mitochondria and chloroplasts, in an integrated defense against oxidative damage in plants. [source] Intolerable human suffering and the role of the ancestor: literary criticism as a means of analysisJOURNAL OF ADVANCED NURSING, Issue 3 2000Elizabeth Harrison RN PhD Intolerable human suffering and the role of the ancestor: literary criticism as a means of analysis This essay explores the experience of intolerable human suffering in Toni Cade Bambara's novel, The Salt Eaters. The method of analysis is literary criticism, a technique that shares many of the same goals as other types of inquiry. It employs close reading to illuminate the novel's meaning(s), thereby revealing information about the nature of intolerable human suffering. Morrison's characteristics of black art is the literary and cultural framework that guides the analysis of Bambara's novel. The paradigm has broad application for nursing. The purpose of this analysis was to describe the role of the ancestral system as a predictor of the trajectory of suffering. The results extend Morrison's paradigm and her notion of ancestor to include traditions and other non-corporeal factors that are essential for well-being and survival. The protagonist in Bambara's novel, Velma Henry, is the patient and exemplar who does not succumb to intolerable suffering because of its cumulative weight, but because she has lost touch with the traditions of her people, an essential component of her ancestral system. The ancestral system is a rich and complex network of individuals, groups, customs and beliefs that are instructive, protective and benevolent. Ancestors are also timeless and provide wisdom, but when the ancestral system is weak or absent, the trajectory of suffering is not favourable. Nurses must learn to recognize intolerable human suffering, to identify the patient's ancestral system, and to work within that system to keep suffering patients from harm. [source] From neuroanatomy to gene therapy: searching for new ways to manipulate the supraspinal endogenous pain modulatory systemJOURNAL OF ANATOMY, Issue 2 2007I. Tavares Abstract The endogenous pain modulatory system is a complex network of brain areas that control nociceptive transmission at the spinal cord by inhibitory and facilitatory actions. The balance between these actions ensures effective modulation of acute pain, while during chronic pain the pronociceptive effects appear to prevail. The mechanisms underlying this imbalance were studied as to the role of two medullary components of the pain modulatory system: the dorsal reticular nucleus and the caudal ventrolateral medulla, which function primarily as pronociceptive and antinociceptive centres, respectively. Both areas are connected with the spinal dorsal horn by closed reciprocal loops. In the spino-dorsal reticular nucleus loop, the ascending branch is strongly inhibited by spinal GABAergic neurons, which may act as a buffering system of the dorsal reticular nucleus-centred amplifying effect. In the spino-caudal ventrolateral medulla loop, the ascending branch is under potent excitation of substance P (SP) released from primary afferents, which is likely to trigger the intense descending inhibition detected in acute pain. During chronic pain, the activity in the lateral reticular formation of the caudal ventrolateral medulla changes, so that the action of the caudal ventrolateral medulla upon SP-responsive spinal neurons shifts from inhibitory to excitatory. The mechanisms of this modulatory shift are unknown but probably relate to the decresed expression of µ-opioid, ,-opioid and GABAB receptors. Normalizing receptor expression in the caudal ventrolateral medulla or controlling noci-evoked activity at the dorsal reticular nucleus or caudal ventrolateral medulla by interfering with neurotransmitter release is now possible by the use of gene therapy, an approach that stands out as a unique tool to manipulate the supraspinal endogenous pain control system. [source] AKT1 leader gene and downstream targets are involved in a rat model of kidney allograft tolerance,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 3 2010Vojislav Jovanovic Abstract Tolerance is the so-called "Holy Grail" of transplantation but achieving this state is proving a major challenge, particularly in the clinical settings. This tolerance state can be induced in rodent models using a variety of maneuvers. This phenomenon is classically characterized by donor specificity (recipients accept a secondary donor-specific allograft but reject third-party allograft) as well as by the absence of chronic rejection lesion. We previously showed that administration and anti-donor anti-class II serum on the day of transplantation induce tolerance to a kidney allograft in the LEW-1W to LEW-1A strain combination. In this study, we used DNA microarrays to compare gene patterns involved in anti-donor anti-class II tolerated or untreated syngeneic kidney transplants in this strain combination. Statistical and non-statistical analyses were combined with ab initio analysis, using the recently developed leader gene approach, to shed new light on this phenomenon. Theoretical and experimental results suggest that tolerance and rejection outcome may be in large part determined by low expression variations of some genes, which can form a core gene network around specific genes such as Rac1, NFKB1, RelA, AKT1, IKBKB, BCL2, BCLX, and CHUK. Through this model, we showed that AKT1 gene, WNT pathway and NO synthesis are strictly connected to each other and may play an important role in kidney tolerance and rejection processes, with AKT1 gene being the center of this complex network of interactions. J. Cell. Biochem. 111: 709,719, 2010. © 2010 Wiley-Liss, Inc. [source] Neutrophil apoptosis: A target for enhancing the resolution of inflammationJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 5 2009János G. Filep Abstract Neutrophils are essential for host defense and their programmed cell death and removal are critical for the optimal expression as well as for efficient resolution of inflammation. Delayed neutrophil apoptosis or impaired clearance of apoptotic neutrophils by macrophages contributes to the progression of chronic inflammation. Under most conditions, neutrophils are exposed to multiple factors and their fate would ultimately depend on the balance between pro-survival and pro-apoptotic signals. Life or death decisions are tightly controlled by a complex network of intracellular signaling pathways. Accumulating data indicate that receptors, such as the formyl peptide receptor 2/lipoxin receptor or ,2 -integrins can generate contrasting cues in neutrophils in a ligand-specific manner and suggest a hierarchy among these signals. In this article, we review recent advances on how pro-apoptosis and pro-survival signals interact to determine the fate of neutrophils and the inflammatory response, and highlight novel pharmacological strategies that could be used to enhance the resolution of inflammation by redirecting neutrophils to apoptosis. J. Cell. Biochem. 108: 1039,1046, 2009. © 2009 Wiley-Liss, Inc. [source] CXCL12 chemokine up-regulates bone resorption and MMP-9 release by human osteoclasts: CXCL12 levels are increased in synovial and bone tissue of rheumatoid arthritis patientsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004Francesco Grassi Chemokines are involved in a number of inflammatory pathologies and some of them show a pivotal role in the modulation of osteoclast development. Therefore, we evaluated the role of CXCL12 chemokine on osteoclast differentiation and function and we analyzed its expression on synovial and bone tissue biopsies from rheumatoid arthritis (RA) patients. Osteoclasts were obtained by 7 days in vitro differentiation with RANKL and M-CSF of CD11b positive cells in the presence or absence of CXCL12. The total number of osteoclast was analyzed by Tartrate-resistant acid phosphatase (TRAP)-staining and bone-resorbing activity was assessed by pit assay. MMP-9 and TIMP-1 release was evaluated by ELISA assay. CXCL12 expression on biopsies from RA patients was analyzed by immunohistochemistry. Osteoclasts obtained in the presence of CXCL12 at 10 nM concentration displayed a highly significant increase in bone-resorbing activity as measured by pit resorption assay, while the total number of mature osteoclasts was not affected. The increased resorption is associated with overexpression of MMP-9. Immunostaining for CXCL12 on synovial and bone tissue biopsies from both rheumatoid arthritis (RA) and osteoarthritis (OA) samples revealed a strong increase in the expression levels under inflammatory conditions. CXCL12 chemokine showed a clear activating role on mature osteoclast by inducing bone-resorbing activity and specific MMP-9 enzymatic release. Moreover, since bone and synovial biopsies from RA patients showed an elevated CXCL12 expression, these findings may provide useful tools for achieving a full elucidation of the complex network that regulates osteoclast function in course of inflammatory diseases. J. Cell. Physiol. 199: 244,251, 2004© 2003 Wiley-Liss, Inc. [source] An islet in distress: , cell failure in type 2 diabetesJOURNAL OF DIABETES INVESTIGATION, Issue 4 2010Takeshi Ogihara Abstract Over 200 million people worldwide suffer from diabetes, a disorder of glucose homeostasis. The majority of these individuals are diagnosed with type 2 diabetes. It has traditionally been thought that tissue resistance to the action of insulin is the primary defect in type 2 diabetes. However, recent longitudinal and genome-wide association studies have shown that insulin resistance is more likely to be a precondition, and that the failure of the pancreatic , cell to meet the increased insulin requirements is the triggering factor in the development of type 2 diabetes. A major emphasis in diabetes research has therefore shifted to understanding the causes of , cell failure. Collectively, these studies have implicated a complex network of triggers, which activate intersecting execution pathways leading to , cell dysfunction and death. In the present review, we discuss these triggers (glucotoxicity, lipotoxicity, amyloid and cytokines) with respect to the pathways they activate (oxidative stress, inflammation and endoplasmic reticulum stress) and propose a model for understanding , cell failure in type 2 diabetes. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00021.x, 2010) [source] Improving the performance of natural gas pipeline networks fuel consumption minimization problemsAICHE JOURNAL, Issue 4 2010F. Tabkhi Abstract As the gas industry has developed, gas pipeline networks have evolved over decades into very complex systems. A typical network today might consist of thousands of pipes, dozens of stations, and many other devices, such as valves and regulators. Inside each station, there can be several groups of compressor units of various vintages that were installed as the capacity of the system expanded. The compressor stations typically consume about 3,5% of the transported gas. It is estimated that the global optimization of operations can save considerably the fuel consumed by the stations. Hence, the problem of minimizing fuel cost is of great importance. Consequently, the objective is to operate a given compressor station or a set of compressor stations so that the total fuel consumption is reduced while maintaining the desired throughput in the line. Two case studies illustrate the proposed methodology. Case 1 was chosen for its simple and small-size design, developed for the sake of illustration. The implementation of the methodology is thoroughly presented and typical results are analyzed. Case 2 was submitted by the French Company Gaz de France. It is a more complex network containing several loops, supply nodes, and delivery points, referred as a multisupply multidelivery transmission network. The key points of implementation of an optimization framework are presented. The treatment of both case studies provides some guidelines for optimization of the operating performances of pipeline networks, according to the complexity of the involved problems. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Apoptosis-associated gene expression in HIV-infected patients in response to successful antiretroviral therapy,JOURNAL OF MEDICAL VIROLOGY, Issue 2 2007Emanuela Balestrieri Abstract The simultaneous expression of 19 apoptosis-related genes was analyzed by RNA-protection assay in peripheral blood mononuclear cells of HIV-infected patients before and during successful antiretroviral therapy (ART). After 12 months of therapy, the expression of the pro-apoptotic genes FAS, FAS-L, FAF-1, FADD, CASPASE-8, DR3, TRAIL, TNFR-1, TRADD, and BAX was significantly downregulated with respect to time 0, while that of BCL-2, BCL-XL, and MCL-1 was significantly upregulated. The data suggest that inhibition of cell death in HIV-positive patients under successful therapy is the result of a complex network of multifactor signaling, correlated with both death and survival of lymphocytes. J. Med. Virol. 79:111,117, 2007. © 2006 Wiley-Liss, Inc. [source] Three-dimensional reconstruction and neural map of the serotonergic brain of Asplanchna brightwellii (Rotifera, Monogononta)JOURNAL OF MORPHOLOGY, Issue 4 2009Rick Hochberg Abstract The basic organization of the rotifer brain has been known for nearly a century; yet, fine details on its structure and organization remain limited despite the importance of rotifers in studies of evolution and population biology. To gain insight into the structure of the rotifer brain, and provide a foundation for future neurophysiologic and neurophylogenetic research, the brain of Asplanchna brightwellii was studied with immunohistochemistry, confocal laser scanning microscopy, and computer modeling. A three-dimensional map of serotonergic connections reveals a complex network of approximately 28 mostly unipolar, cerebral perikarya and associated neurites. Cells and their projections display symmetry in quantity, size, connections, and pathways between cerebral hemispheres within and among individuals. Most immunopositive cells are distributed close to the brain midline. Three pairs of neurites form decussations at the brain midline and may innervate sensory receptors in the corona. A single neuronal pathway appears to connect both the lateral horns and dorsolateral apical receptors, suggesting that convergence of synaptic connections may be common in the afferent sensory systems of rotifers. Results show that the neural map of A. brightwellii is much more intricate than that of other monogonont rotifers; nevertheless, the consistency in neural circuits provides opportunities to identify homologous neurons, distinguish functional regions based on neurotransmitter phenotype, and explore new avenues of neurophylogeny in Rotifera. J. Morphol. 2009. © 2008 Wiley-Liss, Inc. [source] Cyclic guanosine monophosphate signalling pathway plays a role in neural cell adhesion molecule-mediated neurite outgrowth and survivalJOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2007Dorte Kornerup Ditlevsen Abstract The neural cell adhesion molecule (NCAM) plays a crucial role in neuronal development, regeneration, and synaptic plasticity associated with learning and memory consolidation. Homophilic binding of NCAM leads to neurite extension and neuroprotection in various types of primary neurons through activation of a complex network of signalling cascades, including fibroblast growth factor receptor, Src-family kinases, the mitogen-activated protein kinase pathway, protein kinase C, phosphatidylinositol-3 kinase, and an increase in intracellular Ca2+. Here we present data indicating an involvement of cyclic GMP in NCAM-mediated neurite outgrowth in both hippocampal and dopaminergic neurons and in NCAM-mediated neuroprotection of dopaminergic neurons. In addition, evidence is presented suggesting that NCAM mediates activation of cGMP via synthesis of nitric oxide (NO) by NO synthase (NOS) and activation of soluble guanylyl cyclase by NO, leading to an increased synthesis of cGMP and activation by cGMP of protein kinase G. © 2007 Wiley-Liss, Inc. [source] PATTERNS OF INTERSPECIFIC INTERACTIONS IN THE ULVA -DOMINATED INTERTIDAL COMMUNITY IN A SOUTHERN COAST OF KOREAJOURNAL OF PHYCOLOGY, Issue 2000Y.J. Bhang In the southern coast of Korea, rocky intertidal zones where green tide commonly occurs are dominated by Ulva pertusa, red algal turf (a mixed stand of Gigartina intermedia and Gigartina teedii) and species of Enteromorpha with highly opportunistic occurrence. To investigate their interspecific interactions, a field experiment was carried out using press effect of one species removal from permanent plots (20 x 20cm) set up on two different tidal heights. Mechanisms of interaction were also attempted using artificial plants to test the possible effects of shading, scouring, allelopathy of U. pertusa on the turf algae. The turf-forming red algae lowered the abundance of U. pertusa presumably by inhibiting the recruitment of U. pertusa; this effect was consistent along the tidal height. However, the greater abundance of Enteromorpha was observed in the presence of turf in the upper zone, indicating a positive effect of turf on Enteromorpha. Once U. pertusa was successfully recruited and grown to the adult plant, it inhibited the growth of turf by shading, which was effective both in winter and summer regardless of desiccation stress. No scouring and allelopathic effects of U. pertusa on the turf were detected. When an open substrate was provided, Enteromorpha colonized the space faster than any other species in the upper zone, but the turf was the fastest one followed by U. pertusa and Enteromorpha in the lower zone. Results indicated that patterns of interaction represented a complex network with no ultimate winner and the outcomes of interaction varied over time and space. [source] A physical organic mechanistic approach to understanding the complex reaction network of hemostasis (blood clotting)JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 10 2007Christian J. Kastrup Abstract This review focuses on how the mechanistic approach of physical organic chemistry can be used to elucidate the mechanisms behind complex biochemical networks. The dynamics of biochemical reaction networks is difficult to describe by considering their individual reactions, just as the dynamics of organic reactions is difficult to describe by considering individual electrons and atomic nuclei. Physical organic chemists have developed a useful set of tools to predict the outcome of organic reactions by separating the interacting molecules into modules (functional groups), and defining general rules for how these modules interact (mechanisms). This review shows how these tools of physical organic chemistry may be used to describe reaction networks. In addition, it describes the application of these tools to develop a mechanistic understanding of the dynamics of the complex network of hemostasis, which regulates blood clotting. Copyright © 2007 John Wiley & Sons, Ltd. [source] Science and culture around the Montessori's first "Children's Houses" in Rome (1907,1915)JOURNAL OF THE HISTORY OF THE BEHAVIORAL SCIENCES, Issue 3 2008Renato Foschi Between 1907 and 1908, Maria Montessori's (1870,1952) educational method was elaborated at the Children's Houses of the San Lorenzo district in Rome. This pioneering experience was the basis for the international fame that came to Montessori after the publication of her 1909 volume dedicated to her "Method." The "Montessori Method" was considered by some to be scientific, liberal, and revolutionary. The present article focuses upon the complex contexts of the method's elaboration. It shows how the Children's Houses developed in relation to a particular scientific and cultural eclecticism. It describes the factors that both favored and hindered the method's elaboration, by paying attention to the complex network of social, institutional, and scientific relationships revolving around the figure of Maria Montessori. A number of "contradictory" dimensions of Montessori's experience are also examined with a view to helping to revise her myth and offering the image of a scholar who was a real early-twentieth-century prototype of a "multiple" behavioral scientist. © 2008 Wiley Periodicals, Inc. [source] Developmental regulation of the glyoxylate cycle in the human pathogen Penicillium marneffeiMOLECULAR MICROBIOLOGY, Issue 6 2006David Cánovas Summary Penicillium marneffei is a thermally dimorphic opportunistic human pathogen with a saprophytic filamentous hyphal form at 25°C and a pathogenic unicellular yeast form at 37°C. During infection. P. marneffei yeast cells exist intracellularly in macrophages. To cope with nutrient deprivation during the infection process, a number of pathogens employ the glyoxylate cycle to utilize fatty acids as carbon sources. The genes which constitute this pathway have been implicated in pathogenesis. To investigate acetate and fatty acid utilization, the acuD gene encoding a key glyoxylate cycle enzyme (isocitrate lyase) was cloned. The acuD gene is regulated by both carbon source and temperature in P. marneffei, being strongly induced at 37°C even in the presence of a repressing carbon source such as glucose. When introduced into the non-pathogenic monomorphic fungus Aspergillus nidulans, the P. marneffei acuD promoter only responds to carbon source. Similarly, when the A. nidulans acuD promoter is introduced into P. marneffei it only responds to carbon source suggesting that P. marneffei possesses both cis elements and trans -acting factors to control acuD by temperature. The Zn(II)2Cys6 DNA binding motif transcriptional activator FacB was cloned and is responsible for carbon source-, but not temperature-, dependent induction of acuD. The expression of acuD at 37°C is induced by AbaA, a key regulator of morphogenesis in P. marneffei, but deletion of abaA does not completely eliminate temperature-dependent induction, suggesting that acuD and the glyoxylate cycle are regulated by a complex network of factors in P. marneffei which may contribute to its pathogenicity. [source] Roles of CmpR, a LysR family transcriptional regulator, in acclimation of the cyanobacterium Synechococcus sp. strain PCC 7942 to low-CO2 and high-light conditionsMOLECULAR MICROBIOLOGY, Issue 3 2004Yukari Takahashi Summary The cmp operon of Synechococcus sp. strain PCC 7942, encoding a high-affinity bicarbonate transporter, is induced under low CO2 conditions by a LysR family protein CmpR. CmpR was found to be required also for induction of the operon by transfer of the cells from low-light to high-light conditions, indicating involvement of a common mechanism in the high-light- and low-CO2 -responsive regulation. Expression of the high-light inducible genes psbAII and psbAIII, on the other hand, was found to be induced also by low-CO2 conditions. A single promoter was responsible for the high-light and low-CO2 induction of each of psbAII and psbAIII, suggesting involvement of a common regulatory mechanism in the light and CO2 responses of the psbA genes. CmpR was, however, not required for the induction of psbAII and psbAIII, indicating the presence of multiple mechanisms for induction of genes under high-light and low-CO2 conditions. The CmpR-deficient mutant nevertheless showed lower levels of the psbAII and psbAIII transcripts than the wild-type strain under all the light and CO2 conditions examined. Gel shift assays showed that CmpR binds to the enhancer elements of psbAII and psbAIII, through specific interaction with a sequence signature conforming to the binding motif of similar LysR family proteins. These findings showed that CmpR acts as a trans -acting factor that enhances transcription of the photosystem II genes involved in acclimation to high light, revealing a complex network of gene regulation in the cyanobacterium. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||