523 research outputs found

    Are riparian buffers surrounding forestry-impacted streams sufficient to meet key ecological objectives? A Swedish case study

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    In many national guidelines and policies regarding protection of freshwater systems from stressors associated with forestry, riparian buffer width is a commonly prescribed strategy, typically with no other refinements of protection measures. In Sweden, the Strategic Management Objectives (SMOs) were developed to ensure that riparian buffers that are left after harvesting sustain important ecosystem attributes in aquatic systems, referred to as objectives, namely shading, biodiversity, reduction of sedimentation, and provision of deadwood and food. However, little specification is given on threshold targets or how to manage riparian zones to effectively provide these objectives. In this paper, we evaluated whether existing riparian buffers of different widths along small, recently harvested (<8 years) streams were able to provide proxies of these targeted objectives, and further compared harvested streams to counterparts situated in mature unharvested production forests (reference) in northern and southern Sweden. The influence of buffer width varied with objective and geographic location. In both regions, canopy cover (proxy for shading) increased with riparian width, and riparian deadwood was highest in no buffer sites. Organic matter (OM; proxy for food) was highest in the northern no buffer streams, while in the south OM increased with buffer width. All other parameters tested had no relationship to buffer width. These differing responses even in streams subjected to similar land-use and management within a close vicinity and region, suggest that the contemporary strategy of prescribing fixed buffer widths and/or stating objectives without defined guidelines for what constitutes an effective riparian buffer is insufficient given the large variability of stream ecosystems across small spatial scales. More comprehensive consideration synergistically accounting for site-specificity and land mosaic planning are needed to develop functionally effective buffers that can mitigate forestry impacts on stream ecosystems

    Fluorinated Porphyrinic Crystalline Solids: Structural Elucidation and Study of Intermolecular Interactions

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    Crystal engineering is an emerging area of research in material, biological, and pharmaceutical chemistry that involves synthesis of new materials, analysis of its structure including intermolecular interactions using X‐ray crystallography as well as computational methods. It has been shown that the intermolecular interactions involving organic fluorine such as C−F∙∙∙H, F∙∙∙F, and C−F∙∙∙π play an important role in stabilizing the supramolecular assemblies, especially in the absence of strong intermolecular forces. Recently, non‐covalent interactions involving conjugated aromatic system such as porphyrins have been studied intensively. The synthetic porphyrins are of widespread attention because of their close resemblance to naturally occurring tetrapyrrolic pigments and they find various materials and biological applications. In this book chapter, we disclose our recent findings on detailed crystal structure analysis of a few series of fluorinated porphyrins using single‐crystal XRD as well as computational Hirshfeld surface analysis to understand the role of close contacts involving fluorine in the molecular crystal packing

    Dramatic inhibition of osteoclast sealing ring formation and bone resorption in vitro by a WASP-peptide containing pTyr294 amino acid

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    Wiskott Aldrich Syndrome protein (WASP) has a unique regulatory role in sealing ring formation and bone resorption in osteoclasts. Here, using the TAT-transduction method, we show the possible role of WASP domain(s) in sealing ring formation and bone resorption. Transduction of TAT-fused full-length WASP peptide induced Arp2/3 complex formation, F-actin content, sealing ring formation and bone resorption. Transduction of WASP peptides containing basic, verpolin-central, pTyr294, and proline-rich regions inhibited the processes listed above at various levels. The ability to resorb bone by WASP peptides containing basic, verpolin-central, and proline-rich regions was reduced and the resorbed area matched the size of the sealing ring. However, osteoclasts transduced with WASP peptide containing pTyr294aa demonstrated the following: a) a considerable decrease in the interaction and phosphorylation of c-Src with endogenous WASP; b) total loss of sealing ring-like structures; c) formation of actin-rich patches at the peripheral edge that contains filopodia-like projections; d) reduced capacity for bone resorption in vitro. These findings suggest that modulation of phosphorylation state of pTyr294aa assists in integrating multiple signaling molecule and pathways that partake in the assembly of sealing ring

    Integrin αvÎČ3 and CD44 pathways in metastatic prostate cancer cells support osteoclastogenesis via a Runx2/Smad 5/receptor activator of NF-ÎșB ligand signaling axis

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    BACKGROUND: Bone loss and pathological fractures are common skeletal complications associated with androgen deprivation therapy and bone metastases in prostate cancer patients. We have previously demonstrated that prostate cancer cells secrete receptor activator of NF-kB ligand (RANKL), a protein essential for osteoclast differentiation and activation. However, the mechanism(s) by which RANKL is produced remains to be determined. The objective of this study is to gain insight into the molecular mechanisms controlling RANKL expression in metastatic prostate cancer cells. RESULTS: We show here that phosphorylation of Smad 5 by integrin αvÎČ3 and RUNX2 by CD44 signaling, respectively, regulates RANKL expression in human-derived PC3 prostate cancer cells isolated from bone metastasis. We found that RUNX2 intranuclear targeting is mediated by phosphorylation of Smad 5. Indeed, Smad5 knock-down via RNA interference and inhibition of Smad 5 phosphorylation by an αv inhibitor reduced RUNX2 nuclear localization and RANKL expression. Similarly, knockdown of CD44 or RUNX2 attenuated the expression of RANKL. As a result, conditioned media from these cells failed to support osteoclast differentiation in vitro. Immunohistochemistry analysis of tissue microarray sections containing primary prostatic tumor (grade2-4) detected predominant localization of RUNX2 and phosphorylated Smad 5 in the nuclei. Immunoblotting analyses of nuclear lysates from prostate tumor tissue corroborate these observations. CONCLUSIONS: Collectively, we show that CD44 signaling regulates phosphorylation of RUNX2. Localization of RUNX2 in the nucleus requires phosphorylation of Smad-5 by integrin αvÎČ3 signaling. Our results suggest possible integration of two different pathways in the expression of RANKL. These observations imply a novel mechanistic insight into the role of these proteins in bone loss associated with bone metastases in patients with prostate cancer

    Mechanisms of osteopontin and CD44 as metastatic principles in prostate cancer cells

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    BACKGROUND: The expression level of osteopontin correlates with the metastatic potential of several tumors. Osteopontin is a well-characterized ligand for the αvÎČ3 integrin. The present study was undertaken to elucidate the possible role of osteopontin/αvÎČ3 signaling in prostate cancer cell migration. RESULTS: We generated stable prostate cancer cell (PC3) lines that over-express osteopontin (PC3/OPN), mutant OPN in the integrin binding-site (PC3/RGDΔRGA), and null for OPN (PC3/SiRNA). The following observations were made in PC3/OPN cells as compared with PC3 cells: 1) an increase in multinucleated giant cells and RANKL expression; 2) an increase in CD44 surface expression, interaction of CD44/MMP-9 on the cell surface, MMP-9 activity in the conditioned medium, and cell migration; 3) western blot analysis of concentrated conditioned medium exhibited equal levels of MMP-9 protein in all PC3 cells. However, zymography analysis demonstrated that the levels of MMP-9 activity in the conditioned media reflect the CD44 surface expression pattern of the PC3 cell lines; 4) although MMP-9 and MMP-2 are secreted by PC3 cells, only the secretion of MMP-9 is regulated by OPN expression. A strong down regulation of the above-mentioned processes was observed in PC3/OPN (RGA) and PC3/SiRNA cells. PC3/OPN cells treated with bisphosphonate (BP) reproduce the down-regulation observed in PC3/OPN (RGA) and PC3/SiRNA cells. CONCLUSION: Rho signaling plays a crucial role in CD44 surface expression. BPs inhibits the mevalonate pathway, which in turn, prevents the prenylation of a number of small GTPases. Attenuation of Rho GTPase activation by BPs may have contributed to the down regulation of cell surface CD44/MMP-9 interaction, MMP-9 activation/secretion, and cell migration. Taken together, these observations suggest that CD44 surface expression is an important event in the activation of MMP-9 and migration of prostate cancer cells. The various steps involved in the above mentioned signaling pathway and/or the molecules regulating the activation of MMP-9 are potential therapeutic target

    Medicinal plants used by traditional healers in Kancheepuram District of Tamil Nadu, India

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    An ethnobotanical survey was undertaken to collect information from traditional healers on the use of medicinal plants in Kancheepuram district of Tamil Nadu during October 2003 to April 2004. The indigenous knowledge of local traditional healers and the native plants used for medicinal purposes were collected through questionnaire and personal interviews during field trips. The investigation revealed that, the traditional healers used 85 species of plants distributed in 76 genera belonging to 41 families to treat various diseases. The documented medicinal plants were mostly used to cure skin diseases, poison bites, stomachache and nervous disorders. In this study the most dominant family was Euphorbiaceae and leaves were most frequently used for the treatment of diseases. This study showed that many people in the studied parts of Kancheepuram district still continue to depend on medicinal plants at least for the treatment of primary healthcare. The traditional healers are dwindling in number and there is a grave danger of traditional knowledge disappearing soon since the younger generation is not interested to carry on this tradition

    Macro micronutrients and Antioxidant Potentials of Plants and Fungal based Food from Tawang Area Arunachal Pradesh India

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    Certain variety of plants such as vegetables, spices and seaweed are abundantly being grown in high altitude cold desert region of Tawang in Arunachal Pradesh, India. Therefore, five different vegetables, spices and seaweed were taken from that particular cold region viz., finger millet, nori seaweed, pepper corn, bean and mushroom have been selected based on the higher consumption of people of Northeast (NE) India for the proximate analysis, mineral, antioxidant and vitamin contents. So far, there is no nutritional composition studies have been carried out with available vegetables, spices and seaweeds growing in NE. For this reason, this study was undertaken to determine the macro and micro nutrients and antioxidant potential of these plant foods. Different analyzed varieties were significantly different for proximate composition and mineral content, and each variety showed significant differences. Common bean showed higher percentage of protein with 35.09% and fat percentage of the finger millet is higher (9.2%) as compared to other varieties from other regions (1-1.5%). Higher crude fibre was assessed in mushroom with 47.77% followed with pepper corn (38.42%), bean with 30.987%, and finger millet (5.14%).Calcium was higher in finger millet with 225 mg per 100g whereas iron content was higher in mushroom with 652 mg followed with beans (543 mg), pepper corn (408 mg per 100g). Higher amount of polyphenols observed in finger millet with 8.716 ”g (GAE)/mg and highest total flavonoids in pepper corn with 48.196 ”g (RU)/ml. Likewise, highest FRAP in finger millet noticed with 72.0 ”g of FeSO4 equivalent /mg and reducing power (ascorbic acid equivalent /mg) in mushroom (244.0) and pepper corn (242.0). All samples had higher metal chelating activity between 86.657- 83.383 IC50 ”g. Similarly, higher amount of vit B6 was noted in pepper corn with 197.0 mg while lowest in seaweed with 1.76 mg/100gm. &nbsp

    Regulation of Erk1/2 activation by osteopontin in PC3 human prostate cancer cells

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    <p>Abstract</p> <p>Background</p> <p>Osteopontin (OPN) has been shown to play many roles in the progression of cancer. We have recently demonstrated the activation of Akt by OPN. Integrin-linked kinase and PI3-kinase are integral proteins in OPN/AKT pathway in PC3 cells. To investigate the role of the extracellular receptors in OPN signaling, we have examined the spatio-temporal regulation of CD44 and integrin αvÎČ3 receptor in OPN-induced Akt activation in PC3 cells.</p> <p>Results</p> <p>Here, our studies demonstrate that OPN can activate Akt either through the α<sub>V</sub>ÎČ<sub>3 </sub>integrin or the CD44 cell surface receptor. Members of the Mitogen Activated Protein Kinase (MAPK) family have been shown to be up-regulated in a variety of human cancers and have been implicated in the metastatic behavior. Our studies have demonstrated an increase in the phosphorylation of c-Raf at Ser259 and Ser338 in PC3 cells over-expressing OPN. This increase matches up with the Erk1/2 phosphorylation at Thr202/204 and activation. However, the inhibition of Akt activity augments the phosphorylation state of ERK1/2 to two to three fold with a concomitant reduction in the phosphorylation state of c-Raf at Ser259.</p> <p>Conclusions</p> <p>Regulation c-Raf phosphorylation at Ser259 has a role in the anti-apoptotic pathways mediated by Akt or Raf/MEK/ERK proteins. OPN may have dual effects in the activation of Erk1/2. We propose this based on the observations that while OPN activates c-Raf and Erk1/2; it also acts to inhibit c-Raf and Erk1/2 activation through Akt pathway. Our observations suggest that the activation of c-Raf-ERK cascade may promote cell cycle arrest in prostate cancer cells and OPN signaling has a role in the anti-apoptotic mechanism.</p

    Stochastic Perishable Inventory System Analysis With Two Types Of Customers In The Supply Chain

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    In the supply chain model being examined in this study, there are two different client expectations. A warehouse, a single distribution centre, a single retailer, and the handling of a single perishable product make up the system. Retailer node (lower echelon) assumes a A(s, S) type inventory system with Poisson demand and exponentially dispersed lead times, and distribution centre assumes a (0, kQ) policy (middle echelon). Demands that happen during the times when there is no stock are taken to be lost sales. The merchandise is sent from the distribution centre to the stores in packs of Q(= S − s) items. It is believed that only the retailer nodes with rate Îł experience item perishability. The upper echelon (warehouse) replaces the distribution center’s stock with exponentially distributed lead times due to its ample supply. Demands arrive at the retailer node in two categories: (i) normal customers; and (ii) priority customers, with arrival rates of α and ÎČ. It is possible to obtain the metrics of system performance as well as the steady state probability distribution of system states. The proposed paradigm is demonstrated with numerical examples

    Polyphosphoinositides-dependent regulation of the osteoclast actin cytoskeleton and bone resorption

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    BACKGROUND: Gelsolin, an actin capping protein of osteoclast podosomes, has a unique function in regulating assembly and disassembly of the podosome actin filament. Previously, we have reported that osteopontin (OPN) binding to integrin α(v)ÎČ(3 )increased the levels of gelsolin-associated polyphosphoinositides, podosome assembly/disassembly, and actin filament formation. The present study was undertaken to identify the possible role of polyphosphoinositides and phosphoinositides binding domains (PBDs) of gelsolin in the osteoclast cytoskeletal structural organization and osteoclast function. RESULTS: Transduction of TAT/full-length gelsolin and PBDs containing gelsolin peptides into osteoclasts demonstrated: 1) F-actin enriched patches; 2) disruption of actin ring; 3) an increase in the association polyphosphoinositides (PPIs) with the transduced peptides containing PBDs. The above-mentioned effects were more pronounced with gelsolin peptide containing 2 tandem repeats of PBDs (PBD (2)). Binding of PPIs to the transduced peptides has resulted in reduced levels of PPIs association with the endogenous gelsolin, and thereby disrupted the actin remodeling processes in terms of podosome organization in the clear zone area and actin ring formation. These peptides also exhibited a dominant negative effect in the formation of WASP-Arp2/3 complex indicating the role of phosphoinositides in WASP activation. The TAT-PBD gelsolin peptides transduced osteoclasts are functionally defective in terms of motility and bone resorption. CONCLUSIONS: Taken together, these data demonstrate that transduction of PBD gelsolin peptides into osteoclasts produced a dominant negative effect on actin assembly, motility, and bone resorption. These findings indicate that phosphoinositide-mediated signaling mechanisms regulate osteoclast cytoskeleton, podosome assembly/disassembly, actin ring formation and bone resorption activity of osteoclasts
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