Inhibition of p300 lysine acetyltransferase activity by luteolin reduces tumor growth in head and neck squamous cell carcinoma (HNSCC) xenograft mouse model

Chromatin acetylation is attributed with distinct functional relevance with respect to gene expression in normal and diseased conditions thereby leading to a topical interest in the concept of epigenetic modulators and therapy. We report here the identification and characterization of the acetylation inhibitory potential of an important dietary flavonoid, luteolin. Luteolin was found to inhibit p300 acetyltransferase with competitive binding to the acetyl CoA binding site. Luteolin treatment in a xenografted tumor model of head and neck squamous cell carcinoma (HNSCC), led to a dramatic reduction in tumor growth within 4 weeks corresponding to a decrease in histone acetylation. Cells treated with luteolin exhibit cell cycle arrest and decreased cell migration. Luteolin treatment led to an alteration in gene expression and miRNA profile including up-regulation of p53 induced miR-195/215, let7C; potentially translating into a tumor suppressor function. It also led to down regulation of oncomiRNAs such as miR-135a, thereby reflecting global changes in the microRNA network. Furthermore, a direct correlation between the inhibition of histone acetylation and gene expression was established using chromatin immunoprecipitation on promoters of differentially expressed genes. A network of dysregulated genes and miRNAs was mapped along with the gene ontology categories, and the effects of luteolin were observed to be potentially at multiple levels: at the level of gene expression, miRNA expression and miRNA processing.

Autoregulation of topoisomerase I expression by supercoiling sensitive transcription

The opposing catalytic activities of topoisomerase I (TopoI/relaxase) and DNA gyrase (supercoiling enzyme) ensure homeostatic maintenance of bacterial chromosome supercoiling. Earlier studies in Es-cherichia coli suggested that the alteration in DNA supercoiling affects the DNA gyrase and TopoI expression. Although, the role of DNA elements around the promoters were proposed in regulation of gyrase, the molecular mechanism of supercoiling mediated control of TopoI expression is not yet understood. Here, we describe the regulation of TopoI expression from Mycobacterium tuberculosis and Mycobac-terium smegmatis by a mechanism termed Supercoiling Sensitive Transcription (SST). In both the organisms, topoI promoter(s) exhibited reduced activity in response to chromosome relaxation suggesting that SST is intrinsic to topoI promoter(s). We elucidate the role of promoter architecture and high transcriptional activity of upstream genes in topoI regulation. Analysis of the promoter(s) revealed the presence of suboptimal spacing between the -35 and -10 elements, rendering them supercoiling sensitive. Accordingly, upon chromosome relaxation, RNA polymerase occupancy was decreased on the topoI promoter region implicating the role of DNA topology in SST of topoI. We propose that negative supercoiling induced DNA twisting/writhing align the -35 and -10 elements to facilitate the optimal transcription of topoI.

Structure-flexoelastic properties of bimesogenic liquid crystals

In this paper, we report on the flexoelastic and viscoelastic ratios for a number of bimesogens compounds with the same generic structure. Values are obtained indirectly by measuring the flexoelectro-optic response in the chiral nematic phase. By varying the molecular structure we alter the bend angle, transverse dipole moment, and length of the molecule. First, to examine the influence of the bend angle we use a homologous series whereby the only alteration in the molecular structure is the number of methylene units in the aliphatic spacer, n. Results show that the flexoelastic ratio, e K, and the effective flexoelectric coefficient, e, both exhibit an odd-even effect with values for n=odd being greater than that for n=even. This is understood in terms of an increase in the bend angle of the molecule and an increase in the transverse dipole moment. Second, in order to investigate the impact of the dipole moment, we have altered the mesogenic units so as to vary the longitudinal dipole moment and used different linkages in the aliphatic spacer in an attempt to alter the transverse dipole moment. Qualitatively, the results demonstrate that the odd-spaced bimesogen with larger transverse dipole moments exhibit larger flexoelastic ratios. © 2007 The American Physical Society.

Evaluation of bioactive sphingolipids in 4-HPR-resistant leukemia cells

Background -- N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide) is a synthetic retinoid with potent pro-apoptotic activity against several types of cancer, but little is known regarding mechanisms leading to chemoresistance. Ceramide and, more recently, other sphingolipid species (e.g., dihydroceramide and dihydrosphingosine) have been implicated in 4-HPR-mediated tumor cell death. Because sphingolipid metabolism has been reported to be altered in drug-resistant tumor cells, we studied the implication of sphingolipids in acquired resistance to 4-HPR based on an acute lymphoblastic leukemia model. Methods -- CCRF-CEM cell lines resistant to 4-HPR were obtained by gradual selection. Endogenous sphingolipid profiles and in situ enzymatic activities were determined by LC/MS, and resistance to 4-HPR or to alternative treatments was measured using the XTT viability assay and annexin V-FITC/propidium iodide labeling. Results -- No major crossresistance was observed against other antitumoral compounds (i.e. paclitaxel, cisplatin, doxorubicin hydrochloride) or agents (i.e. ultra violet C, hydrogen peroxide) also described as sphingolipid modulators. CCRF-CEM cell lines resistant to 4-HPR exhibited a distinctive endogenous sphingolipid profile that correlated with inhibition of dihydroceramide desaturase. Cells maintained acquired resistance to 4-HPR after the removal of 4-HPR though the sphingolipid profile returned to control levels. On the other hand, combined treatment with sphingosine kinase inhibitors (unnatural (dihydro)sphingosines ((dh)Sph)) and glucosylceramide synthase inhibitor (PPMP) in the presence or absence of 4-HPR increased cellular (dh)Sph (but not ceramide) levels and were highly toxic for both parental and resistant cells. Conclusions -- In the leukemia model, acquired resistance to 4-HPR is selective and persists in the absence of sphingolipid profile alteration. Therapeutically, the data demonstrate that alternative sphingolipid-modulating antitumoral strategies are suitable for both 4-HPR-resistant and sensitive leukemia cells. Thus, whereas sphingolipids may not be critical for maintaining resistance to 4-HPR, manipulation of cytotoxic sphingolipids should be considered a viable approach for overcoming resistance.

Invasion of Egeria into the Hawkesbury-Nepean River, Australia

The Hawkesbury-Nepean River in New South Wales (NSW), Australia, is the largest river system in the Sydney metropolitan area, and it drains most of the developing areas to the west. This catchment is under increasing pressure from urban expansion and the river frequently experiences extended periods of low flows due to a combination of extensive river regulation and the Australian temperate climate. Added to this, the river and several of its tributaries receive treated sewage and stormwater from various sources. Habitats and biota within the Hawkesbury-Nepean River catchment have been altered since European settlement and many introduced species have spread throughout the terrestrial and aquatic environment (Recher et al. 1993). Submersed macrophyte assemblages within the river have undergone significant changes in their distribution and abundance due to eutrophication, habitat alteration and changes to river flows (Recher et al 1993). Anecdotal evidence and some early unpublished studies suggest that egeria (Egeria densa Planchon), introduced from South America as an aquarium plant, was present in the Hawkesbury-Nepean River prior to 1980. Sainty (1973) reported a persistent and troublesome infestation over a number of years at Wallacia in the upper Nepean River. Here, as part of a larger study on the ecology of macrophyte and invertebrate assemblages associated with anthropogenic disturbance in the Hawkesbury-Nepean River, we document the rapid spread of egeria since 1994. Significant increases in egeria biomass were also found, and we present preliminary evidence which suggest that the native ribbonweed, vallisneria (Vallisneria americana Michx.) is being displaced.

A review of the ecological effectiveness of subtidal marine reserves in Central California, Part I: Synopsis of scientific investigations

Marine reserves, often referred to as no-take MPAs, are defined as areas within which human activities that can result in the removal or alteration of biotic and abiotic components of an ecosystem are prohibited or greatly restricted (NRC 2001). Activities typically curtailed within a marine reserve are extraction of organisms (e.g., commercial and recreational fishing, kelp harvesting, commercial collecting), mariculture, and those activities that can alter oceanographic or geologic attributes of the habitat (e.g., mining, shore-based industrial-related intake and discharges of seawater and effluent). Usually, marine reserves are established to conserve biodiversity or enhance nearby fishery resources. Thus, goals and objectives of marine reserves can be inferred, even if they are not specifically articulated at the time of reserve formation. In this report, we review information about the effectiveness of the three marine reserves in the Monterey Bay National Marine Sanctuary (Hopkins Marine Life Refuge, Point Lobos Ecological Reserve, Big Creek Ecological Reserve), and the one in the Channel Islands National Marine Sanctuary (the natural area on the north side of East Anacapa Island). Our efforts to objectively evaluate reserves in Central California relative to reserve theory were greatly hampered for four primary reasons; (1) few of the existing marine reserves were created with clearly articulated goals or objectives, (2) relatively few studies of the ecological consequences of existing reserves have been conducted, (3) no studies to date encompass the spatial and temporal scope needed to identify ecosystem-wide effects of reserve protection, and (4) there are almost no studies that describe the social and economic consequences of existing reserves. To overcome these obstacles, we used several methods to evaluate the effectiveness of subtidal marine reserves in Central California. We first conducted a literature review to find out what research has been conducted in all marine reserves in Central California (Appendix 1). We then reviewed the scientific literature that relates to marine reserve theory to help define criteria to use as benchmarks for evaluation. A recent National Research Council (2001) report summarized expected reserve benefits and provided the criteria we used for evaluation of effectiveness. The next step was to identify the research projects in this region that collected information in a way that enabled us to evaluate reserve theory relative to marine reserves in Central California. Chapters 1-4 in this report provide summaries of those research projects. Contained within these chapters are evaluations of reserve effectiveness for meeting specific objectives. As few studies exist that pertain to reserve theory in Central California, we reviewed studies of marine reserves in other temperate and tropical ecosystems to determine if there were lessons to be learned from other parts of the world (Chapter 5). We also included a discussion of social and economic considerations germane to the public policy decision-making processes associated with marine reserves (Chapter 6). After reviewing all of these resources, we provided a summary of the ecological benefits that could be expected from existing reserves in Central California. The summary is presented in Part II of this report. (PDF contains 133 pages.)

Radiotherapy plus nimotuzumab or placebo in the treatment of high grade glioma patients: results from a randomized, double blind trial

Background The prognosis of patients bearing high grade glioma remains dismal. Epidermal Growth Factor Receptor (EGFR) is well validated as a primary contributor of glioma initiation and progression. Nimotuzumab is a humanized monoclonal antibody that recognizes the EGFR extracellular domain and reaches Central Nervous System tumors, in nonclinical and clinical setting. While it has similar activity when compared to other anti-EGFR antibodies, it does not induce skin toxicity or hypomagnesemia. Methods A randomized, double blind, multicentric clinical trial was conducted in high grade glioma patients (41 anaplastic astrocytoma and 29 glioblastoma multiforme) that received radiotherapy plus nimotuzumab or placebo. Treatment and placebo groups were well-balanced for the most important prognostic variables. Patients received 6 weekly doses of 200 mg nimotuzumab or placebo together with irradiation as induction therapy. Maintenance treatment was given for 1 year with subsequent doses administered every 3 weeks. The objectives of this study were to assess the comparative overall survival, progression free survival, response rate, immunogenicity and safety. Results The median cumulative dose was 3200 mg of nimotuzumab given over a median number of 16 doses. The combination of nimotuzumab and RT was well-tolerated. The most prevalent related adverse reactions included nausea, fever, tremors, anorexia and hepatic test alteration. No anti-idiotypic response was detected, confirming the antibody low immunogenicity. The mean and median survival time for subjects treated with nimotuzumab was 31.06 and 17.76 vs. 21.07 and 12.63 months for the control group. Conclusions In this randomized trial, nimotuzumab showed an excellent safety profile and significant survival benefit in combination with irradiation.

Respuesta a la sequía de Pinus radiata D. Don y su implicación en los procesos de tolerancia

160 p. (Bibliogr. 141-160)

Novel mechanisms for regulation of cell survival and migration by ceramide 1-phosphate

201 p. : gráf.

Role of G protein coupled inwardly rectifier K+ channels (GIRK) on the neurobiology depression

353 págs.

乳化和润湿反转现象的耗散粒子动力学研究

利用耗散粒子动力学方法,研究了化学驱过程中乳化和润湿反转两个重要的物理化学现象.通过合理划分流体粒子和定义粒子之间相互作用参数,模拟了十二烷基苯磺酸钠、正十二烷和水三组分体系的自发乳化现象;通过附加固壁条件,模拟了在水动力作用下吸附在岩石表面的油珠发生破裂的非自发乳化过程,以及由于表面活性剂在岩石表面吸附而引起的润湿反转现象,比较了润湿反转前后残余油珠的运动情况.模拟结果表明:作为介观力学的离散粒子动力学方法,耗散粒子动力学方法可作为研究包含物理化学现象的化学驱渗流问题的重要手段.

Dissipative particle dynamics simulation of wettability alternation phenomena in the chemical flooding process

Wettability alternation phenomena is considered one of the most important enhanced oil recovery (EOR) mechanisms in the chemical flooding process and induced by the adsorption of surfactant on the rock surface. These phenomena are studied by a mesoscopic method named as dissipative particle dynamics (DPD). Both the alteration phenomena of water-wet to oil-wet and that of oil-wet to water-wet are simulated based on reasonable definition of interaction parameters between beads. The wetting hysteresis phenomenon and the process of oil-drops detachment from rock surfaces with different wettability are simulated by adding long-range external forces on the fluid particles. The simulation results show that, the oil drop is liable to spread on the oil-wetting surface and move in the form of liquid film flow, whereas it is likely to move as a whole on the water-wetting surface. There are the same phenomena occuring in wettability-alternated cases. The results also show that DPD method provides a feasible approach to the problems of seepage flow with physicochemical phenomena and can be used to study the mechanism of EOR of chemical flooding.

Sea-level rise in Hawaii: Implications for future shoreline locations and Hawaii coastal management

Management of coastal development in Hawaii is based on the location of the certified shoreline, which is representative of the upper limit of marine inundation within the last several years. Though the certified shoreline location is significantly more variable than long-term erosion indicators, its migration will still follow the coastline's general trend. The long-term migration of Hawaii’s coasts will be significantly controlled by rising sea level. However, land use decisions adjacent to the shoreline and the shape and nature of the nearshore environment are also important controls to coastal migration. Though each of the islands has experienced local sea-level rise over the course of the last century, there are still locations across the islands of Kauai, Oahu, and Maui, which show long- term accretion or anomalously high erosion rates relative to their regions. As a result, engineering rules of thumb such as the Brunn rule do not always predict coastal migration and beach profile equilibrium in Hawaii. With coastlines facing all points of the compass rose, anthropogenic alteration of the coasts, complex coastal environments such as coral reefs, and the limited capacity to predict coastal change, Hawaii will require a more robust suite of proactive coastal management policies to weather future changes to its coastline. Continuing to use the current certified shoreline, adopting more stringent coastal setback rules similar to Kauai County, adding realistic sea-level rise components for all types of coastal planning, and developing regional beach management plans are some of the recommended adaptation strategies for Hawaii. (PDF contains 4 pages)

Semantic change

[ES] En este trabajo se define el cambio semántico, se analizan las causas de que se produzca y se especifican sus tipos en el griego antiguo.

Improving the chances for developing coastal country success in adapting to climate change

There is an unequivocal scientific consensus that increases in greenhouse gases in the atmosphere drive warming temperatures of air and sea, and acidification of the world’s oceans from carbon dioxide absorbed by the oceans. These changes in turn can induce shifts in precipitation patterns, sea level rise, and more frequent and severe extreme weather events (e.g. storms and sea surge). All of these impacts are already being witnessed in the world’s coastal regions and are projected to intensify in years to come. Taken together, these impacts are likely to result in significant alteration of natural habitats and coastal ecosystems, and increased coastal hazards in low-lying areas. They can affect fishers, coastal communities and resource users, recreation and tourism, and coastal infrastructure. Approaches to planned adaptation to these impacts can be drawn from the lessons and good practices from global experience in Integrated Coastal Management (ICM). The recently published USAID Guidebook on Adapting to Coastal Climate Change (USAID 2009) is directed at practitioners, development planners, and coastal management professionals in developing countries. It offers approaches for assessing vulnerability to climate change and climate variability in communities and outlines how to develop and implement adaptation measures at the local and national levels. Six best practices for coastal adaptation are featured in the USAID Guidebook on Adapting to Coastal Climate Change and summarized in the following sections. (PDF contains 3 pages)