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A recent study of the meiofauna from several intertidal sites along the coast of Chile yielded several gastrotrich specimens. The number of specimens was too small to assess the ecology of the individual species; however, as there are no published records of Gastrotricha in Chile until recently, it is important to document the presence of this group in order to stimulate further research. We report specimens of the genera Lepidodasys , Cephalodasys , Macrodasys , Tetranchyroderma , Xenotrichula and several morphotypes of Turbanella . Additionally, we provide some initial data on the population density of Lepidodasys sp. at Coihuin (Puerto Montt) and an observation of them feeding on nematodes. Normal 0 21 false false false /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Normale Tabelle"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; mso-bidi-font-size:12.0pt; font-family:"Liberation Serif","serif"; mso-ansi-language:EN-GB; mso-fareast-language:ZH-CN; mso-bidi-language:HI;} Normal 0 21 false false false /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Normale Tabelle"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; mso-bidi-font-size:12.0pt; font-family:"Liberation Serif","serif"; mso-ansi-language:EN-GB; mso-fareast-language:ZH-CN; mso-bidi-language:HI;}

In recent decades, the alteration of coastal food webs (via aquaculture, fishing, and leisure activities), nutrient loading, and an expansion of monitoring programs have prompted an apparent worldwide rise in Harmful Algae Blooms (HABs). Over this time, a parallel increase in HABs has also been observed in the Chilean southern austral region (Patagonia fjords). HAB species like Alexandrium catenella—responsible for Paralytic Shellfish Poisoning (PSP)—are of great public concern due to their negative socioeconomic impacts and significant northward geographical range expansion. Many toxic dinoflagellate species (like A. catenella) produce benthic resting cysts, yet a holistic understanding of the physical-chemical and biological conditions influencing the distributions of cysts in this region is lacking. In this study, we measured a combination of hydrographic (temperature, salinity, and dissolved oxygen) and sediment physical-chemical properties (temperature, pH and redox potential), in addition to meiofaunal abundances –as sediment bioturbators and potential cyst predators– to determine the factors influencing dinoflagellate cyst distribution, with emphasis on A. catenella in and around a “hotspot” area of southern Chile. An analysis of similarities (ANOSIM) test revealed significant differences (p

Background Due to the importance of both prostaglandins (PGs) and leukotrienes (LTs) as pro-inflammatory mediators, and the potential for eicosanoid shunting in the presence of pathway target inhibitors, we have investigated an approach to inhibiting the formation of both PGs and LTs as part of a multi-targeted drug discovery effort. Methods We generated ligand-protein X-ray crystal structures of known inhibitors of microsomal prostaglandin E2 synthase-1 (mPGES-1) and the 5-Lipoxygenase Activating Protein (FLAP), with their respective proteins, to understand the overlapping pharmacophores. We subsequently used molecular modeling and structure-based drug design (SBDD) to identify hybrid structures intended to inhibit both targets. Results This work enabled the preparation of compounds 4 and 5, which showed potent in vitro inhibition of both targets. Significance Our findings enhance the structural understanding of mPGES-1 and FLAP's unique ligand binding pockets and should accelerate the discovery of additional dual inhibitors for these two important integral membrane protein drug targets.

The impact on the meiofaunal assemblage of the bioturbation caused by Chilean Flamingos (Phoenicopterus chilensis) feeding on the tidal flat at Caulin, southern Chile was investigated. The flamingos walk in circles in shallow water, moving their feet up and down in order to suspend the sediment which is then filtered through the lamellae in their beaks in order to capture their prey. Which component of the benthos the flamingos are targeting has yet to be unequivocally determined. Meiofauna are one potential food source as they are extremely abundant at the site and the filtering capacity of the flamingos could potentially retain meiofauna. Two possible hypotheses concerning the impact of flamingo feeding activity on the meiofaunal assemblage were tested: hypothesis 1 that the flamingos are feeding on the meiofaunal assemblage, and hypothesis 2 that the flamingos are displacing the meiofaunal assemblage over short distances. Meiofaunal samples were collected on four occasions (autumn, winter, spri...

The high expression of proviral insertion site of Moloney murine leukemia virus kinases (Pim-1, -2, and -3) in cancers, particularly the hematopoietic malignancies, is believed to play a role in promoting cell survival and proliferation while suppressing apoptosis. The three isoforms of Pim protein appear largely redundant in their oncogenic functions. Thus, a pan-Pim kinase inhibitor is highly desirable. However, cell active pan-Pim inhibitors have proven difficult to develop because Pim-2 has a low Km for ATP and therefore requires a very potent inhibitor to effectively block the kinase activity at cellular ATP concentrations. Herein, we report a series of quinazolinone-pyrrolopyrrolones as potent and selective pan-Pim inhibitors. In particular, compound 17 is orally efficacious in a mouse xenograft model (KMS-12 BM) of multiple myeloma, with 93% tumor growth inhibition at 50 mg/kg QD upon oral dosing.

The Chilean salmon industry has undergone a rapid development making the country the world’s second largest producer of farmed salmon, but this growth has been accompanied by an intensive use of antibiotics. This overuse has become so significant that Chilean salmon aquaculture currently has one of the highest rates of antibiotic consumption per ton of harvested fish in the world. This review has focused on discussing use of antibiotics and current status of scientific knowledge regarding to incidence of antimicrobial resistance and associated genes in the Chilean salmonid farms. Over recent years there has been a consistent increase in the amount of antimicrobials used by Chilean salmonid farms, from 143.2 tons in 2010 to 382.5 tons in 2016. During 2016, Chilean companies utilized approximately 0.53 kg of antibiotics per ton of harvested salmon, 363.4 tons (95%) were used in marine farms, and 19.1 tons (5%) in freshwater farms dedicated to smolt production. Florfenicol and oxytetracycline were by far the most frequently used antibiotics during 2016 (82.5 and 16.8%, respectively), mainly being used to treat Piscirickettsia salmonis, currently considered the main bacterial threat to this industry. However, the increasing development of this industry in Chile, as well as the intensive use of antimicrobials, has not been accompanied by the necessary scientific research needed to understand the impact of the intensive use of antibiotics in this industry. Over the last two decades several studies assessing antimicrobial resistance and the resistome in the freshwater and marine environment impacted by salmon farming have been conducted, but information on the ecological and environmental consequences of antibiotic use in fish farming is still scarce. In addition, studies reporting the antimicrobial susceptibility of bacterial pathogens, mainly P. salmonis, have been developed, but a high number of these studies were aimed at setting their epidemiological cut-off values. In conclusion, further studies are urgently required, mainly focused on understanding the evolution and epidemiology of resistance genes in Chilean salmonid farming, and to investigate the feasibility of a link between these genes among bacteria from salmonid farms and human and fish pathogens.

Microsomal prostaglandin E synthase 1 (mPGES-1) is an α-helical homotrimeric integral membrane inducible enzyme that catalyzes the formation of prostaglandin E2 (PGE2) from prostaglandin H2 (PGH2). Inhibition of mPGES-1 has been proposed as a therapeutic strategy for the treatment of pain, inflammation, and some cancers. Interest in mPGES-1 inhibition can, in part, be attributed to the potential circumvention of cardiovascular risks associated with anti-inflammatory cyclooxygenase 2 inhibitors (coxibs) by targeting the prostaglandin pathway downstream of PGH2 synthesis and avoiding suppression of antithrombotic prostacyclin production. We determined the crystal structure of mPGES-1 bound to four potent inhibitors in order to understand their structure-activity relationships and provide a framework for the rational design of improved molecules. In addition, we developed a light-scattering-based thermal stability assay to identify molecules for crystallographic studies.

The diversity of free-living nematodes in the beaches of two Antarctic islands, King George and Deception islands was investigated. We used morphological and molecular (LSU, and two fragments of SSU sequences) approaches to evaluate 236 nematodes. Specimens were assigned to at least genera using morphology and were assessed for the presence of cryptic speciation. The following genera were identified: Halomonhystera, Litoditis, Enoploides, Chromadorita, Theristus, Oncholaimus, Viscosia, Gammanema, Bathylaimus, Choanolaimus, and Paracanthonchus; along with specimens from the families Anticomidae and Linhomoeidae. Cryptic speciation was identified within the genera Halomonhystera and Litoditis. All of the cryptic species identified live sympatrically. The two cryptic species of Halomonhystera exhibited no significant morphological differences. However, Litoditis species 2 was significantly larger than Litoditis species 1. The utility of molecular data in confirming the identifications of some of the morphologically more challenging families of nematodes was demonstrated. In terms of which molecular sequences to use for the identification of free-living nematodes, the SSU sequences were more variable than the LSU sequences, and thus provided more resolution in the identification of cryptic speciation. Finally, despite the considerable amount of time and effort required to put together genetic and morphological data, the resulting advance in our understanding of diversity and ecology of free-living marine nematodes, makes that effort worthwhile.

The mystacocarid Ctenocheilocaris galvarini is a member of the intertidal meiofauna in exposed sandy beaches along the coast of Chile. Originally described by Dahl (1952) from sub-tidal sediment off Isla Guafo, the only other published record is from semi-fine intertidal sand in Las Cruces. This paper presents a variety of new records of C. galvarini based on both quantitative and qualitative sampling of the coast of Chile between 18°S and 54°S. Ctenocheilocaris galvarini is found primarily in southern Chile, south of 32°, in the intertidal zone of intermediate beaches, in fine sand (Wentworth scale) most likely distributed between the level of the water-table and the surface, but avoiding dry sand.

Free-living nematodes are an important component of the marine benthos. In Chile there have been few studies on this group, and the majority has focused on the morphological aspect only. In this study, ribosomal 18S RNA and mitochondrial COI genes were used as genetic markers to complement morphological analyses to study the continental and Antarctic Chilean marine nematofauna. Different protocols for fixing, extracting and amplifying DNA were also tested. Not all the possible combinations produced good results. In fact, only the 18S gene showed consistently results. Phylogenetic analyses showed some discordance between classical taxonomy (i.e., based on morphology) and molecular data. These results suggest that taxonomic classification using integrative approaches including morphological characteristics and molecular information is needed to study the diversity and evolution of this complex group.

Structure-activity relationship (SAR) investigations of a novel class of triazolopyridazinone p38α mitogen activated protein kinase (MAPK) inhibitors are disclosed. From these studies, increased in vitro potency was observed for 2,6-disubstituted phenyl moieties and N-ethyl triazolopyridazinone cores due to key contacts with Leu108, Ala157 and Val38. Further investigation led to the identification of three compounds, 3g, 3j and 3m that are highly potent inhibitors of LPS-induced MAPKAP kinase 2 (MK2) phosphorylation in 50% human whole blood (hWB), and possess desirable in vivo pharmacokinetic and kinase selectivity profiles.

The latitudinal pattern of species richness of free-living marine nematodes from exposed sandy beaches along the coast of Chile between 18 and 42° S was examined. Unlike many other examinations of latitudinal gradients, this study is not based on data mined from the literature, but on samples collected specifically to examine these themes. Five replicate quantitative 50 cm3 samples of sediment were taken from the zone of retention of 66 exposed sandy beaches. The free-living nematode fauna was identified and quantified to species level. The data were then examine using ordinary least squares and simultaneous autoregressive model (SARerr) regression methods, examining the associations between species richness and latitude, coastline complexity, and sea surface temperature, primary productivity of the adjacent coastal waters and mean latitudinal range size. The species richness of free-living marine nematodes from exposed sandy beaches along the coast of Chile decreased with increasing latitude and was strongly associated with mean annual sea surface temperature. Mean latitudinal range size increased with increasing latitude, supporting Rapoport’s rule, and decreased with increasing species richness. The results suggest that the nematode fauna of exposed sandy beaches is derived from a low latitude fauna that has dispersed to higher latitudes, but that many species may be physiologically constrained, by temperature, from dispersing further south.

Extensive beds of the mussel Perumytilus purpuratus are a common feature of the mid-intertidal along the Chilean coast. The beds are an alternative stable state that results from the anthropogenic removal of the keystone predator Concholepas concholepas. The mussel beds constitute an important microhabitat that supports a large number of small mobile macrofaunal and meiofaunal species. This paper seeks to determine if the absence of extensive mussel beds within a Marine Reserve results in a reduced species richness. We used ‘live’ artificial mussel beds on plates to determine the species richness of fauna both inside and outside the Marine Reserve. There were no significant differences in the species richness (Smean) on plates inside and outside the Marine Reserve but there were differences with the natural mussel beds. Though the assemblages on the plates did not reach maturity ‘live’, artificial mussel beds could prove a useful tool for assessing the species richness of small mobile macrofauna and meiofauna.

Through the analysis of X-ray crystallographic information and previous SAR studies, a novel series of protein kinase B (PKB/AKT) inhibitors was developed. The compounds showed nanomolar inhibition of AKT1 and were selective against cyclin-dependent kinase 2 (CDK2).

The p38α mitogen-activated protein (MAP) kinase is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1β and tumor necrosis factor α. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, and Crohn’s disease, as well as other diseases where aberrant cytokine signaling is the driver of disease. In this communication, we describe a novel class of 7-alkyl-1,5-bis-aryl-pyrazolopyridinone-based p38α inhibitors. In particular, compound 3f is highly potent in the enzyme and cell-based assays, selective in an Ambit kinase screen, and efficacious (ED50 ≤ 0.01 mg/kg) in the rat collagen induced arthritis (CIA) model.

A series of 2-aminothiadiazole of inhibitors of AKT1 is described. SAR relationships are discussed, along with selectivity for protein kinase A (PKA) and cyclin-dependent kinase 2 (CDK2). Moderate selectivity observed in several compounds for AKT1 versus PKA is rationalized by X-ray crystallographic analysis. Key compounds showed activity in cellular assays measuring phosphorylation of two AKT substrates, PRAS40 and FKHRL1. Compound 30 was advanced to a mouse liver PD assay, where it showed dose-dependent inhibition of AKT activity, as measured by the inhibition of phospho-PRAS40.

A 2-aminothiazole derivative 1 was developed as a potential inhibitor of the oncology target AKT, a serine/threonine kinase. When incubated in rat and human liver microsomes in the presence of NADPH, 1 underwent significant metabolic activation on its 2-aminothiazole ring, leading to substantial covalent protein binding. Upon addition of glutathione, covalent binding was reduced significantly, and multiple glutathione adducts were detected. Novel metabolites from the in vitro incubates were characterized by LC-MS and NMR to discern the mechanism of bioactivation. An in silico model was developed based on the proposed mechanism and was employed to predict bioactivation in 23 structural analogues. The predictions were confirmed empirically for the bioactivation liability, in vitro, by LC-MS methods screening for glutathione incorporation. New compounds were identified with a low propensity for bioactivation.

The p38 mitogen-activated protein kinase (MAPK) is a central signaling molecule in many proinflammatory pathways, regulating the cellular response to a multitude of external stimuli including heat, ultraviolet radiation, osmotic shock, and a variety of cytokines especially interleukin-1beta and tumor necrosis factor alpha. Thus, inhibitors of this enzyme are postulated to have significant therapeutic potential for the treatment of rheumatoid arthritis, inflammatory bowel disease, osteoporosis, and many other diseases where aberrant cytokine signaling is the driver of disease. Herein, we describe a novel class of 3-amino-7-phthalazinylbenzoisoxazole-based inhibitors. With relatively low molecular weight, these compounds are highly potent in enzyme and cell-based assays, with minimal protein shift in 50% human whole blood. Compound 3c was efficacious (ED 50 = 0.05 mg/kg) in the rat collagen induced arthritis (CIA) model.

c-Met is a receptor tyrosine kinase that plays a key role in several cellular processes but has also been found to be overexpressed and mutated in different human cancers. Consequently, targeting this enzyme has become an area of intense research in drug discovery. Our studies began with the design and synthesis of novel pyrimidone 7, which was found to be a potent c-Met inhibitor. Subsequent SAR studies identified 22 as a more potent analog, whereas an X-ray crystal structure of 7 bound to c-Met revealed an unexpected binding conformation. This latter finding led to the development of a new series that featured compounds that were more potent both in vitro and in vivo than 22 and also exhibited different binding conformations to c-Met. Novel c-Met inhibitors have been designed, developed, and found to be potent in vitro and in vivo.

Deregulation of the receptor tyrosine kinase c-Met has been implicated in human cancers. Pyrazolones with N-1 bearing a pendent hydroxyalkyl side chain showed selective inhibition of c-Met over VEGFR2. However, studies revealed the generation of active, nonselective metabolites. Blocking this metabolic hot spot led to the discovery of 17 (AMG 458). When dosed orally, 17 significantly inhibited tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models with no adverse effect on body weight.

Background: Members of the protein kinase C (PKC) family are key signalling mediators in immune responses, and pharmacological inhibition of PKCs may be useful for treating immune-mediated diseases. Objective: To review and discuss the insights gained so far into various PKC isozymes and the therapeutic potential and challenges of developing PKC inhibitors for immune disorder therapy. Methods: A literature review of the role of PKCs in immune cell signalling and recent studies describing immune functions associated with PKC isozyme deficiency in relevant mouse disease models, followed by specific case studies of current and potential therapeutic strategies targeting PKCs. Results/conclusion: There is vast amount of data supporting PKC isozymes as attractive drug targets for certain immune disorders. Although the development of specific PKC isozyme inhibitors has been challenging, some progress has been made. It remains to be seen if broad-scale or isozyme-selective inhibition of PKC will have clinical eff...

The combined effect of ocean acidification and warming is expected to have significant effects on several traits of marine organisms. The gastropod Concholepas concholepas is a rocky shore keystone predator characteristic of the south-eastern Pacific coast of South America and an important natural resource exploited by small-scale artisanal fishermen along the coast of Chile and Peru. In this study, we used small juveniles of C. concholepas collected from the rocky intertidal habitats of southern Chile (39 °S) to evaluate under laboratory conditions the potential consequences of projected near-future levels of ocean acidification and warming for important early ontogenetic traits. The individuals were exposed long-term (5.8 months) to contrasting pCO2 (ca. 500 and 1400 μatm) and temperature (15 and 19 °C) levels. After this period we compared body growth traits, dislodgement resistance, predator-escape response, self-righting and metabolic rates. With respect to these traits there was no evidence of a synergistic interaction between pCO2 and temperature. Shell growth was negatively affected by high pCO2 levels only at 15 °C. High pCO2 levels also had a negative effect on the predator-escape response. Conversely, dislodgement resistance and self-righting were positively affected by high pCO2 levels at both temperatures. High tenacity and fast self-righting would reduce predation risk in nature and might compensate for the negative effects of high pCO2 levels on other important defensive traits such as shell size and escape behaviour. We conclude that climate change might produce in C. concholepas positive and negative effects in physiology and behaviour. In fact, some of the behavioural responses might be a consequence of physiological effects, such as changes in chemosensory capacity (e.g. predator-escape response) or secretion of adhesive mucous (e.g. dislodgement resistance). Moreover, we conclude that positive behavioural responses may assist in the adaptation to negative physiological impacts, and that this may also be the case for other benthic organisms.

The hypothesis investigated in this paper is that the interstitial polychaete Saccocirrus sonomacus is excluded from beaches impacted by tailing disposal as a result of the blocking of the interstitial space and not by a response to the toxicity of elevated copper concentrations. Field evidence suggested that abundances of S. sonomacus on beaches where they would be expected to occur under natural conditions are lower when a beach has received a significant amount of tailings. In choice experiments, S. sonomacus always preferred an open coarse sand matrix to one where the interstitial spaces had been blocked by fine sand (a tailings substitute). Using invitro bioassays, we found that the LC50 for S. sonomacus with copper was 44 μg Cu l−1, this being higher than the values of interstitial labile copper measured on the beaches investigated in this study. We therefore accept the hypothesis of a physically mediated exclusion rather than a toxically mediated one.

We investigated the stability of three different ensembles of the 36-mer villin headpiece subdomain, the native, a compact folding intermediate, and the random coil. Structures were taken from a 1-micros molecular dynamics folding simulation and a 100-ns control simulation on the native structure. Our approach for each conformation is to first determine the solute internal energy from the molecular mechanics potential and then to add the change resulting from solvation (DeltaG(solv)). Explicit water was used to run the simulation, and a continuum model was used to estimate DeltaG(solv) with the finite difference Poisson-Boltzmann model accounting for the polarization part and a linearly surface area-dependent term for the non-polar part. We leave out the solute vibrational entropy from these values but demonstrate that there is no statistical difference among the native, folding intermediate, and random coil ensembles. We find the native ensemble to be approximately 26 kcal/mol more stable than the folding intermediate and approximately 39 kcal/mol more stable than the random coil ensemble. With an experimental estimate for the free energy of denaturation equal to 3 kcal/mol, we approximate the non-native degeneracy to lie between 10(16) and 10.(25) We also present a possible scheme for the mechanism of folding, first-order exponential decay of a putative transition state, with an estimate for the t(1/2) of folding of approximately 1 micros.

Deregulation of c-Met receptor tyrosine kinase activity leads to tumorigenesis and metastasis in animal models. More importantly, the identification of activating mutations in c-Met, as well as MET gene amplification in human cancers, points to c-Met as an important target for cancer therapy. We have previously described two classes of c-Met kinase inhibitors (class I and class II) that differ in their binding modes and selectivity profiles. The class II inhibitors tend to have activities on multiple kinases. Knowledge of the binding mode of these molecules in the c-Met protein led to the design and evaluation of several new class II c-Met inhibitors that utilize various 5-membered cyclic carboxamides to conformationally restrain key pharmacophoric groups within the molecule. These investigations resulted in the identification of a potent and novel class of pyrazolone c-Met inhibitors with good in vivo activity.

A novel class of pyrazolopyridazine p38α mitogen-activated protein kinase (MAPK) inhibitors is disclosed. A structure activity relationship (SAR) investigation was conducted driven by the ability of these compounds to inhibit the p38α enzyme, the secretion of TNFα in a LPS-challenged THP1 cell line and TNFα-induced production of IL-8 in the presence of 50% human whole blood (hWB). This study resulted in the discovery of several inhibitors with IC50 values in the single-digit nanomolar range in hWB. Further investigation of the pharmacokinetic profiles of these lead compounds led to the identification of three potent and orally bioavailable p38α inhibitors 2h, 2m, and 13h. Inhibitor 2m was found to be highly selective for p38α/β over a panel of 402 other kinases in Ambit screening, and was highly efficacious in vivo in the inhibition of TNFα production in LPS-stimulated Lewis rats with an ED50 of ca. 0.08 mg/kg.

Investigations into the structure-activity relationships (SAR) of a series of phthalazine-based inhibitors of p38 are described. These efforts originated from quinazoline 1 and through rational design led to the development of a series of orally bioavailable, potent, and selective inhibitors. Kinase selectivity was achieved by exploiting a collection of interactions with p38alpha including close contact to Ala157, occupation of the hydrophobic gatekeeper pocket, and a residue flip with Gly110. Substitutions on the phthalazine influenced the pharmacokinetic properties, of which compound 16 displayed the most desirable profile. Oral dosing (0.03 mg/kg) of 16 in rats 1 h prior to LPS challenge gave a >50% decrease in TNFalpha production.

17 páginas, 5 tablas., [EN] A comprehensive literature review was conducted to determine the species richness of all the possible taxa of free-living benthic marine invertebrates in Chile. In addition, the extent of endemism to the Pacific Islands and deep-sea, the number of non-indigenous species, and the contribution that the Chilean benthic marine invertebrate fauna makes to the world benthic marine invertebrate fauna was examined. A total of 4,553 species were found. The most speciose taxa were the Crustacea, Mollusca and Polychaeta. Species richness data was not available for a number of taxa, despite evidence that these taxa are present in the Chilean benthos. The Chilean marine invertebrate benthic fauna constitutes 2.47 % of the world marine invertebrate benthic fauna. There are 599 species endemic to the Pacific Islands and 205 in the deep-sea. There are 25 invasive or non-indigenous species so far identified in Chile. Though the Chilean fauna is speciose there is still a considerable amount of diversity yet to be described, particularly amongst the small bodied invertebrates and from the less well explored habitats, such as the deep-sea., [ES] Se realizó una revisión exhaustiva de la literatura para determinar la riqueza de especies de todos los taxa de invertebrados bentónicos de vida libre en Chile. Además, se analizó el endemismo de invertebrados marinos bentónicos para las islas chilenas del Pacífico y el mar profundo y el número de especies no indígenas; del mismo modo que la contribución de estos invertebrados a la riqueza mundial de invertebrados bentónicos marinos. Para Chile se acumuló un total de 4.553 especies de invertebrados bentónicos. Los taxa con más especies fueron Crustacea, Mollusca y Polychaeta. En algunos taxa de invertebrados no se encontró información sobre la diversidad de especies presentes en Chile, a pesar de existir evidencia de que éstos están presentes en el bentos marino chileno. Los invertebrados bentónicos marinos chilenos contribuyen con el 2,47 % de la riqueza mundial de dichos invertebrados. Se encontraron 599 especies endémicas de las islas chilenas del Pacífico y 205 especies endémicas para el mar profundo. Hasta ahora en Chile se han identificado sólo 25 especies invasoras de invertebrados bentónicos marinos. Los invertebrados bentónicos marinos chilenos son diversos, pero aún hay especies no descritas, especialmente dentro de los invertebrados bentónicos de pequeño tamaño corporal que se encuentran en hábitat poco explorados, como por ejemplo el mar profundo., We acknowledge FONDAP-FONDECYT grant 1501-0001, Program 6 supporting M.R. Lee post-doctoral training. The Mellon Foundation Grant to J. C. Castilla. and S. Navarrete provided funds for the work of C. Hermosilla. We are grateful to M. Pardo, M. Rivadeneira and N. Ruiz-Tagle for their help compiling the database. We also acknowledge financial support from the FONDAP-FONDECYT grant 1501-0001 to the Center for Advanced Studies in Ecology & Biodiversity (JCC & MF) and a Pew Marine Conservation Fellowship to MF.

Mitogen-activated protein kinase p38 is a serine/threonine kinase originally isolated from lipopolysaccharide (LPS) stimulated monocytes. There are four isoforms p38α, p38β, p38γ, and p38δ. The most thoroughly studied isoform is p38α, whose activation has been observed in many hematopoietic and nonhematopoietic cell types upon appropriate stimuli. Subsequently, p38α kinase has been shown to be involved in the biosynthesis of TNFα and IL-1β at the translational and transcriptional level. MAP kinase p38agr; represents a point of convergence for multiple signaling processes that are activated in inflammation and thus a key potential target for the modulation of cytokine production. The discovery and publication of p38α and the pyridinyl-imidazole inhibitor initiated a huge effort by many companies to develop p38α inhibitors as potential treatment for inflammatory diseases. Herein we provide a brief overview of recent reported clinical results for AMG 548, BIRB 796, VX 702, SCIO 469, and SCIO 323. However, our focus will be on the binding modes of these inhibitors and other p38 inhibitors in the recent literature.

A sediment quality triad (SQT) assessment was made of the impact of copper mine tailings disposal on littoral meiofaunal assemblages in the Atacama region of northern Chile. This situation is unusual in that the disposal is direct into the high-energy coastal system and not via a river estuary or other low-energy environment. This situation also allows for the examination of the impact of copper mine tailings in the absence of confounding effects from other pollutants. The three components of the SQT were: 1. an analysis of the bioavailable metals in both the sedimentary porewater and the adjacent seawater, 2. a microcosm bioassay of both sediments and seawaters using meiofaunal assemblages, and 3. quantitative field samples of the meiofaunal assemblages. Twelve study sites with varying degrees of impact were used, including three reference sites. The study identified that both the meiofaunal assemblage densities and taxa diversities decrease with increasing levels of bioavailable copper, that the Foraminifera and Harpacticoida are sensitive to copper, and that otoplanid Turbellaria are often characteristic of impacted sites; tailings also have both chemical and physical impacts on the environment. In some cases the physical impact of tailings is more important in excluding some organisms e.g. the interstitial polychaete, Saccocirrus sonomacus, from a site than is their chemical impact.

We discuss the use of the nematode to copepod ratio in relation to determining the extent of metals impact using the Chanaral area of northern Chile, where the dumping of copper mine tailings has taken place for many years, as an example. Data were collected from 12 beaches in the area on eight occasions between January 1997 and October 1998. We find that the ratio is not a good predictor of pollution due to the generally low densities of meiofauna on impacted beaches and the absence of harpacticoid copepods from those beaches. We suggest that in the case of metal pollution the mean number of Harpacticoida per site may be a better indicator of impact stress. We rule out the use of the nematode to copepod ratio as an indicator in biomonitoring studies where metal enrichment is thought to occur.