894 resultados para consistent and asymptotically normal estimators


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The purpose of this study is to examine the stages of program realization of the interventions that the Bronx Health REACH program initiated at various levels to improve nutrition as a means for reducing racial and ethnic disparities in diabetes. This study was based on secondary analyses of qualitative data collected through the Bronx Health REACH Nutrition Project, a project conducted under the auspices of the Institute on Urban Family Health, with support from the Centers for Disease Control and Prevention (CDC). Local human subjects' review and approval through the Institute on Urban Family Health was required and obtained in order to conduct the Bronx Health REACH Nutrition Project. ^ The study drew from two theoretical models—Glanz and colleagues' nutrition environments model and Shediac-Rizkallah and Bone's sustainability model. The specific study objectives were two-fold: (1) to categorize each nutrition activity to a specific dimension (i.e. consumer, organizational or community nutrition environment); and (2) to evaluate the stage at which the program has been realized (i.e. development, implementation or sustainability). ^ A case study approach was applied and a constant comparative method was used to analyze the data. Triangulation of data based was also conducted. Qualitative data from this study revealed the following principal findings: (1) communities of color are disproportionately experiencing numerous individual and environmental factors contributing to the disparities in diabetes; (2) multi-level strategies that targeted the individual, organizational and community nutrition environments can appropriately address these contributing factors; (3) the nutrition strategies greatly varied in their ability to appropriately meet criteria for the three program stages; and (4) those nutrition strategies most likely to succeed (a) conveyed consistent and culturally relevant messages, (b) had continued involvement from program staff and partners, (c) were able to adapt over time or setting, (d) had a program champion and a training component, (e) were integrated into partnering organizations, and (f) were perceived to be successful by program staff and partners in their efforts to create individual, organizational and community/policy change. As a result of the criteria-based assessment and qualitative findings, an ecological framework elaborating on Glanz and colleagues model was developed. The qualitative findings and the resulting ecological framework developed from this study will help public health professionals and community leaders to develop and implement sustainable multi-level nutrition strategies for addressing racial and ethnic disparities in diabetes. ^

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The mammalian Forkhead Box (Fox) transcription factor (FoxM1) is implicated in tumorgenesis. However, the role and regulation of FoxM1 in gastric cancer remain unknown.^ I examined FoxM1 expression in 86 cases of primary gastric cancer and 57 normal gastric tissue specimens. I found weak expression of FoxM1 protein in normal gastric mucosa, whereas I observed strong staining for FoxM1 in tumor-cell nuclei in various gastric tumors and lymph node metastases. The aberrant FoxM1 expression is associated with VEGF expression and increased angiogenesis in human gastric cancer. A Cox proportional hazards model revealed that FoxM1 expression was an independent prognostic factor in multivariate analysis. Furthermore, overexpression of FoxM1 by gene transfer significantly promoted the growth and metastasis of gastric cancer cells in orthotopic mouse models, whereas knockdown of FoxM1 expression by small interfering RNA did the opposite. Next, I observed that alteration of tumor growth and metastasis by elevated FoxM1 expression was directly correlated with alteration of VEGF expression and angiogenesis. In addition, promotion of gastric tumorigenesis by FoxM1 directly and significantly correlated with transactivation of vascular endothelial growth factor (VEGF) expression and elevation of angiogenesis. ^ To further investigate the underlying mechanisms that result in FoxM1 overexpression in gastric cancer, I investigated FoxM1 and Krüppel-like factor 4 (KLF4) expressions in primary gastric cancer and normal gastric tissue specimens. Concomitance of increased expression of FoxM1 protein and decreased expression of KLF4 protein was evident in human gastric cancer. Enforced KLF4 expression suppressed FoxM1 protein expression. Moreover, a region within the proximal FoxM1 promoter was identified to have KLF4-binding sites. Finally, I found an increased FoxM1 expression in gastric mucosa of villin-Cre -directed tissue specific Klf4-null mice.^ In summary, I offered both clinical and mechanistic evidence that dysregulated expression of FoxM1 play an important role in gastric cancer development and progression, while KLF4 mediates negative regulation of FoxM1 expression and its loss significantly contributes to FoxM1 dysregulation. ^

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Neural tube defects (NTDs) remain elevated in Hispanic women along the South Texas Border, despite folate supplementation and folate fortification of cereal products. Missmer et al. examined the relationships between fumonisins, a class of corn mycotoxin, and NTDs in Hispanic women who ate corn tortillas and found increased odds ratios with increasing exposure, as measured by serum sphinganine:sphingosine (sa:so) ratios. This study examined the interactions between categorized maternal serum folate levels and stratified sa:so ratios and the resultant odds ratios of NTDs, stratified by type (anencephaly and spina bifida). The hypothesis was that the above normal folate category would have lower odds ratios of NTDs at given sa:so ratio categories and that there would be a difference in odds ratio patterns for anencephaly and spina bifida. Methods. Data for 406 Hispanic women were obtained from the Missmer case-control study. Sa:so ratios were calculated and subjects were stratified into “below normal,” “normal,” and above normal range for folate. A logistic regression model was applied, controlling for BMI, serum B12, lab batch, and conception date. Results. While OR’s of NTDs increased for increasing sa:so ratios, OR’s for “above normal” folate were not decreased at any sa:so ratio and there was no statistically significant difference between OR’s of anencephaly and spina bifida. Conclusion. Folate does not appear to be protective against the potential teratogenic effect of fumonisins and did not differ in effect on OR’s of NTD by type. More research is necessary to determine the extent of fumonisin exposure in Hispanic women along the South Texas Border.^

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Hydrazine $\rm (N\sb2H\sb4),$ an important liquid propellant and derivative chemical for pharmaceuticals and pesticides, produces coma and convulsions sometimes resulting in death. Hyperammonia was found in rabbits exposed to 18 mg/Kg of hydrazine. Results of Part One of this study of rabbits emphasize the importance of acute ammonia toxicity during the first three hours following exposure to hydrazine. At no time during this post exposure period did a significant reduction of hydrazine to ammonia occur. Therefore, the elevated blood ammonia was apparently secondary to the effects of hydrazine on metabolic pathways. Further, the results support the theory of competitive inhibition of ammonia by hydrazine and emphasize the need to monitor plasma ammonia following toxic exposure to hydrazine.^ In Part Two, urea, ammonia, CO$\sb2,$ pH, glucose, sodium, potassium, chloride and creatinine were measured for up to 4 hours following injection of 18 mg/Kg of hydrazine in each of two groups of five rabbits. One group received normal saline and the other group received 5% dextrose and water/normal saline. Hyperammonemia, minimal metabolic acidosis and hyperglycemia without increased urea were found in the rabbits receiving normal saline intravenous infusion and hydrazine injection. Hence, hypoglycemia does not appear to play a role in the development of hyperammonemia. A significant difference in the elevated ammonia levels between the two groups receiving dextrose and water/normal saline and normal saline at 1 hour occurred. There was no significant difference in the elevated ammonia levels seen between the two groups receiving dextrose and water/normal saline and normal saline at 2.5 and 4 hours. Thus at 1 hour the group receiving dextrose was able to utilize excess glucose to detoxify ammonia, while at 2.5 and 4 hours there was no significant difference in the two groups' ability to detoxify ammonia.^ Findings support the theory that hydrazine inhibits the formation of urea resulting in hyperammonemia. Results suggest that hydrazine at 18 mg/Kg, a known hypoglycemic agent, causes serious hyperammonemia without increasing urea production during hyperglycemia. These experiments support a unified theory for the toxic mechanism of action of hydrazine, i.e., the intermediary metabolic effects of hydrazine are brought about by the formation of hydrazones which encumber ATP synthesis and vitamin B$\sb6$ enzymatic reactions. ^

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Triple-negative breast cancers (TNBC) are characterized by the lack of or reduced expression of the estrogen and progesterone receptors, and normal expression of the human epidermal growth factor receptor 2. The lack of a well-characterized target for treatment leaves only systemic chemotherapy as the mainstay of treatment. Approximately 60-70% of patients are chemosensitive, while the remaining majority does not respond. Targeted therapies that take advantage of the unique molecular perturbations found in triple-negative breast cancer are needed. The genes that are frequently amplified or overexpressed represent potential therapeutic targets for triple-negative breast cancer. The purpose of this study was to identify and validate novel therapeutic targets for triple-negative breast cancers. 681 genes showed consistent and highly significant overexpression in TNBC compared to receptor-positive cancers in 2 data sets. For two genes, 3 of the 4 siRNAs showed preferential growth inhibition in TNBC cells. These two genes were the low density lipoprotein receptor-related protein 8 (LRP8) and very low-density lipoprotein receptor (VLDLR). Exposure to their cognate ligands, reelin and apolipoprotein E isoform 4 (ApoE4), stimulated the growth of TNBC cells in vitro. Suppression of the expression of either LRP8 or VLDLR or exposure to RAP (an inhibitor of ligand binding to LRP8 and VLDLR) abolished this ligand-induced proliferation. High-throughput protein and metabolic arrays revealed that ApoE4 stimulation rescued TNBC cells from serum-starvation induced up-regulation of genes involved in lipid biosynthesis, increased protein expression of oncogenes involved in the MAPK/ERK and DNA repair pathways, and reduced the serum-starvation induction of biochemicals involved in oxidative stress response and glycolytic metabolism. shLRP8 MDA-MB-231 xenografts had reduced tumor volume, in comparison to parental and shCON xenografts. These results indicate that LRP8-APOE signaling confers survival advantages to TNBC tumors under reduced nutrient conditions and during cellular environmental stress. We revealed that the LRP8-APOE receptor-ligand system is overexpressed in human TNBC. We also demonstrated that this receptor system mediates a strong growth promoting and survival function in TNBC cells in vitro and helps to sustain the growth of MDA-MD-231 xenografts. We propose that inhibitors of LRP8-APOE signaling may be clinically useful therapeutic agents for triple-negative breast cancer.

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The neuropeptide somatostatin is a widely distributed general inhibitor of endocrine, exocrine, gastrointestinal and neural functions. The biological actions of somatostatin are initiated by interaction with high affinity, plasma membrane somatostatin receptors (sst receptors). Five sst receptor subtypes have been cloned and sequence analysis shows they are all members of the G protein coupled receptor superfamily. The G proteins play a pivotal role in sst receptor signal transduction and the specificity of somatostatin receptor-G protein coupling defines the possible range of cellular responses. However, the data for endogenous sst receptor and G protein coupling is very limited, and even when it is available, the sst receptor subtypes involved in G protein coupling and signal transduction are unknown due to the expression of multiple sst receptor subtypes in target cell lines or tissues of somatostatin.^ In an effort to characterize each individual sst receptor subtypes, antisera against unique C-terminal regions of different sst receptor subtypes have been developed in our lab. In this report, antisera made against the sst1, sst2A and sst4 receptors are characterized. They are highly specific to their corresponding receptors and efficiently immunoprecipitate the sst receptors. Using these antibodies, the cell lines expressing these sst receptor subtypes were identified with both immunoprecipitation and Western blot methods. The development of sst receptor subtype specific antibodies make it possible to determine the specificity of the sst receptor subtype and G protein coupling in target cells or tissues expressing multiple sst receptors, two questions were addressed by this thesis: (1) whether different cellular environments affect receptor subtype and G protein coupling; (2) whether different sst receptors couple to different G proteins in similar cellular environments.^ Taken together our findings, both sst1 and sst2A receptors couple with G$\alpha\sb{\rm i1},$ G$\alpha\sb{\rm i2}$ and G$\alpha\sb{\rm i3}$ in CHO cells, G$\alpha\sb{\rm i2}$ and G$\alpha\sb{\rm i3}$ in GH$\sb4$C$\sb1$ cells. Further, sst2A receptors couple with G$\alpha\sb{\rm i1},$ G$\alpha\sb{\rm i2}$ and G$\alpha\sb{\rm i3}$ in AR4-2J cells while sst4 receptors couple with G$\alpha\sb{\rm i2}$ and G$\alpha\sb{\rm i3}$ in CHO cells. Therefore, the G protein coupling of the same sst receptors in different cell lines is basically similar in that they all couple with multiple $\alpha$-subunits of the G$\rm \sb{i}$ proteins, suggesting cellular environment has little effect on receptor and G protein coupling. Moreover, different sst receptors have similar G protein coupling specificities in the same cell line, suggesting components other than receptor and G$\alpha$ subunits in the signal transduction pathways may contribute to specific functions of each sst receptor subtype. This series of experiments represent a novel approach in dissecting signal transduction pathways and may have general application in the field. Furthermore, this is the first systematic study of sst receptor subtype and G protein $\alpha$-subunit interaction in both transfected cells and in normal cell lines. The information generated will be very useful in our understanding of sst receptor signal transduction pathways and in directing future sst receptor research. ^

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The delta13C and Cd measurements from benthic foraminifera from Biogeochemical Ocean Flux Study (BOFS) northeast Atlantic Ocean sediment cores are presented. The delta13C values in glacial foraminifera are consistent with those from elsewhere in the North Atlantic Ocean. For intermediate water (1000 - 2000 m water depth), delta13C values were higher at the last glacial maximum than in present North Atlantic Deep Water (NADW), whereas for deep water (>2000 m) they were lower during the glacial maximum. The Cd concentrations of glacial northeast Atlantic intermediate water were lower than those of present NADW. However, deepwater Cd concentrations increased to values between NADW and present Pacific Deep Water (PDW). The delta13C and Cd data are consistent and show that the northeast Atlantic Ocean was strongly stratified with 13C enriched, low Cd intermediate water overlying 13C depleted, high Cd deep water. The glacial water column comprised two different water masses: deep water, similar in character to present Antarctic Bottom Water (AABW), and intermediate water, different in character from both AABW and NADW, and any present intermediate-depth North Atlantic water. The characteristics of glacial intermediate water were, however, similar to present near-surface waters in the North Atlantic, which suggests rapid ventilation of the glacial ocean to depths of up to 2000 m by cold, nutrient-depleted young surface waters.

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A mass budget was constructed for organic carbon on the upper slope of the Middle Atlantic Bight, a region thought to serve as a depocenter for fine-grained material exported from the adjacent shelf. Various components of the budget are internally consistent, and observed differences can be attributed to natural spatial variability or to the different time scales over which measurements were made. The flux of organic carbon to the sediments in the core of the depocenter zone, at a water depth of 1000 m, was measured with sediment traps to be 65 mg C m**-2 day**-1, of which 6-24 mg C m**-2 day**-1 is buried. Oxygen fluxes into the sediments, measured with incubation chambers attached to a free vehicle lander, correspond to total carbon remineralization rates of 49-70 mg C m**-2 day**-1. Carbon remineralization rates estimated from gradients of Corg within the mixed layer, and from gradients of dissolved ammonia and phosphate in pore waters, sum to only 4-6 mg C m**-2 day**-1. Most of the Corg remineralization in slope sediments is mediated by bacteria and takes place within a few mm of the sediment-water interface. Most of the Corg deposited on the upper slope sediments is supplied by lateral transport from other regions, but even if all of this material were derived from the adjacent shelf, it represents <2% of the mean annual shelf productivity. This value is further lowered by recognizing that as much as half of the Corg deposited on the slope is refractory, having originated by reworking from older deposits. Refractory Corg arrives at the sea bed with an average 14C age 600-900 years older than the pre-bomb 14C age of DIC in seawater, and has a mean life in the sediments with respect to biological remineralization of at least 1000 years. Labile carbon supplied to the slope, on the other hand, is rapidly and (virtually) completely remineralized, with a mean life of < 1 year. Carbon-14 ages of fine-grained carbonate and organic carbon present within the interstices of shelf sands are consistent with this material acting as a source for the old carbon supplied to the slope. Winnowing and export of reworked carbon may contribute to the often-described relationship between organic carbon preservation and accumulation rate of marine sediments.

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The ubiquitous marine trace gas dimethyl sulfide (DMS) comprises the greatest natural source of sulfur to the atmosphere and is a key player in atmospheric chemistry and climate. We explore the short-term response of DMS production and cycling and that of its algal precursor dimethyl sulfoniopropionate (DMSP) to elevated carbon dioxide (CO2) and ocean acidification (OA) in five 96 h shipboard bioassay experiments. Experiments were performed in June and July 2011, using water collected from contrasting sites in NW European waters (Outer Hebrides, Irish Sea, Bay of Biscay, North Sea). Concentrations of DMS and DMSP, alongside rates of DMSP synthesis and DMS production and consumption, were determined during all experiments for ambient CO2 and three high-CO2 treatments (550, 750, 1000 µatm). In general, the response to OA throughout this region showed little variation, despite encompassing a range of biological and biogeochemical conditions. We observed consistent and marked increases in DMS concentrations relative to ambient controls (110% (28-223%) at 550 µatm, 153% (56-295%) at 750 µatm and 225% (79-413%) at 1000 µatm), and decreases in DMSP concentrations (28% (18-40%) at 550 µatm, 44% (18-64%) at 750 µatm and 52% (24-72%) at 1000 µatm). Significant decreases in DMSP synthesis rate constants (µDMSP /d) and DMSP production rates (nmol/d) were observed in two experiments (7-90% decrease), whilst the response under high CO2 from the remaining experiments was generally indistinguishable from ambient controls. Rates of bacterial DMS gross consumption and production gave weak and inconsistent responses to high CO2. The variables and rates we report increase our understanding of the processes behind the response to OA. This could provide the opportunity to improve upon mesocosm-derived empirical modelling relationships and to move towards a mechanistic approach for predicting future DMS concentrations.

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The distribution of calcareous nannofossils is documented for the middle Eocene through lowermost Miocene cores from Ocean Drilling Program Holes 699A and 703A in the subantarctic South Atlantic. The detailed nannofossil biostratigraphies established, in combination with published magnetostratigraphic data, have provided a fairly detailed age model for each hole. This study suggests that the middle Eocene through lowermost Miocene section from Hole 699A is virtually complete. A major hiatus has been identified in Hole 703A in the earliest Oligocene, coincident with n abrupt cooling in the Southern Ocean. Comparison of the nannofossil datum ages calibrated with magnetostratigraphy in the two holes with those from mid and southern high latitudes demonstrates synchroneity or diachroneity for the following nannofossil datums: (1) The last occurrence (LO) of Reticulofenestra bisecta is a consistent and reliable biostratigraphic marker for the Oligocene/Miocene boundary from mid- to high latitudes but not in extreme high latitudes; (2) similarly, the LO of Chiasmolithus altus has a consistent age of about 26.8 Ma in the Southern Ocean except in the extreme high latitudes where the datum appears to be substantially younger; (3) the LO of Reticulofenestra umbilica is about 32.9 Ma in the Southern Ocean; (4) the LO of Isthmolithus recurvus is reliable and consistent from mid through high latitudes and correlates with the lower part of Subchron C12R (~34.4 Ma); (5) the LO of Reticulofenestra oamaruensis has a consistent age of 36.0 Ma at all four Southern Ocean sites that have yielded a lower Oligocene magnetostratigraphy; (6) the first occurrence (FO) of R. oamaruensis is at 38.4 Ma in the Southern Ocean; and (7) the FO of I. recurvus shows some age variations from mid to high latitudes and the age range is 38.5-39.0 Ma at the five Southern Ocean sites.

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The precision of late Paleocene to middle Eocene nannofossil datums is investigated by means of quantitative methods and correlated to the magnetic polarity stratigraphy, using sequences from the Northwest Pacific, Southeast Atlantic and Italy. It is the rule rather than the exception to find tails of very reduced abundances prior to, or after, a range of consistent and higher abundances. The absolutely first or final occurrence of a species, therefore, seldom provides a synchronous datum when material from different geographic areas are compared. On the other band, synchroneity is often confirmed when the initial sharp rise or the final sharp decline in abundance is used as datum level. The use of datums not employed in the two principal existing nannofossil zonal schemes can substantially improve the biostratigraphic resolution. Two established zonal markers show abundance patterns making them unsuitable as datums: the first occurrences of Ellipsolithus macellus (base NP4, diachronous) and Tribrachiatus nunnii (base NP10 and Paleocene/Eocene boundary, too rare and too short range in open ocean sections). The first occurrence of either Fasciculithus spp. or Sphenolithus spp. is a better marker near the base of NP4. The first occurrence of Discoaster diastypus at 56.6 Ma represents a suitable replacement for recognition of the Paleocene/Eocene boundary.

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New Pb, Sr, and Nd isotope data are presented for 64 samples from the six backarc sites drilled during Leg 135. Systematic changes in Pb and Sr compositions illustrate significant isotopic variations between and within sites as well as provide two key pieces of information. First, a recent influx of asthenosphere with Indian Ocean mantle affinities has occurred and has successfully displaced older "Pacific" asthenosphere from the mantle underlying the backarc region. Second, clear evidence exists for mixing between these two asthenospheric end-members and at least one "arc-like" component. The latter was not the same as most material currently erupting in the Tofua Arc, but it must have had a more radiogenic Pb-isotope signature, perhaps similar to rocks analyzed from the islands of Tafahi, and Niuatoputapu. A comparison between the isotopic variations and the tectonic setting of the drill sites reveals consistent and important information regarding the mantle dynamics beneath the evolving backarc basin. We propose a model in which the source of upwelling magmas changes from Pacific to Indian Ocean asthenosphere with the propagation of seafloor spreading, a model with important implications for the rate of mantle influx into this region. Although the chemistries of backarc magmas have been profoundly influenced by this process, an additional consequence is the advection of Indian Ocean asthenosphere into the sub-arc mantle source. The isotopic compositions of arc rocks from the vicinity have been reevaluated on the basis of the proposed mantle advection model. We suggest that the slab-derived flux of trace elements into the arc wedge has remained relatively uniform with time (i.e., ~40 Ma), so that the change in arc chemistry results from mantle source substitution, rather than from differences in the composition of the downgoing plate.

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Most current methods of reconstructing past sea levels within Antarctica rely on radiocarbon dating. However, radiocarbon dating is limited by the availability of material for dating and problems inherent with radiocarbon reservoirs in Antarctic marine systems. Here we report on the success of a new approach to dating raised beach deposits in Antarctica for the purpose of reconstructing past sea levels. This new approach is the use of optically stimulated luminescence (OSL) on quartz-grains obtained from the underside of cobbles within raised beaches and boulder pavements. We obtained eight OSL dates from three sites along the shores of Maxwell Bay in the South Shetland Islands of the Antarctic Peninsula. These dates are internally consistent and fit well with previously published radiocarbon ages obtained from the same deposits. In addition, when the technique was applied to a modern beach, it resulted in an age of zero. Our results suggest that this method will provide a valuable tool in the reconstruction of past sea levels in Antarctica and other coarse-grained beach deposits across the globe.

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Monitoring the impact of sea storms on coastal areas is fundamental to study beach evolution and the vulnerability of low-lying coasts to erosion and flooding. Modelling wave runup on a beach is possible, but it requires accurate topographic data and model tuning, that can be done comparing observed and modeled runup. In this study we collected aerial photos using an Unmanned Aerial Vehicle after two different swells on the same study area. We merged the point cloud obtained with photogrammetry with multibeam data, in order to obtain a complete beach topography. Then, on each set of rectified and georeferenced UAV orthophotos, we identified the maximum wave runup for both events recognizing the wet area left by the waves. We then used our topography and numerical models to simulate the wave runup and compare the model results to observed values during the two events. Our results highlight the potential of the methodology presented, which integrates UAV platforms, photogrammetry and Geographic Information Systems to provide faster and cheaper information on beach topography and geomorphology compared with traditional techniques without losing in accuracy. We use the results obtained from this technique as a topographic base for a model that calculates runup for the two swells. The observed and modeled runups are consistent, and open new directions for future research.

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We report an investigation of the effects of increases in pCO2 on the survival, growth and molecular physiology of the neritic amphipod Gammarus locusta which has a cosmopolitan distribution in estuaries. Amphipods were reared from juvenile to mature adult in laboratory microcosms at three different levels of pH in nominal range 8.1-7.6. Growth rate was estimated from weekly measures of body length. At sexual maturity the amphipods were sacrificed and assayed for changes in the expression of genes coding for a heat shock protein (hsp70 gene) and the metabolic enzyme glyceraldehyde-3-phosphate dehydrogenase (gapdh gene). The data show that the growth and survival of this species is not significantly impacted by a decrease in sea water pH of up to 0.5 units. Quantitative real-time PCR analysis indicated that there was no significant effect of growth in acidified sea water on the sustained expression of the hsp70 gene. There was a consistent and significant increase in the expression of the gapdh gene at a pH of ~7.5 which, when combined with observations from other workers, suggests that metabolic changes may occur in response to acidification. It is concluded that sensitive assays of tissue physiology and molecular biology should be routinely employed in future studies of the impacts of sea water acidification as subtle effects on the physiology and metabolism of coastal marine species may be overlooked in conventional gross "end-point" studies of organism growth or mortality.