Effect of branched-chain amino acids on muscle atrophy in cancer cachexia

In the present study, the BCAAs (branched-chain amino acids) leucine and valine caused a significant suppression in the loss of body weight in mice bearing a cachexia-inducing tumour (MAC16), producing a significant increase in skeletal muscle wet weight, through an increase in protein synthesis and a decrease in degradation. Leucine attenuated the increased phosphorylation of PKR (double-stranded-RNA-dependent protein kinase) and eIF2α (eukaryotic initiation factor 2α) in skeletal muscle of mice bearing the MAC16 tumour, due to an increased expression of PP1 (protein phosphatase 1). Weight loss in mice bearing the MAC16 tumour was associated with an increased amount of eIF4E bound to its binding protein 4E-BP1 (eIF4E-binding protein 1), and a progressive decrease in the active eIF4G-eIF4E complex due to hypophosphorylation of 4E-BP1. This may be due to a reduction in the phosphorylation of mTOR (mammalian target of rapamycin), which may also be responsible for the decreased phosphorylation of p70S6k (70 kDa ribosomal S6 kinase). There was also a 5-fold increase in the phosphorylation of eEF2 (eukaryotic elongation factor 2), which would also decrease protein synthesis through a decrease in translation elongation. Treatment with leucine increased phosphorylation of mTOR and p70S6k, caused hyperphosphorylation of 4E-BP1, reduced the amount of 4E-BP1 associated with eIF4E and caused an increase in the eIF4G-eIF4E complex, together with a reduction in phosphorylation of eEF2. These changes would be expected to increase protein synthesis, whereas a reduction in the activation of PKR would be expected to attenuate the increased protein degradation. © The Authors.

Cancer cachexia

Purpose of review: Although cachexia has a major effect on both the morbidity and mortality of cancer patients, information on the mechanisms responsible for this condition is limited. This review summarizes recent data in this area. Recent findings: Cachexia is defined as loss of muscle, with or without fat, frequently associated with anorexia, inflammation and insulin resistance. Loss of adipose mass is due to an increased lipolysis through an increased expression of hormone-sensitive lipase. Adipose tissue does not contribute to the inflammatory response. There is an increased phosphorylation of both protein kinase R (PKR) and eukaryotic initiation factor 2 on the α-subunit in skeletal muscle of cachectic cancer patients, which would lead to muscle atrophy through a depression in protein synthesis and an increase in degradation. Mice lacking the ubiquitin ligase MuRF1 are less susceptible to muscle wasting under amino acid deprivation. Expression of MuRF1 and atrogin-1 is increased by oxidative stress, whereas nitric oxide may protect against muscle atrophy. Levels of interleukin (IL)-6 correlate with cachexia and death due to an increase in tumour burden. Ghrelin analogues and melanocortin receptor antagonists increase food intake and may have a role in the treatment of cachexia. Summary: These findings provide impetus for the development of new therapeutic agents. © 2010 Wolters Kluwer Health

Are tumoral factors responsible for host tissue wasting in cancer cachexia?

Both cytokines and tumor factors have been implicated in tissue loss in cancercachexia. Loss of adipose tissue is most likely due to the tumor (and host) factorzinc-α2-glycoprotein because of its direct lipolytic effect, ability to sensitizeadipocytes to lipolytic stimuli and increased expression in cachexia. TNF-α andthe tumor factor proteolysis-inducing factor are the major contenders for skeletalmuscle at rophy; both increase protein degradat ion through theubiquitin-proteasome pathway and depres s protein synthesis throughphosphorylation of eukaryotic initiation factor 2α. However, while most studiesreport proteolysis-inducing factor levels to correlate with the appearance ofcachexia, there is some disagreement regarding a correlation between serumlevels of TNF-α and weight loss. Furthermore, only antagonists to proteolysisinducingfactor prevent muscle loss in cancer patients, suggesting that tumorfactors are the most important. © 2010 Future Medicine Ltd.

The Nrf2-ARE activation protect neurones against oxidative stress

Oxidative stress has been implicated in the pathogenesis of many neurodegenerative diseases including Alzheimer’s disease. The transcription factor, Nrf2 (nuclear factor E2-related factor 2) that binds to the antioxidant responsive element (ARE) activates a battery of genes encoding enzymes and factors essential for neuronal survival. We have investigated the hypothesis that a downstream product of cyclooxygenase(COX-2), 15-deoxy-delta (12, 14)-prostagland in J2 (15d-PGJ2) has protective effects by activating the Nrf2 pathway during oxidative stress.Human neuroblastoma cells (SHSY5Y) were differentiated intoneuronal-like cells as described previously (Gimenez-Cassina et al.,2006). SHSY5Y cells were co-treated with 10 mM buthionine sulfoximine (BSO) 7 10 mM 15d-PGJ2. Cell viability was measured by MTT assay and cellular glutathione (GSH) levels were measured after treating cells for0.5-24 hours by GSH recycling assay. Cellular Nrf2 levels were determined by immunoblotting. IL-6 levels were measured by ELISA.15d-PGJ2 alone lowered GSH levels 30min after the treatment(12.870.64 nmol/mg protein) and returned to untreated control levels at 16hours (28.173.6 nmol/mg protein; Po0.01). Compared to intracellular GSH levels in untreated cells (27.871.8 nmol/mg protein) BSO treatment alone significantly decreased GSH (9.672.1 nmol/mg protein;Po0.001) but co-incubation with 15d-PGJ2 for 24 hours prevented the depletion elicited by BSO(21.372.7 nmol/mg protein). Compared to untreated cells BSO treatment decrease dIL-6 secretion (from 0.941.6ng/ml to 0.6971.3ng/ml) and total Nrf2 protein levels (by21%). Co-incubation with15d-PGJ2 for 24 hours with BSO did not change IL-6(0.6771.4ng/ml) or total Nrf2 level at any time point. This study suggests that neuronal toxicity resulting from glutathione depletion canbere stored by the induction of Nrf2-ARE pathway and the role of the Nrf2 signalling merits further investigation in neurodegenerative diseases.

Development of an instrument to measure high school students' global awareness and attitudes: Looking through the lens of social sciences

The purpose of this study was to develop an instrument to measure high school students’ perspectives on global awareness and attitudes toward social issues. The research questions that guided this study were: (a) Can acceptable validity and reliability estimates be established for an instrument developed to measure high schools students' global awareness? (b) Can acceptable validity and reliability estimates be established for an instrument developed to measure high schools students' attitudes towards global social issues? (c) What is the relationship between high school students’ GPA, race/ethnicity, gender, socio-economic status, parents’ education, getting the news, reading and listening habits, the number of classes taken in the social sciences, whether they speak a second language, and have experienced living in or visiting other countries, and their perception of global awareness and attitudes toward global social issues. ^ An ex post facto research design was used and the data were collected using a 4-part Likert-type survey. It was administered to 14 schools in the Miami-Dade County, Florida area to 704 students. A factor analysis with an orthogonal varimax rotation was vii used to select the factors that best represented the three constructs – global education, global citizenship, and global workforce. This was done to establish construct validity. Cronbach’s alpha was used to determine the reliability of the instrument. Descriptive statistics and a hierarchical multiple regression were used for the demographics to establish their relationship, if any, to the findings. ^ Key findings of the study were that reliable and valid estimates can be developed for the instrument. The multiple regression analysis for model 1 and 2 accounted for a variance of 3% and 5% for self-perceptions of global awareness (factor 1). The regression model also accounted for a 5% and 13% variance in the two models for attitudes toward global social issues (factor 2). The demographics that were statistically significant were: ethnicity, gender, SES, parents’ education, listening to music, getting the news, speaking a second language, GPA, classes taken in the social sciences, and visiting other countries. An important finding for the study was those attending public schools (as opposed to private schools) had more positive attitudes towards global social issues (factor 2) The statistics indicated that these students had taken history, economics, and social studies – a curriculum infused with global perspectives.^

The effect of young adult literature on adolescents' rape myth acceptance

This quasi-experimental study (N = 139) measured the effect of a reader response based instructional unit of the novel Speak on adolescents' rape myth acceptance. Participants were eighth grade language arts students at a Title I middle school in a major metropolitan school district. Seven classes were randomly assigned to treatment ( n = 4) or control (n = 3) condition. Two teachers participated in the study and both taught both treatment and control classes. The study lasted a period of five weeks. Participants were pretested using the Rape Myth Acceptance Scale (Burt, 1980) and a researcher created scale, the Adolescent Date Rape Scale (ADRMS). Analysis of pretests showed the ADRMS to be a reliable and valid measure of rape myth acceptance in adolescents. Factor analysis revealed it to have two major components: "She Wanted It" and "She Lied." Pretests supported previous studies which found girls to have significantly lower initial levels of rape myth acceptance than boys (p < .001). A 2 (group) x 2 (instructor) x 2 (sex) ANCOVA using ADRMS pretest as a covariate and ADRMS posttest as a dependent variable found that treatment was effective in reducing rape myth acceptance (p < .001, η2 = .15). Boys with high rape myth acceptance as demonstrated by pretest scores of 1 standard deviation above the mean on ADRMS did not have a backlash to treatment. Extended analysis revealed that participants had significantly lower scores posttest on Factor 1, "She Wanted It" (p < .001, η2 = .27), while scores on Factor 2, "She Lied" were not significantly lower (p = .07). This may be because the content of the novel primarily deals with issues questioning whether the main characters assault was a rape rather than a false accusation. Attrition rates were low (N = 15) and attrition analysis showed that drop outs did not significantly alter the treatment or control groups. Implications for reader response instruction of young adult literature, for research on rape myth acceptance in secondary schools, and for statistical analysis of effect size using pretests as filters are discussed.

Occupational therapists' attitudes toward family -centered care

The purpose of this study was to examine pediatric occupational therapists attitudes towards family-centered care. Specific attributes identified by the literature (professional characteristics, educational experiences and organizational culture) were investigated to determine their influence on these attitudes. Study participants were 250 pediatric occupational therapists who were randomly selected from the American Occupational Therapy Association special interest sections. ^ Participants received a mail packet with three instruments to complete and mail back within 2 weeks. The instruments were (a) the Professional Attitude Scale, (b) the Professional Characteristics Questionnaire, and (c) the Family-Centered Program Rating Scale. There was a 50% return rate. Data analysis was conducted in SPSS using descriptive statistics, correlations and regression analysis. ^ The analysis showed that pediatric occupational therapists working in various practice settings demonstrate favorable attitudes toward family-centered care as measured by the Professional Attitude Scale. There was no correlation between professional characteristics and educational experiences to therapists' attitudes. A moderate correlation (r = .368, p < .05) was found between the occupational therapists attitudes and the organizational culture of their workplaces. A factor analysis was conducted on the organizational culture instrument (FamPRS) as this sample was exclusively pediatric occupational therapists and the original sample was interdisciplinary professionals. Two factors were extracted using a principal components extraction and varimax rotation, in addition to examination of the scree plot. These two factors accounted for 50% of the total variance of the scores on the instrument. Factor 1, called empowerment accounted for 45.6% of the variance, and Factor 2, responsiveness accounted for 4.3% of the variance of the entire instrument. Stepwise regression analysis demonstrated that these two factors accounted for 16% of the variance toward attitudes clinicians hold toward family-centered care. These factors support the tenets of family-centered care; empowering parents to be leaders in their child's health care and helping organizations become more responsive to family needs. ^ These study findings suggest that organizational culture has some influence on occupational therapists attitudes toward family-centered care (R 2 = .16). These findings suggest educators should consider families as valuable resources when considering program planning in family-centered care at preservice and workplace settings. ^

Lithostratigraphy determined from downhole logs in the AND-2A borehole

During the 2007-2008 austral spring season, the ANDRILL (Antarctic Drilling project) Southern McMurdo Sound Project recovered an 1138-m-long core, representing the last 20 m.y. of glacial history. An extensive downhole logging program was successfully carried out. Due to drill hole conditions, logs were collected in several passes from the total depth at 1138.54 m below seafloor (mbsf) to 230 mbsf. After data correction, several statistical methods, such as factor analysis, cluster analysis, box-and-whisker diagrams, and cross-plots, were applied. The aim of these analyses was to use detailed interpretation of the downhole logs to obtain a description of the lithologies and their specific physical properties that is independent of the core descriptions. The sediments were grouped into the three main facies, diamictite, mudstone and/or siltstone, and sandstone, and the physical properties of each were determined. Notable findings include the high natural radioactivity values in sandstone and the high and low magnetic susceptibility values in mudstone and/or siltstone and in sandstone. A modified lithology cluster column was produced on the basis of the downhole logs and statistical analyses. It was possible to use the uranium content in the downhole logs to determine hiatuses and thus more accurately place the estimated hiatuses. Using analyses from current literature (geochemistry, clasts, and clay minerals) in combination with the downhole logs (cluster analysis), the depths 225 mbsf, 650 mbsf, 775 mbsf, and 900 mbsf were identified as boundaries of change in sediment composition, provenance, and/or environmental conditions. The main use of log interpretation is the exact definition of lithological boundaries and the modification of the paleoenvironmental interpretation.

Benthic foraminifera in eastern equatorial Indian Ocean surface sediments

Study of Recent abyssal benthic foraminifera from core-top samples in the eastern equatorial Indian Ocean has identified distinctive faunas whose distribution patterns reflect the major hydrographic features of the region. Above 3800 m, Indian Deep Water (IDW) is characterized by a diverse and evenly-distributed biofacies to which Globocassidulina subglobosa, Pyrgo spp., Uvigerina peregrina, and Eggerella bradyi are the major contributors. Nuttalides umbonifera and Epistominella exigua are associated with Indian Bottom Water (IBW) below 3800 m. Within the IBW fauna, N. umbonifera and E. exigua are characteristic of two biofacies with independent distribution patterns. Nuttalides umbonifera systematically increases in abundance with increasing water depth. The E. exigua biofacies reaches its greatest abundance in sediments on the eastern flank of the Ninetyeast Ridge and in the Wharton-Cocos Basin. The hydrographic transition between IDW and IBW coincides with the level of transition from waters supersaturated to waters undersaturated with respect to calcite and with the depth of the lysocline. Carbonate saturation levels, possibly combined with the effects of selective dissolution on the benthic foraminiferal populations, best explain the change in faunas across the IDW/IBW boundary and the bathymetric distribution pattern of N. umbonifera. The distribution of the E. exigua fauna cannot be explained with this model. Epistominella exigua is associated with the colder, more oxygenated IBW of the Wharton-Cocos Basin. The distribution of this biofacies on the eastern flank of the Ninetyeast Ridge agrees well with the calculated bathymetric position of the northward flowing deep boundary current which aerates the eastern basins of the Indian Ocean.

Benthic foraminifera in Southwest Indian Ocean surface sediments

The distribution of deep-sea benthonic foraminifera in core top samples from the southwest Indian Ocean is examined. Principal component analysis reveals two major assemblages. One assemblages between 3600 and 4800-m water depth is dominated by Episominella umbonifera and is associated with cold (Theta = -0.3 to 0.8°C), low salinity (34.66 to 34.72 * 10**-3) Antarctic Bottom Water in the Crozet Basin, in fracture zones, and on the flanks of the Southwest Indian Ridge. A second assemblage, dominated by Planulina wuellerstorfi, Globocassidulina subglobasa, Astrononion echolsi and Pullenia bulloides, is between 1600 and 3800 m on the Crozet Plateau, Madagascar Ridge, Central Indian Ridge, and Southwest Indian Ridge and is associated with relatively warm (Theta = 0.8 to 2.6°C), high salinity (34.72 to 34.76 * 10**-3) North Atlantic Deep Water. The third principal component divides the P. wuellerstorfi assemblage into two subgroups. One is dominated by Epistominella exigua, P. bulloides, P. wuellerstorfi, and A. echolsi and a second is dominated by G. subglobosa. The distribution of the E. umbonifera assemblage and previous hydrographic studies suggest that AABW flows as a western boundary contour current in the Crozet Basin and penetrates fracture zones in the Southwest Indian Ridge between 55 and 57°E and near 66°E as it travels northward into the Madagascar and Mascarene basins. The faunal-water mass associations from the southeast Indian Ocean are compared; the most notable faunal difference is the absence of Uvigerina as a dominant taxon in the southwest Indian Ocean. A comparison of dissolved oxygen and Uvigerina data shows that oxygen is not a major influence upon the distribution of Uvigerina. A correlation analysis of the faunal data and water depth, potential temperature, in situ temperature, salinity, dissolved oxygen, and 1 - Omega, an index of calcium carbonate undersaturation, was carried out to determine the relationships between fauna and hydrography. The second principal component has a significant positive correlation at the 99.9% level with temperature and negative correlations with water depth and 1 - Omega. A general faunal-water mass correlation exists, but it is not possible to determine which variable controls the faunal distributions.

Benthic foraminifera of the Red Sea

The distribution of living (Rose Bengal-stained), dead and fossil benthic foraminifera was investigated in six short cores (multicores, 30-32 cm total length) recovered from the central Red Sea. The ecological preferences as well as the relationship between the live and dead/fossil assemblages (preserved down-core) were examined. The sites, located along a W-E profile and between the depth of 366 and 1782 m, extend from the center of the oxygen minimum zone (OMZ, ~200-650 m), through its margin at ~600 m, and down to the well-aerated deep-water environment. Live (Rose-Bengal stained) and coexisting dead foraminifera were studied in the upper 5 cm of each of the sites, and the fossil record was studied down to ~32 cm. Q-mode Principal Component Analysis was used and four distinct foraminiferal fossil assemblages were determined. These assemblages follow different water mass properties. In the center of the OMZ, where the organic carbon content is highest and the oxygen concentration is lowest (<=0.5 ml O2/l), the Bolivina persiensis-Bulimina marginata-Discorbinella rhodiensis assemblage dominates. The slightly more aerated and lower organic-carbon-content seafloor, at the margin of the OMZ, is characterized by the Neouvigerina porrecta-Gyroidinoides cf. G. soldanii assemblage. The transitional environment, between 900-1200 m, with its well-aerated and oligotrophic seafloor, is dominated by the Neouvigerina ampullacea-Cibicides mabahethi assemblage. The deeper water (>1500 m), characterized by the most oxygenated and oligotrophic seafloor conditions, is associated with the Astrononion sp. A-Hanzawaia sp. A assemblage. Throughout the Red Sea extremely high values of temperature and salinity are constant below ~200 m depth, but the flux of organic matter to the sea floor varies considerably with bathymetry and appears to be the main controlling factor governing the distribution pattern of the benthic foraminifera. Comparison between live and the dead/fossil assemblages reveals a large difference between the two. Processes that may control this difference include species-specific high turnover rates, and preferential predation and loss of fragile taxa (either by chemical or microbial processes). Significant variations in the degree of loss of the organic-cemented agglutinants were observed down core. This group is preserved down to 5-10 cm at the shallow OMZ sites and down to greater depths at well-aerated and oligotrophic sites. The lower rate of disintegration of these forms, in the deeper locations of the Red Sea, may be related to low microbial activity. This results in the preservation of increasing numbers of organic-cemented shells down-core.

Benthic foraminiferal record from Santa Barbara basin

The oxygen minimum zone (OMZ) of the late Quaternary California margin experienced abrupt and dramatic changes in strength and depth in response to changes in intermediate water ventilation, ocean productivity, and climate at orbital through millennial time scales. Expansion and contraction of the OMZ is exhibited at high temporal resolution (107-126 year) by quantitative benthic foraminiferal assemblage changes in two piston cores forming a vertical profile in Santa Barbara Basin (569 m, basin floor; 481 m, near sill depth) to 34 and 24 ka, respectively. Variation in the OMZ is quantified by new benthic foraminiferal groupings and new dissolved oxygen index based on documented relations between species and water-mass oxygen concentrations. Foraminiferal-based paleoenvironmental assessments are integrated with principal component analysis, bioturbation, grain size, CaCO3, total organic carbon, and d13C to reconstruct basin oxygenation history. Fauna responded similarly between the two sites, although with somewhat different magnitude and taxonomic expression. During cool episodes (Younger Dryas and stadials), the water column was well oxygenated, most strongly near the end of the glacial episode (17-16 ka; Heinrich 1). In contrast, the OMZ was strong during warm episodes (Bølling/Allerød, interstadials, and Pre-Boreal). During the Bølling/Allerød, the OMZ shoaled to <360 m of contemporaneous sea level, its greatest vertical expansion of the last glacial cycle. Assemblages were then dominated by Bolivina tumida, reflecting high concentrations of dissolved methane in bottom waters. Short decadal intervals were so severely oxygen-depleted that no benthic foraminifera were present. The middle to late Holocene (6-0 ka) was less dysoxic than the early Holocene.

Paleotemperature and productivity reconstruction of sediment core D11957P on the Iberian Margin

Foraminifera counts and climatic assemblages from the Tore Seamount are used to approach the glacial and interglacial changes in temperature and productivity on the Iberian Margin over the last 225 kyr. Chronostratigraphy is based on Globigerinoides ruber and Globigerina bulloides oxygen isotopes and supported by foraminifera and carbonate stadial fluctuations. Foraminifera indicate cooling from late interglacial stage 5 to the beginning of Termination I (TI). Neogloboquadnna pachyderma-s reflects cold conditions during glacial stages 4-2. In contrast, glacial stage 6 is dominated by warmer N. pachyderma-d and dutertrei and a restricted arctic assemblage. Past sea surface temperatures confirm the general cooling, reaching 4.3°C (SIMMAX.28) during stage 2. Multiple productivity proxies such as organic carbon, productivity-related foraminifera, and delta13C constrain the changes observed. A productivity increase occurs after interglacial stage 5, enhanced from late glacial stage 3 to TI Present-day satellite-detected phytoplankton plumes off Portugal would have accounted in the past glacial stages for the general productivity increase over the Tore. On top of this, welldefined peaks of organic carbon and productivity-related foraminifera correspond with Heinrich events 1-4.