The rockefeller university

A full-length cDNA encoding a putative aspartic acid protease (AcAP1) was isolated for the first time from the flesh of pineapple (Ananas comosus) fruit. The deduced sequence of AcAP1 showed all the common features of a typical plant aspartic protease phytepsin precursor. Analysis of AcAP1 gene expression under postharvest chilling treatment in two pineapple varieties differing in their resistance to blackheart development revealed opposite trends. The resistant variety showed an up-regulation of AcAP1 precursor gene expression whereas the susceptible showed a down-regulation in response to postharvest chilling treatment. The same trend was observed regarding specific AP enzyme activity in both varieties. Taken together our results support the involvement of AcAP1 in postharvest chilling stress resistance in pineapple fruits. (C) 2013 Elsevier GmbH. All rights reserved.

Climate warming has been linked to an apparent general decrease in body sizes of ectotherms, both across and within taxa, especially in aquatic systems. Smaller body size in warmer geographical regions has also been widely observed. Since body size is a fundamental determinant of many biological attributes, climate-warming-related changes in size could ripple across multiple levels of ecological organization. Some recent studies have questioned the ubiquity of temperature-size rules, however, and certain widespread and abundant taxa, such as diatoms, may be important exceptions. We tested the hypothesis that diatoms are smaller at warmer temperatures using a system of geothermally heated streams. There was no consistent relationship between size and temperature at either the population or community level. These field data provide important counterexamples to both James' and Bergmann's temperature-size rules, respectively, undermining the widely held assumption that warming favours the small. This study provides compelling new evidence that diatoms are an important exception to temperature-size rules for three reasons: (i) we use many more species than prior work; (ii) we examine both community and species levels of organization simultaneously; (iii) we work in a natural system with a wide temperature gradient but minimal variation in other factors, to achieve robust tests of hypotheses without relying on laboratory setups, which have limited realism. In addition, we show that interspecific effects were a bigger contributor to whole-community size differences, and are probably more ecologically important than more commonly studied intraspecific effects. These findings highlight the need for multispecies approaches in future studies of climate warming and body size.

The neuroprotective action of dehydroepiandrosterone (DHEA) in the absence of a known specific receptor has been attributed to its metabolism by different cell types in the brain, to various steroids, with a preference to its 7-hydroxylated products. The (EC)-C-t cerebellar granule cell line converts DHEA almost exclusively to 7 alpha-hydroxy-DHEA (7 alpha-OH-DHEA). It has been postulated that DHEA's 7-OH and 7-oxo metabolites can decrease glucocorticoid levels by an interactive mechanism involving 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). In order to study the relationship of 7-hydroxylation of DHEA and glucocorticoid metabolism in intact brain cells, we examined whether (EC)-C-t cerebellar neurons, which are avid producers of 7 alpha-OH-DHEA, could also metabolize glucocorticoids. We report that (EC)-C-t neuronal cells exhibit 11 beta-HSD1 reductase activity, and are able to convert 11-dehydrocorticosterone into corticosterone, whereas they do not demonstrate 11 beta-HSD2 dehydrogenase activity. Consequently, (EC)-C-t cells incubated with DHEA did not yield 7-oxo- or 7 beta-OH-DHEA. Our findings are supported by the reductive environment of (EC)-C-t cells through expression of hexose-6-phosphate dehydrogenase (H6PDH), which fosters 11 beta-HSD1 reductase activity. To further explore the role of 7 alpha-OH-DHEA in (EC)-C-t neuronal cells, we examined the effect of preventing its formation using the CYP450 inhibitor ketoconazole. Treatment of the cells with this drug decreased the yield of 7 alpha-OH-DHEA by about 75% without the formation of alternate DHEA metabolites, and had minimal effects on glucocorticoid conversion. Likewise, elevated levels of corticosterone, the product of 11 beta-HSD1, had no effect on the metabolic profile of DHEA. This study shows that in a single population of whole-cells, with a highly reductive environment, 7 alpha-OH-DHEA is unable to block the reducing activity of 11 beta-HSD1, and that 7-hydroxylation of DHEA does not interfere with the activation of glucocorticoids. Our investigation on the metabolism of DHEA in (EC)-C-t neuronal cells suggest that other alternate mechanisms must be at play to explain the in vivo anti-glucocorticoid properties of DHEA and its 7-OH-metabolites. (C) 2013 Elsevier Ltd. All rights reserved.

Background: The incidence and risk of unique toxicities associated with a multi-targeted tyrosine kinase inhibitor sunitinib, such as hypertension and thromboembolic events, have been previously reported. However, the incidence and risk of hematologic toxicities have been less well characterized. We performed an up-to-date meta-analysis of trials to evaluate the risk of sunitinib-related hematologic toxicities. Methods: We searched Medline and the American Society of Clinical Oncology online database of meeting abstracts up to July 2012 for relevant clinical trials. Eligible studies included phase II and III trials and expanded access programs of sunitinib that reported adequate safety data profile reporting neutropenia, thrombocytopenia or anemia. The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated. Results: A total of 8,526 patients from 60 trials of sunitinib as a single agent revealed that the incidence of sunitinib-associated all-grade and high-grade (Grades 3 and 4) hematologic toxicities were, respectively: neutropenia: 42.1% and 12.8%; thrombocytopenia: 44.7% and 10.7% and anemia: 50.4% and 6.2%. Sunitinib-treated patients (2667 subjects from 10 randomized trials) had a significantly increased risk of all-grade (RR = 3.58; 95% CI, 1.71-7.49) and high-grade (RR = 3.32; 95% CI, 1.60-6.90) neutropenia, all-grade (RR = 4.59; 95% CI, 2.76-7.63) and high-grade (RR = 5.84; 95% CI, 2.22-15.41) thrombocytopenia and all-grade anemia (RR = 1.15; 95% CI, 1.00-1.31). Conclusions: Sunitinib is associated with a significant increase in the risk of developing all-grade and high-grade neutropenia and thrombocytopenia and all-grade anemia compared with control. (C) 2013 Elsevier Ltd. All rights reserved.

Asymmetric cell divisions (ACDs) result in two unequal daughter cells and are a hallmark of stemcells. ACDs can be achieved either by asymmetric partitioning of proteins and organelles or by asymmetric cell fate acquisition due to the microenvironment in which the daughters are placed. Increasing evidence suggests that in the mammalian epidermis, both of these processes occur. During embryonic epidermal development, changes occur in the orientation of the mitotic spindle in relation to the underlying basement membrane. These changes are guided by conserved molecular machinery that is operative in lower eukaryotes and dictates asymmetric partitioning of proteins during cell divisions. That said, the shift in spindle alignment also determines whether a division will be parallel or perpendicular to the basement membrane, and this in turn provides a differential microenvironment for the resulting daughter cells. Here, we review how oriented divisions of progenitors contribute to the development and stratification of the epidermis.

Defense against infection by Mycobacterium tuberculosis (Mtb) is mediated by CD4 T cells. CCR2(+) inflammatory monocytes (IMs) have been implicated in Mtb-specific CD4 T cell responses but their in vivo contribution remains unresolved. Herein, we show that transient ablation of IMs during infection prevents Mtb delivery to pulmonary lymph nodes, reducing CD4 T cell responses. Transfer of MHC class II-expressing IMs to MHC class II-deficient, monocyte-depleted recipients, while restoring Mtb transport to mLNs, does not enable Mtb-specific CD4 T cell priming. On the other hand, transfer of MHC class II-deficient IMs corrects CD4 T cell priming in monocyte-depleted, MHC class II-expressing mice. Specific depletion of classical DCs does not reduce Mtb delivery to pulmonary lymph nodes but markedly reduces CD4 T cell priming. Thus, although IMs acquire characteristics of DCs while delivering Mtb to lymph nodes, cDCs but not moDCs induce proliferation of Mtb-specific CD4 T cells.

The results of a search for the bottomonium counterpart, denoted as X-b, of the exotic charmonium state X(3872) is presented. The analysis is based on a sample of pp collisions at,root s = 8 TeV collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 20.7 fb(-1). The search looks for the exclusive decay channel X-b -> Upsilon(1S)pi(+)pi(-) followed by Upsilon(1S) -> mu(+)mu(-). No evidence for an X-b signal is observed. Upper limits are set at the 95% confidence level on the ratio of the inclusive production cross sections times the branching fractions to Upsilon(1S)pi(+)pi(-) of the X-b and the Upsilon(2S). The upper limits on the ratio are in the range 0.9-5.4% for X-b masses between 10 and 11 GeV. These are the first upper limits on the production of a possible X-b at a hadron collider. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved.

Long-lived antibody memory is mediated by the combined effects of long-lived plasma cells (PCs) and memory B cells generated in response to T cell-dependent antigens (Ags). IL-10 and IL-21 can activate multiple signaling pathways, including STAT1, STAT3, and STAT5; ERK; PI3K/Akt, and potently promote human B cell differentiation. We previously showed that loss-of-function mutations in STAT3, but not STAT1, abrogate IL-10- and IL-21-mediated differentiation of human naive B cells into plasmablasts. We report here that, in contrast to naive B cells, STAT3-deficient memory B cells responded to these STAT3-activating cytokines, differentiating into plasmablasts and secreting high levels of IgM, IgG, and IgA, as well as Ag-specific IgG. This was associated with the induction of the molecular machinery necessary for PC formation. Mutations in IL21R, however, abolished IL-21-induced responses of both naive and memory human B cells and compromised memory B cell formation in vivo. These findings reveal a key role for IL-21R/STAT3 signaling in regulating human B cell function. Furthermore, our results indicate that the threshold of STAT3 activation required for differentiation is lower in memory compared with naive B cells, thereby identifying an intrinsic difference in the mechanism underlying differentiation of naive versus memory B cells.