PGE2-induced colon cancer growth is mediated by mTORC1.

The inflammatory prostaglandin E2 (PGE2) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE2 directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE2-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE2 increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE2 EP4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE2-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE2 increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE2 mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth.

Transforming growth factor beta 1 production by CD4+ CD25+ regulatory T cells in peripheral blood mononuclear cells from healthy subjects stimulated with Leishmania guyanensis.

Transforming growth factor beta (TGF-beta) has been shown to be a central immunomodulator used by leishmaniae to escape effective mechanisms of protection in human and murine infections with these parasites. However, all the information is derived from studies of established infection, while little is known about TGF-beta production in response to Leishmania stimulation in healthy subjects. In this study, TGF-beta1 production was demonstrated in peripheral blood mononuclear cells from healthy subjects never exposed to leishmaniae in response to live Leishmania guyanensis, and the TGF-beta1-producing cells were described as a distinct subpopulation of CD4(+) CD25(+) regulatory T cells. The suppressive properties of CD4(+) CD25(+) T cells were demonstrated in vitro by their inhibition of production of interleukin 2 (IL-2) and IL-10 by CD4(+) CD25(-) T cells in the presence of either anti-CD3 or L. guyanensis. Although neutralization of TGF-beta1 did not reverse the suppressive activity of CD4(+) CD25(+) T cells activated by anti-CD3, it reversed the suppressive activity of CD4(+) CD25(+) T cells activated by L. guyanensis. Altogether our data demonstrated that TGF-beta1 is involved in the suppressive activity of L. guyanensis-stimulated CD4(+) CD25(+) T cells from healthy controls.

APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth.

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family designated APRIL (for a proliferation-inducing ligand). Although transcripts of APRIL are of low abundance in normal tissues, high levels of mRNA are detected in transformed cell lines, and in human cancers of colon, thyroid, and lymphoid tissues in vivo. The addition of recombinant APRIL to various tumor cells stimulates their proliferation. Moreover, APRIL-transfected NIH-3T3 cells show an increased rate of tumor growth in nude mice compared with the parental cell line. These findings suggest that APRIL may be implicated in the regulation of tumor cell growth.

Modelling changes in stable isotope compositions of minerals during net transfer reactions in a contact aureole: Wollastonite growth at the northern Hunter Mountain Batholith (Death Valley National Park, USA)

One of the world's largest wollastonite deposits was formed at the contact of the northern Hunter Mountain Batholith (California, USA) in Paleozoic sediments. Wollastonite occurs as zones of variable thickness surrounding layers or nodules of quartzite in limestones. A minimum formation temperature of 650 degrees C is estimated from isolated periclase-bearing lenses in that area. Contact metamorphism of siliceous carbonates has produced mineral assemblages that are consistent with heterogeneous, and partly limited infiltration of water-rich fluids, compatible with O-18/O-16 and C-13/C-12 isotopic patterns recorded in carbonates. Oxygen isotope compositions of wollastonites in the study area may also not require infiltration of large quantities of externally-derived fluids that were out of equilibrium with the rocks. 8180 values of wollastonite are high (14.8 parts per thousand to 25.0 parts per thousand; median: 19.7 parts per thousand) and close to those of the host limestone (19.7 parts per thousand to 28 parts per thousand; median: 24.9 parts per thousand) and quartz (18.0 parts per thousand. to 29.1 parts per thousand; median: 22.6 parts per thousand). Isotopic disequilibrium exists at quartz/wollastonite and wollastonite/calcite boundaries. Therefore, classical batch/Rayleigh fractionation models based on reactant and product equilibrium are not applicable to the wollastonite rims. An approach that relies on local instantaneous mass balance for the reactants, based on the wollastonite-forming reaction is suggested as an alternative way to model wollastonite reaction rims. This model reproduces many of the measured delta O-18 values of wollastonite reaction rims of the current study to within +/- 1 parts per thousand, even though the wollastonite compositions vary by almost 10 parts per thousand. (C) 2011 Elsevier B.V. All rights reserved.

Litterfall and mineral return in two cork-oak forests in northeast spain

Seasonal trends in littertall and potential mineral return were studied in two cork-oak forest sites in the northeastern Iberian peninsula. The estimated average litter production was 3.9.M- gy.e1ahar for one site and 4.6 .M- gy.e1ahar for the other; these figures are similar to those reported for holm-oak (Quercus ilex) forests in the same area. Seasonal litterfall patterns were typical of Mediterranean forest ecosystems. Leaves accounted for 46 to 78% of the total dry matter. Their annual weighted-average mineral composition was low in macronutrients (N 8-9; K 4-5; Mg 0.8-1.3; Ca 9-10 and P 0.4-1 m-)g.1g and relatively high in micronutrients such as Mn (2-2.2 m-)g.1g or Fe (0.3-0.4 m)-g..1g Minimum N and P concentrations were found during the growth period. Estimates of potential mineral return for an annual cycle were N 38-52, P 2.1-5.2, K 20-28, Ca 44-53 and Mg 5.4-5.0 k-,g.1ha depending on the site biomass and fertility

Circulating insulin-like growth factor-I in pregnancy and maternal risk of breast cancer.

BACKGROUND: Elevated serum concentrations of insulin-like growth factor (IGF)-1 have been associated with increased risk of breast cancer. Previously, we reported a similar association in samples obtained during pregnancy. The current study was conducted to further characterize the association of IGF-1 during pregnancy with maternal breast cancer risk. METHODS: A case-control study was nested within the Finnish Maternity Cohort. The study was limited to primiparous women less than 40 years of age, who donated blood samples during early (median, 12 weeks) pregnancy and delivered a single child at term. Seven hundred and nineteen women with invasive breast cancer were eligible. Two controls (n = 1,434) were matched to each case on age and date at blood donation. Serum IGF-1 concentration was measured using an Immulite 2000 analyzer. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).RESULTS: No significant associations were observed between serum IGF-1 concentrations and breast cancer risk in both the overall analysis (OR 1.08 (95% CI 0.80-1.47) and in analyses stratified by histological subtype, lag-time to cancer diagnosis, age at pregnancy or age at diagnosis.CONCLUSIONS: There was no association between IGF-1 and maternal breast cancer risk during early pregnancy in this large nested case-control study.Impact:Serum IGF-1 concentrations during early pregnancy may not be related to maternal risk of breast cancer.

Light-regulated plant growth and development.

Plants are sessile and photo-autotrophic; their entire life cycle is thus strongly influenced by the ever-changing light environment. In order to sense and respond to those fluctuating conditions higher plants possess several families of photoreceptors that can monitor light from UV-B to the near infrared (far-red). The molecular nature of UV-B sensors remains unknown, red (R) and far-red (FR) light is sensed by the phytochromes (phyA-phyE in Arabidopsis) while three classes of UV-A/blue photoreceptors have been identified: cryptochromes, phototropins, and members of the Zeitlupe family (cry1, cry2, phot1, phot2, ZTL, FKF1, and LKP2 in Arabidopsis). Functional specialization within photoreceptor families gave rise to members optimized for a wide range of light intensities. Genetic and photobiological studies performed in Arabidopsis have shown that these light sensors mediate numerous adaptive responses (e.g., phototropism and shade avoidance) and developmental transitions (e.g., germination and flowering). Some physiological responses are specifically triggered by a single photoreceptor but in many cases multiple light sensors ensure a coordinated response. Recent studies also provide examples of crosstalk between the responses of Arabidopsis to different external factors, in particular among light, temperature, and pathogens. Although the different photoreceptors are unrelated in structure, in many cases they trigger similar signaling mechanisms including light-regulated protein-protein interactions or light-regulated stability of several transcription factors. The breath and complexity of this topic forced us to concentrate on specific aspects of photomorphogenesis and we point the readers to recent reviews for some aspects of light-mediated signaling (e.g., transition to flowering).

Seasonal changes of whole root system conductance by a drought-tolerant grape root system

The role of root systems in drought tolerance is a subject of very limited information compared with above-ground responses. Adjustments to the ability of roots to supply water relative to shoot transpiration demand is proposed as a major means for woody perennial plants to tolerate drought, and is often expressed as changes in the ratios of leaf to root area (AL:AR). Seasonal root proliferation in a directed manner could increase the water supply function of roots independent of total root area (AR) and represents a mechanism whereby water supply to demand could be increased. To address this issue, seasonal root proliferation, stomatal conductance (gs) and whole root system hydraulic conductance (kr) were investigated for a drought-tolerant grape root system (Vitis berlandieri×V. rupestris cv. 1103P) and a non-drought-tolerant root system (Vitis riparia×V. rupestris cv. 101-14Mgt), upon which had been grafted the same drought-sensitive clone of Vitis vinifera cv. Merlot. Leaf water potentials (ψL) for Merlot grafted onto the 1103P root system (–0.91±0.02 MPa) were +0.15 MPa higher than Merlot on 101-14Mgt (–1.06±0.03 MPa) during spring, but dropped by approximately –0.4 MPa from spring to autumn, and were significantly lower by –0.15 MPa (–1.43±0.02 MPa) than for Merlot on 101-14Mgt (at –1.28±0.02 MPa). Surprisingly, gs of Merlot on the drought-tolerant root system (1103P) was less down-regulated and canopies maintained evaporative fluxes ranging from 35–20 mmol vine−1 s−1 during the diurnal peak from spring to autumn, respectively, three times greater than those measured for Merlot on the drought-sensitive rootstock 101-14Mgt. The drought-tolerant root system grew more roots at depth during the warm summer dry period, and the whole root system conductance (kr) increased from 0.004 to 0.009 kg MPa−1 s−1 during that same time period. The changes in kr could not be explained by xylem anatomy or conductivity changes of individual root segments. Thus, the manner in which drought tolerance was conveyed to the drought-sensitive clone appeared to arise from deep root proliferation during the hottest and driest part of the season, rather than through changes in xylem structure, xylem density or stomatal regulation. This information can be useful to growers on a site-specific basis in selecting rootstocks for grape clonal material (scions) grafted to them.

Impact of Anti-T-Cell Therapy in the Immunogenicity of Seasonal Influenza Vaccine in Kidney Transplant Recipients.

BACKGROUND: The influence of anti-T-cell therapy in the immunogenicity of the influenza vaccine in kidney transplant recipients remains unclear. METHODS: During the 2010 to 2011 influenza season, we evaluated the immune response to the inactivated trivalent influenza vaccine in kidney transplant recipients having received Thymoglobulin or basiliximab as induction therapy. A hemagglutination inhibition assay was used to assess the immunogenicity of the vaccine. The primary outcome was geometric mean titers of hemagglutination inhibition after influenza vaccination. RESULTS: Sixty patients (Thymoglobulin n=22 and basiliximab n=38) were included. Patients in the Thymoglobulin group were older (P=0.16), showed higher creatinine levels (P=0.16) and had more frequently received a previous transplant (P=0.02). There were no significant differences in geometric mean titers for any of the three viral strains between groups (P=0.69 for H1N1, P=0.56 for H3N2, and P=0.7 for B strain). Seroconversion to at least one viral strain was seen in 15 (68%) of 22 patients in the Thymoglobulin group and 28 (73%) of 38 in the basiliximab group (P=0.77). In patients vaccinated during the first year after receiving anti-T-cell therapy (n=25), there was a trend toward lower vaccine responses in the Thymoglobulin group. Patients who received Thymoglobulin showed lower CD4 cell counts and lower levels of IgM, at an average of 16.2 months after transplantation. A multivariate analysis showed that only the absence of mycophenolate was associated with a better vaccine response (odds ratio=9.47; 95% confidence interval, 1.03-86.9; P=0.047). CONCLUSION: No significant differences were seen in immunogenicity of the influenza vaccine in kidney transplant recipients having received either Thymoglobulin or basiliximab.

Relatedness among arbuscular mycorrhizal fungi drives plant growth and intraspecific fungal coexistence.

Arbuscular mycorrhizal fungi (AMF) form symbioses with most plant species. They are ecologically important determinants of plant growth and diversity. Considerable genetic variation occurs in AMF populations. Thus, plants are exposed to AMF of varying relatedness to each other. Very little is known about either the effects of coexisting AMF on plant growth or which factors influence intraspecific AMF coexistence within roots. No studies have addressed whether the genetics of coexisting AMF, and more specifically their relatedness, influences plant growth and AMF coexistence. Relatedness is expected to influence coexistence between individuals, and it has been suggested that decreasing ability of symbionts to coexist can have negative effects on the growth of the host. We tested the effect of a gradient of AMF genetic relatedness on the growth of two plant species. Increasing relatedness between AMFs lead to markedly greater plant growth (27% biomass increase with closely related compared to distantly related AMF). In one plant species, closely related AMF coexisted in fairly equal proportions but decreasing relatedness lead to a very strong disequilibrium between AMF in roots, indicating much stronger competition. Given the strength of the effects with such a shallow relatedness gradient and the fact that in the field plants are exposed to a steeper gradient, we consider that AMF relatedness can have a strong role in plant growth and the ability of AMF to coexist. We conclude that AMF relatedness is a driver of plant growth and that relatedness is also a strong driver of intraspecific coexistence of these ecologically important symbionts.

Microstructural, chemical and textural records during growth of snowball garnet

The growth history of two populations of snowball garnet from the Lukmanier Pass area (central Swiss Alps) was examined through a detailed analysis of three-dimensional geometry, chemical zoning and crystallographic orientation. The first population, collected in the hinge of a chevron-type fold, shows an apparent rotation of 360 degrees. The first 270 degrees are characterized by spiral-shaped inclusion trails, gradual and concentric Mn zoning and a single crystallographic orientation, whereas in the last 90 degrees, crenulated inclusion trails and secondary Mn maxima centred on distinct crystallographic garnet domains are observed. Microstructural, geochemical and textural data indicate a radical change in growth regime between the two growth sequences. In the first 270 degrees, growth occurred under rotational non-coaxial flow, whereas in the last 90 degrees, garnet grew under a non-rotational shortening regime. The second population, collected in the limb of the same chevron-type fold structure, is characterized by a spiral geometry that does not exceed 270 degrees of apparent rotation. These garnet microstructures do not record any evidence for a modification of the stress field during garnet growth. Concentric Mn zoning as well as a single crystallographic orientation are observed for the entire spiral. Electron backscatter diffraction data indicate that nearly all central domains in the snowball garnet are characterized by one [001] axis oriented (sub-)parallel to the symmetry axis and by another [001] axis oriented (sub-)parallel to the orientation of the internal foliation. These features suggest that the crystallographic orientation across the garnet spiral is not random and that a relation exists among the symmetry axis, the internal foliation and the crystallographic orientation.

BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth.

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M-stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center-like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.

Support for Seasonal Influenza Vaccination Requirements among US Healthcare Personnel.

Objective. To measure support for seasonal influenza vaccination requirements among US healthcare personnel (HCP) and its associations with attitudes regarding influenza and influenza vaccination and self-reported coverage by existing vaccination requirements. Design. Between June 1 and June 30, 2010, we surveyed a sample of US HCP ([Formula: see text]) recruited using an existing probability-based online research panel of participants representing the US general population as a sampling frame. Setting. General community. Participants. Eligible HCP who (1) reported having worked as medical doctors, health technologists, healthcare support staff, or other health practitioners or who (2) reported having worked in hospitals, ambulatory care facilities, long-term care facilities, or other health-related settings. Methods. We analyzed support for seasonal influenza vaccination requirements for HCP using proportion estimation and multivariable probit models. Results. A total of 57.4% (95% confidence interval, 53.3%-61.5%) of US HCP agreed that HCP should be required to be vaccinated for seasonal influenza. Support for mandatory vaccination was statistically significantly higher among HCP who were subject to employer-based influenza vaccination requirements, who considered influenza to be a serious disease, and who agreed that influenza vaccine was safe and effective. Conclusions. A majority of HCP support influenza vaccination requirements. Moreover, providing HCP with information about the safety of influenza vaccination and communicating that immunization of HCP is a patient safety issue may be important for generating staff support for influenza vaccination requirements.

Epidermal growth factor (EGF) stimulation of cultured brain cells. I. Enhancement of the developmental increase in glial enzymatic activity.

Serum-free aggregating cell cultures of fetal rat telencephalon grown in the presence of 3 ng/ml (5 X 10(-10) M) epidermal growth factor (EGF) until day 12 showed 2- to 3-fold increased activities in the two glial enzymes, glutamine synthetase (GLU-S) and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase). This effect was concentration-dependent, with maximal stimulation in cultures treated daily with 3 ng/ml EGF. Addition of EGF during the first 10 culture days was sufficient to produce a maximal stimulation of both GLU-S and CNPase on day 19, whereas treatments starting on day 12 were ineffective. The stimulation of GLU-S preceded that of CNPase. The EGF-induced increase in GLU-S activity was not directly dependent on the presence of insulin, triiodothyronine, or hydrocortisone in the medium, whereas insulin was required for the stimulation of CNPase. A single dose of 5 ng/ml EGF on day 2 caused a slight but significant decrease in DNA synthesis after day 6. The present results indicate that in serum-free aggregating cell cultures of fetal rat telencephalon EGF partially inhibits DNA synthesis, and stimulates an early step in glial differentiation.