Reduced plate motion controlled timing of Early Jurassic Karoo-Ferrar large igneous province volcanism.

Past large igneous province (LIP) emplacement is commonly associated with mantle plume upwelling and led to major carbon emissions. One of Earth's largest past environmental perturbations, the Toarcian oceanic anoxic event (T-OAE; ~183 Ma), has been linked to Karoo-Ferrar LIP emplacement. However, the role of mantle plumes in controlling the onset and timing of LIP magmatism is poorly understood.

Leishmania donovani infection suppresses Allograft Inflammatory Factor-1 in monocytes and macrophages to inhibit inflammatory responses.

Macrophages and monocytes are important for clearance of Leishmania infections. However, immune evasion tactics employed by the parasite results in suppressed inflammatory responses, marked by deficient macrophage functions and increased accumulation of monocytes. This results in an ineffective ability to clear parasite loads.

Allograft inflammatory factor-1 in myeloid cells drives autoimmunity in type 1 diabetes.

Allograft inflammatory factor-1 (AIF1) is a calcium-responsive cytoplasmic scaffold protein that directs hematopoiesis and immune responses within dendritic cells (DC) and macrophages. Although the role of AIF1 in transplant rejection and rheumatoid arthritis has been explored, little is known about its role in type 1 diabetes. Here, we show that in vivo silencing of AIF1 in NOD mice restrained infiltration of immune cells into the pancreas and inhibited diabetes incidence.

Environmental variables and errors in the preparation and administration of medicines.

Objective: to identify the relationship between environmental factors and errors in the preparation and administration of antibacterial.

Method: an observational, cross-sectional study conducted between August and December, 2014 in two clinical units. The sample consisted of 265 doses of medication, observed in different shifts that through a form had the environmental conditions of noise, illumination, humidity, temperature and physical space measured in the preparation and administration stages.

sCD163 levels as a biomarker of disease severity in leprosy and visceral leishmaniasis.

Background: CD163, receptor for the haptoglobin-hemoglobin complex, is expressed on monocytes/macrophages and neutrophils. A soluble form of CD163 (sCD163) has been associated with the M2 macrophage phenotype, and M2 macrophages have been shown to down-modulate inflammatory responses. In particular, previous studies have shown that M2 is closely associated with the most severe clinical presentation of leprosy (i.

B cells Can Modulate the CD8 Memory T Cell after DNA Vaccination Against Experimental Tuberculosis.

Background: Although B cells are important as antigen presenting cells (APC) during the immune response, their role in DNA vaccination models is unknown.

Methods: In this study in vitro and in vivo experiments were performed to evaluate the ability of B cells to protect mice against Mycobacterium tuberculosis challenge.

Results: In vitro and in vivo studies showed that B cells efficiently present antigens after naked plasmid pcDNA3 encoding M.

Tumorigenic activity and therapeutic inhibition of Rheb GTPase.

The AKT-mTOR pathway harbors several known and putative oncogenes and tumor suppressors. In a phenotypic screen for lymphomagenesis, we tested candidate genes acting upstream of and downstream from mTOR in vivo. We find that Rheb, a proximal activator of mTORC1, can produce rapid development of aggressive and drug-resistant lymphomas.

Genetic analysis of Dengue 3 virus subtype III 5' and 3' non-coding regions.

The emergence of dengue hemorrhagic fever in Sri Lanka in 1989 correlated with the appearance of a genetic variant of Dengue 3 virus (DENV-3) subtype III (group B), closely related to the endemic group A variant. We studied the 5' and 3' non-coding regions (NCRs) of 15 DENV-3 subtype III isolates from Sri Lanka, Nicaragua and Martinique and found variability in the 3' NCRs. This included an 11-nucleotide insertion common to all isolates examined and two nucleotide differences that segregated viruses geographically into an American and a Sri Lankan group.

MNK, EIF4E and targeting translation for therapy.

Deregulation of protein translation is a common event in cancer and occurs frequently as a result of mutational activation of the AKT signaling pathway. We had previously reported the in vivo oncogenic activity of the translation initiation factor eIF4E, which acts downstream AKT and mTOR. We now identified an absolute requirement for Ser209 phosphorylation by the MNK1/2 kinases for eIF4E's oncogenic action.

Dissecting eIF4E action in tumorigenesis.

Genetically engineered mouse models are powerful tools for studying cancer genes and validating targets for cancer therapy. We previously used a mouse lymphoma model to demonstrate that the translation initiation factor eIF4E is a potent oncogene in vivo. Using the same model, we now show that the oncogenic activity of eIF4E correlates with its ability to activate translation and become phosphorylated on Ser 209.

The Arf tumor suppressor regulates platelet-derived growth factor receptor beta signaling: a new view through the eyes of Arf(-/-) mice.

Arf is a key mammalian tumor suppressor gene known to be activated in response to aberrant mitogenic signals leading to both p53-dependent and -independent effects. We recently uncovered a new and somewhat unexpected function for mouse Arf as a regulator of mural cell accumulation within an ocular vascular bed destined to regress in the postnatal period. We found that the Arf gene product, p19(Arf), blocks mural cell proliferation driven by Platelet-derived growth factor receptor beta (Pdgfrbeta) in the developing vitreous.

Arf-dependent regulation of Pdgf signaling in perivascular cells in the developing mouse eye.

We have established that the Arf tumor suppressor gene regulates mural cell biology in the hyaloid vascular system (HVS) of the developing eye. In the absence of Arf, perivascular cells accumulate within the HVS and prevent its involution. We now demonstrate that mural cell accumulation evident at embryonic day (E) 13.

Comparative analysis of amplified and nonamplified RNA for hybridization in cDNA microarray.

Limiting amounts of RNA is a major issue in cDNA microarray, especially when one is dealing with fresh tissue samples. Here we describe a protocol based on template switch and T7 amplification that led to efficient and linear amplification of 1300x. Using a glass-array containing 368 genes printed in three or six replicas covering a wide range of expression levels and ratios, we determined quality and reproducibility of the data obtained from one nonamplified and two independently amplified RNAs (aRNA) derived from normal and tumor samples using replicas with dye exchange (dye-swap measurements).

cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells.

To investigate changes in gene expression associated with ERBB2, expression profiling of immortalized human mammary luminal epithelial cells and variants expressing a moderate and high level of ERBB2 has been carried out using cDNA microarrays corresponding to approximately 6000 unique genes/ESTs. A total of 61 significantly up- or downregulated (2.0-fold) genes were identified and further validated by RT-PCR analysis as well as microarray comparisons with a spontaneously ERBB2- overexpressing breast cancer cell line and ERBB2-positive primary breast tumors.

Differentially expressed genes in gastric tumors identified by cDNA array.

Using cDNA fragments from the FAPESP/lICR Cancer Genome Project, we constructed a cDNA array having 4512 elements and determined gene expression in six normal and six tumor gastric tissues. Using t-statistics, we identified 80 cDNAs whose expression in normal and tumor samples differed more than 3.5 sample standard deviations.