SHRIMP ion probe zircon geochronology and Sr and Nd isotope geochemistry for southern Longwood Range and Bluff Peninsula intrusive rocks of Southland, New Zealand

Permian–Jurassic ultramafic to felsic intrusive complexes at Bluff Peninsula and in the southern Longwood Range along the Southland coast represent a series of intraoceanic magmatic arcs with ages spanning a time interval of 110 m.y. New SHRIMP U-Pb zircon data for a quartz diorite from the Flat Hill complex, Bluff Peninsula, yield an age of 259 ± 4 Ma, consistent with other geochronological and paleontological evidence confirming a Late Permian age. The new data are consistent with an age of c. 260 Ma for the intrusive rocks of the Brook Street Terrane. SHRIMP U-Pb zircon ages for the southern Longwood Range confirm that intrusions become progressively younger from east to west across the complex. A gabbro at Oraka Point (eastern end of coastal section) has an age of 245 ± 4 Ma and shows virtually no evidence of zircon inheritance. The age is significantly different from that of the Brook Street Terrane intrusives. Zircon ages from the western parts of the section are younger and more varied (203–227 Ma), indicating more complex magmatic histories. A leucogabbro dike from Pahia Point gives the youngest emplacement age of 142 Ma, which is similar to published U-Pb zircon ages for the Anglem Complex and Paterson Group on Stewart Island

A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt–TSC2-mTOR signaling

Nanoparticles are now emerging as a novel class of autophagy activators. Functionalized single-walled carbon nanotubes (f-SWCNTs) are valuable nanomaterials in many industries. This article is designed to assess the autophagic response for f-SWCNTs exposure in vitro and in vivo. A few types of f-SWCNTs were screened in human lung adenocarcinoma A549 cells for the autophagic response and related pathways in vitro. Formation of autophagosomes and LC3-II upregulation were confirmed on the basis of electron microscopy and LC3 western blotting for COOH-CNT, but not for PABS-CNT and PEG-CNT. MTT assay showed marked increase in cell viability, when COOH-CNT was added to cells in the presence of autophagy inhibitor 3MA, ATG6 or TSC2 siRNA. Consistent with the involvement of the Akt–TSC1/2–mTOR pathway, the phosphorylation levels of mTOR, mTOR's substrate S6 and Akt were shown significantly decreased in A549 cells on treatment with COOH-CNT using western blotting. What's more, autophagy inhibitor 3MA significantly reduced the lung edema in vivo. In a word, COOH-CNT induced autophagic cell death in A549 cells through the AKT–TSC2–mTOR pathway and caused acute lung injury in vivo. Inhibition of autophagy significantly reduced COOH-CNT-induced autophagic cell death and ameliorated acute lung injury in mice, suggesting a potential remedy to address the growing concerns on the safety of nanomaterials

Limited Vegetation Development on a Created Salt Marsh Associated with Over-Consolidated Sediments and Lack of Topographic Heterogeneity

Restored salt marshes frequently lack the full range of plant communities present on reference marshes, with upper marsh species underrepresented. This often results from sites being too low in the tidal frame and/or poorly drained with anoxic sediments. A managed coastal realignment scheme at Abbotts Hall, Essex, UK, has oxic sediments at elevations at which upper marsh communities would be expected. But 7 years after flooding, it continued to be dominated by pioneer communities, with substantial proportions of bare ground, so other factors must hinder vegetation development at these elevations. The poorly vegetated areas had high sediment shear strength, low water and organic carbon content and very flat topography. These characteristics occur frequently on the upper parts of created marshes. Experimental work is required to establish causal links with the ecological differences, but other studies have also reported that reduced plant β-diversity and lower usage by fish are associated with topographic uniformity. Uniformity also leads to very different visual appearance from natural marshes. On the upper intertidal, sediment deposition rate are slow, water velocities are low and erosive forces are weak. So, topographic heterogeneity cannot develop naturally, even if creeks have been excavated. Without active management, these conditions will persist indefinitely

Induction of protein citrullination and auto-antibodies production in murine exposed to nickel

Abstract Citrullination, or the post-translational deimination of polypeptide-bound arginine, is involved in several pathological processes in the body, including autoimmunity and tumorigenesis. Recent studies have shown that nanomaterials can trigger protein citrullination, which might constitute a common pathogenic link to disease development. Here we demonstrated auto-antibody production in serum of nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels were found to be elevated in nanomaterials -treated cell lines as well as in the spleen, kidneys and lymph nodes of mice, suggesting a systemic response to nanomaterials injection, and validated in human pleural and pericardial malignant mesothelioma (MM) samples. The observed systemic responses in mice exposed to nanomaterials support the evidence linking exposure to environmental factors with the development of autoimmunity responses and reinforces the need for comprehensive safety screening of nanomaterials. Furthermore, these nanomaterials induce pathological processes that mimic those observed in Pleural MM, and therefore require further investigations into their carcinogenicity

Differential In Vitro Effects of Intravenous versus Oral Formulations of Silibinin on the HCV Life Cycle and Inflammation

Silymarin prevents liver disease in many experimental rodent models, and is the most popular botanical medicine consumed by patients with hepatitis C. Silibinin is a major component of silymarin, consisting of the flavonolignans silybin A and silybin B, which are insoluble in aqueous solution. A chemically modified and soluble version of silibinin, SIL, has been shown to potently reduce hepatitis C virus (HCV) RNA levels in vivo when administered intravenously. Silymarin and silibinin inhibit HCV infection in cell culture by targeting multiple steps in the virus lifecycle. We tested the hepatoprotective profiles of SIL and silibinin in assays that measure antiviral and anti-inflammatory functions. Both mixtures inhibited fusion of HCV pseudoparticles (HCVpp) with fluorescent liposomes in a dose-dependent fashion. SIL inhibited 5 clinical genotype 1b isolates of NS5B RNA dependent RNA polymerase (RdRp) activity better than silibinin, with IC50 values of 40–85 µM. The enhanced activity of SIL may have been in part due to inhibition of NS5B binding to RNA templates. However, inhibition of the RdRps by both mixtures plateaued at 43–73%, suggesting that the products are poor overall inhibitors of RdRp. Silibinin did not inhibit HCV replication in subgenomic genotype 1b or 2a replicon cell lines, but it did inhibit JFH-1 infection. In contrast, SIL inhibited 1b but not 2a subgenomic replicons and also inhibited JFH-1 infection. Both mixtures inhibited production of progeny virus particles. Silibinin but not SIL inhibited NF-κB- and IFN-B-dependent transcription in Huh7 cells. However, both mixtures inhibited T cell proliferation to similar degrees. These data underscore the differences and similarities between the intravenous and oral formulations of silibinin, which could influence the clinical effects of this mixture on patients with chronic liver diseases

Azacytidine and Decitabine Induce Gene-Specific and Non-Random DNA Demethylation in Human Cancer Cell Lines

The DNA methyltransferase inhibitors azacytidine and decitabine represent archetypal drugs for epigenetic cancer therapy. To characterize the demethylating activity of azacytidine and decitabine we treated colon cancer and leukemic cells with both drugs and used array-based DNA methylation analysis of more than 14,000 gene promoters. Additionally, drug-induced demethylation was compared to methylation patterns of isogenic colon cancer cells lacking both DNA methyltransferase 1 (DNMT1) and DNMT3B. We show that drug-induced demethylation patterns are highly specific, non-random and reproducible, indicating targeted remethylation of specific loci after replication. Correspondingly, we found that CG dinucleotides within CG islands became preferentially remethylated, indicating a role for DNA sequence context. We also identified a subset of genes that were never demethylated by drug treatment, either in colon cancer or in leukemic cell lines. These demethylation-resistant genes were enriched for Polycomb Repressive Complex 2 components in embryonic stem cells and for transcription factor binding motifs not present in demethylated genes. Our results provide detailed insights into the DNA methylation patterns induced by azacytidine and decitabine and suggest the involvement of complex regulatory mechanisms in drug-induced DNA demethylation

Psychopathic traits and offender characteristics – a nationwide consecutive sample of homicidal male adolescents

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to evaluate psychopathy-like personality traits in a nationwide consecutive sample of adolescent male homicide offenders and to compare the findings with those of a randomly sampled adult male homicide offender group. A further aim was to investigate associations between psychopathic traits and offender and offence characteristics in adolescent homicides.</p> <p>Methods</p> <p>Forensic psychiatric examination reports and crime reports of all 15 to19- year- old male Finnish offenders who had been subjected to a forensic psychiatric examination and convicted for a homicide during 1995–2004 were collected (n = 57). A random sample of 57 adult male homicide offenders was selected as a comparison group. Offence and offender characteristics were collected from the files and a file-based assessment of psychopathic traits was performed using the Hare Psychopathy Checklist-Revised (PCL-R) by trained raters.</p> <p>Results</p> <p>No significant differences existed between the adolescents and adults in PCL-R total scores, factor 2 (social deviance) scores, or in facets 3 (lifestyle) and 4 (antisocial). Adults scored significantly higher on factor 1 (interpersonal/affective) and facets 1 (interpersonal) and 2 (affective). The adolescent group was divided into two subgroups according to PCL-R total scores. One in five homicidal male adolescents met criteria for psychopathic personality using a PCL-R total score of 26 or higher. These boys significantly more often had a crime history before the index homicide, more frequently used excessive violence during the index homicide, more rarely lived with both parents until 16 years of age, had more institutional or foster home placements in childhood, had more school difficulties, more often had received special education, and, more often had contact with mental health services prior to age 18 years than boys scoring low on the PCL-R. They also more often had parental criminal history as well as homicide history of parents or near relatives than the group scoring low on the PCL-R.</p> <p>Conclusion</p> <p>Homicidal boys behaved as antisocially as the homicidal adults. The adults, however, showed more both affective and interpersonal features of psychopathy. Homicidal adolescents with psychopathy-like personality character form a special subgroup among other homicidal youngsters. Recognizing their characteristics, especially in life course development, would facilitate effective prevention and intervention efforts.</p

Myosin IIA Modulates T Cell Receptor Transport and CasL Phosphorylation during Early Immunological Synapse Formation

Activation of T cell receptor (TCR) by antigens occurs in concert with an elaborate multi-scale spatial reorganization of proteins at the immunological synapse, the junction between a T cell and an antigen-presenting cell (APC). The directed movement of molecules, which intrinsically requires physical forces, is known to modulate biochemical signaling. It remains unclear, however, if mechanical forces exert any direct influence on the signaling cascades. We use T cells from AND transgenic mice expressing TCRs specific to the moth cytochrome c 88–103 peptide, and replace the APC with a synthetic supported lipid membrane. Through a series of high spatiotemporal molecular tracking studies in live T cells, we demonstrate that the molecular motor, non-muscle myosin IIA, transiently drives TCR transport during the first one to two minutes of immunological synapse formation. Myosin inhibition reduces calcium influx and colocalization of active ZAP-70 (zeta-chain associated protein kinase 70) with TCR, revealing an influence on signaling activity. More tellingly, its inhibition also significantly reduces phosphorylation of the mechanosensing protein CasL (Crk-associated substrate the lymphocyte type), raising the possibility of a direct mechanical mechanism of signal modulation involving CasL