Age and nature of 560–520 Ma calc-alkaline granitoids of Biarjmand, northeast Iran: insights into Cadomian arc magmatism in northern Gondwana

The Biarjmand granitoids and granitic gneisses in northeast Iran are part of the Torud–Biarjmand metamorphic complex, where previous zircon U–Pb geochronology show ages of ca. 554–530 Ma for orthogneissic rocks. Our new U–Pb zircon ages confirm a Cadomian age and show that the granitic gneiss is ~30 million years older (561.3 ± 4.7 Ma) than intruding granitoids(522.3 ± 4.2 Ma; 537.7 ± 4.7 Ma). Cadomian magmatism in Iran was part of an approximately 100-million-year-long episode of subduction-related arc and back-arc magmatism, which dominated the whole northern Gondwana margin, from Iberia to Turkey and Iran. Major REE and trace element data show that these granitoids have calc-alkaline signatures. Their zircon O (δ18O = 6.2–8.9‰) and Hf (–7.9 to +5.5; one point with εHf ~ –17.4) as well as bulk rock Nd isotopes (εNd(t)= –3 to –6.2) show that these magmas were generated via mixing of juvenile magmas with an older crust and/or melting of middle continental crust. Whole-rock Nd and zircon Hf model ages (1.3–1.6 Ga) suggest that this older continental crust was likely to have been Mesoproterozoic or even older. Our results, including variable zircon εHf(t) values, inheritance of old zircons and lack of evidence for juvenile Cadomian igneous rocks anywhere in Iran, suggest that the geotectonic setting during late Ediacaran and early Cambrian time was a continental magmatic arc rather than back-arc for the evolution of northeast Iran Cadomian igneous rocks.

Nego veio é um sofrer : uma etnografia da subalternidade e do subalterno numa irmandade do Rosário

The object of this work is a fellowship of São Sebastião e Nossa Senhora do Rosário in the city of Jardim do Seridó (RN), that is, a black catholic fellowship on the sertão potiguar. The devotion to Nossa Senhora do Rosário, in colonial Brazil, organizes itself through black catholic men as fellowships. They blossomed in Brazil until the abolition, getting support from the Catholic church, from owners of slaves and from the population in general − unlike others afro-Brazilian religious expression. Today, these fellowships remain active, against the sentimental pessimism of the folklore studies, and they also have a highlight position in the calendar of many cities in Brazil, and in particular in Seridó. The research s foothold is the apparent valorization of the fellowship by the local elite, attitude that hides asymmetric relationships between the group of negros do Rosário and the local authorities, having as its consequence that the members occupy a subaltern position inside their own fellowship. This subalternity take place, mainly, in the public area, where the negros do Rosário cannot represent themselves neither political nor discursively. To discuss this idea, it s done a brief historical of these catholic institutions as well as a description of the relationship between the negros do Rosário and the elites of the city. Then, the phenomenon is analyzed as folklore and/or religion , under the perspective of many agents that participate in this process. In other moment, it is going to be presented how the group formulates their own representation of the history, of the devotional forms and of their own political-religious experiences. In this sense, an ethnography of the subalternity is understood as an analysis of the process that leads the negros do Rosário to become a subaltern group. It s also outlined the perception that the group has of its own position, through an ethnography essay of the subaltern subject. The research, focused in the group of Rosário, was done between August 2010 and January 2012 and includes other agents (like treasurers, priests and intellectuals). Besides that, as a methodological complement, there are documental research, photography, as well as shoots of the party days and public presentation

The role of glucocorticoids in naturally fasting grey seal (Halichoerus grypus) pups: dexamethasone stimulates mass loss and protein utilisation, but not departure from the colony

Seals must manage their energy reserves carefully while they fast on land to ensure that they go to sea with sufficient fuel to sustain them until they find food. Glucocorticoids (GCs) have been implicated in the control of fuel metabolism and termination of fasting in pinnipeds. Here we tested the hypothesis that dexamethasone, an artificial GC, increases fat and protein catabolism, and induces departure from the breeding colony in wild, fasting grey seal pups. A single intramuscular dose of dexamethasone completely suppressed cortisol production for 24–72 h, demonstrating activation of GC receptors. In experiment 1, we compared the effects of a single dose of dexamethasone or saline administered 10 days after weaning on fasting mass and body composition changes, cortisol, blood urea nitrogen (BUN) and glucose levels, and timing of departure from the colony. In experiment 2, we investigated the effects of dexamethasone on short-term (5 days) changes in mass loss, body composition and BUN levels. In experiment 1, dexamethasone induced a short-lived increase in mass loss, but there was no difference in timing of departure between dexamethasone- and saline-treated pups (N=10). In experiment 2, dexamethasone increased protein and water loss and prevented a decrease in BUN levels (N=11). Our data suggest changes in cortisol contribute to regulation of protein catabolism in fasting seal pups, irrespective of the sex of the animal, but do not terminate fasting. By affecting the rate of protein depletion, lasting changes in cortisol levels could influence the amount of time seal pups have to find food, and thus may have important consequences for their survival.

Espirito de catimbo: a moral magico-religiosa da jurema

This participative research interested in the social praxis attempts to understand the moral principles that set the magic rituals and the places of worship of three jurema centers of the potiguar region of Canguaretama. Among other inner particularly aspects of each focused catimbó-jurema center, it is being discussed the collective standards involved in the reliance and fellowship values assumed in the private magical gatherings by the juremeiras leaders and their partners, in contrast to the prestige seeking and the individualism that influence both the symbolic competitions and the witchcraft works that link these agents to the broader catimbozeiro universe of this region. Finally, the moral practices which make part of the juremeiro left-right dualism are investigated based on the understanding that the referred native pantheonic-ritual dichotomy does not necessarily express two moralities substantially adversed in terms of benefits or harms, but a series of moral actions subject to the specular logic of the tit-for tat. Thus, this research seeks to prove that this moral structure of symbolic reciprocity, as well as the witchcraft centrality in the catimbozeiro world, finds a certain causal link in a world view which guiding principle is the ontological evil of the catholic cosmology

Effects of handling regime and sex on changes in cortisol, thyroid hormones and body mass in fasting grey seal pups

Survival of seal pups may be affected by their ability to respond appropriately to stress. Chronic stress can adversely affect secretion of cortisol and thyroid hormones, which contribute to the control of fuel utilisation. Repeated handling could disrupt the endocrine response to stress and/or negatively impact upon mass changes during fasting. Here we investigated the effects of handling regime on cortisol and thyroid hormone levels, and body mass changes, in fasting male and female grey seal pups (Halichoerus grypus). Females had higher thyroid hormone levels than males throughout fasting and showed a reduction in cortisol midway through the fast that was not seen in males. This may reflect sex-specific fuel allocation or development. Neither handling frequency nor cumulative contact time affected plasma cortisol or thyroid hormone levels, the rate of increase in cortisol over the first five minutes of physical contact or the pattern of mass loss during fasting in either sex. The endocrine response to stress and the control of energy balance in grey seal pups appear to be robust to repeated, short periods of handling. Our results suggest that routine handling should have no additional impact on these animals than general disturbance caused by researchers moving around the colony.

Functional analysis of the 5′ flanking region of the human G6PC3 gene: regulation of promoter activity by glucose, pyruvate, AMP kinase and the pentose phosphate pathway

G6PC3 is a widely expressed isoform of glucose-6-phosphatase, found in many foetal and adult tissues. Mutations in this gene cause developmental abnormalities and severe neutropenia due to abolition of glucose recycling between the cytoplasm and endoplasmic reticulum. Low G6PC3 expression as a result of promoter polymorphisms or dysregulation could produce similar outcomes. Here we investigated the regulation of human G6PC3 promoter activity. HeLa and H4IIE cells were transiently transfected with G6PC3 promoter coupled to the firefly luciferase gene, and promoter activity was measured by dual luciferase assay. Activity was highest in a 453 bp segment of the G6PC3 promoter, from − 455 to − 3 relative to the transcriptional start site. This promoter was unresponsive to glucostatic hormones. Its activity increased significantly between 1 and 5.5 mM glucose, and was not elevated further by glucose concentrations up to 25 mM. Pyruvate increased its activity, but β-hydroxybutyrate and sodium acetate did not. Promoter activity was reduced by inhibitors of hexokinase, glyceraldehyde phosphate dehydrogenase and the oxidative branch of the pentose phosphate pathway, but not by a transketolase inhibitor. Deletion of two adjacent Enhancer-boxes (− 274 to − 279 and − 299 to − 304) reduced promoter activity and abolished the glucose effect, suggesting they could function as a glucose response element. Deletion of an additional downstream 140 bp (− 140 to − 306) restored activity, but not the glucose response, suggesting the presence of repressor elements in this region. 5-Aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR) reduced promoter activity, showing dependence on AMP-kinase. Regulation of the G6PC3 promoter is thus radically different to that of the hepatic isoform, G6PC. It is sensitive to carbohydrate, but not to fatty acid metabolites, and at much lower physiological concentrations. Based on these findings, we speculate that reduced G6PC3 expression could occur during hypoglycemic episodes in vivo, which are common in utero and in the postnatal period. If such episodes lower G6PC3 expression they could place the foetus or infant at risk of impaired immune function and development, and this possibility requires further examination both in vitro and in vivo.

A LOFAR mini-survey for low-frequency radio emission from the nearest brown dwarfs

We have conducted a mini-survey for low-frequency radio emission from some of the closest brown dwarfs to the Sun with rapid rotation rates: SIMP J013656.5 +093347, WISEPC 150649.97+702736.0, and WISEPA J174124.26+255319.5.We have placed robust 3s upper limits on the flux density in the 111 – 169 MHz frequency range for these targets: WISE 1506: < 0:72 mJy; WISE 1741: < 0:87 mJy; SIMP 0136: < 0:66 mJy. At 8 hours of integration per target to achieve these limits, we find that systematic and detailed study of this class of object at LOFAR frequencies will require a substantial dedication of resources.

Do you what I say? people reconstruct the syntax of anomalous utterances

We frequently experience and successfully process anomalous utterances. Here we examine whether people do this by ‘correcting’ syntactic anomalies to yield well-formed representations. In two structural priming experiments, participants’ syntactic choices in picture description were influenced as strongly by previously comprehended anomalous (missing-verb) prime sentences as by well-formed prime sentences. Our results suggest that comprehenders can reconstruct the constituent structure of anomalous utterances – even when such utterances lack a major structural component such as the verb. These results also imply that structural alignment in dialogue is unaffected if one interlocutor produces anomalous utterances.

Soft tissue sarcoma: biology and therapeutic correlates

Soft tissue sarcomas (STS) comprise a heterogenenous group of greater than 50 malignancies of putative mesenchymal cell origin and as such they may arise in diverse tissue types in various anatomical locations throughout the whole body. Collectively they account for approximately 1% of all human malignancies yet have a spectrum of aggressive behaviours amongst their subtypes. They thus pose a particular challenge to manage and remain an under investigated group of cancers with no generally applicable new therapies in the past 40 years and an overall 5-year survival rate that remains stagnant at around 50%. From September 2000 to July 2006 I undertook a full time post-doctoral level research fellowship at the MD Anderson Cancer Center, Houston, Texas, USA in the department of Surgical Oncology to investigate the biology of soft tissue sarcoma and test novel anti- sarcoma adenovirus-based therapy in the preclinical nude rat model of isolated limb perfusion against human sarcoma xenografts. This work, in collaboration with colleagues as indicated herein, led to a number of publications in the scientific literature furthering our understanding of the malignant phenotype of sarcoma and reported preclinical studies with wild-type p53, in a replication deficient adenovirus vector, and oncolytic adenoviruses administered by isolated limb perfusion. Additional collaborative and pioneering preclinical studies reported the molecular imaging of sarcoma response to systemically delivered therapeutic phage RGD-4c AAVP. Doxorubicin chemotherapy is the single most active broadly applicable anti-sarcoma chemotherapeutic yet only has an approximate 30% overall response rate with additional breakthrough tumour progression and recurrence after initial chemo-responsiveness further problematic features in STS management. Doxorubicin is a substrate for the multi- drug resistance (mdr) gene product p-glycoprotein drug efflux pump and exerts its main mode of action by induction of DNA double-strand breaks during the S-phase of the cell cycle. Two papers in my thesis characterise different aspects of chemoresistance in sarcoma. The first shows that wild-type p53 suppresses Protein Kinase Calpha (PKCα) phosphorylation (and activation) of p-glycoprotein by transcriptional repression of PKCα through a Sp-1 transcription factor binding site in its -244/-234 promoter region. The second paper demonstrates that Rad51 (a central mediator of homologous recombination repair of double strand breaks) has elevated levels in sarcoma and particularly in the S- G2 phase of the cell cycle. Suppression of Rad51 with small interfering RNA in sarcoma cell culture led to doxorubicin chemosensitisation. Reintroduction of wild-type p53 into STS cell lines resulted in decreased Rad51 protein and mRNA expression via transcriptional repression of the Rad51 promoter through increased AP-2 binding. In light of poor response rates to chemotherapy, escape from local control portends a poor prognosis for patients with sarcoma. Two papers in my thesis characterise aspects of sarcoma angiogenesis, invasion and metastasis. Human sarcoma samples were found to have high levels of matrix metalloproteinase-9 (MMP-9) with expression levels that correlated with p53 mutational status. MMP-9 is known to degrade extracellular collagen, contribute to the control of the angiogenic switch necessary in primary tumour progression and facilitate invasion and metastasis. Reconstitution of wild-type p53 function led to decreased levels of MMP-9 protein and mRNA as well as zymography-assessed MMP-9 proteolytic activity and decreased tumour cell invasiveness. Reintroduction of wild-type p53 into human sarcoma xenografts in-vivo decreased tumour growth and MMP-9 protein expression. Wild-type p53 was found to suppress mmp-9 transcription via decreased binding of NF-κB to its -607/-595 mmp-9 promoter element. Studies on the role of the VEGF165 in sarcoma found that sarcoma cells stably transfected with VEGF165 formed more aggressive xenografted tumours with increased vascularity, growth rate, metastasis, and resistance to chemotherapy. Use of the anti-VEGFR2 antibody DC101 enhanced doxorubicin sensitivity at sub-conventional dosing, inhibited tumour growth, decreased development of metastases, and reduced tumour micro-vessel density while increasing the vessel maturation index. These effects were explained primarily through effects on endothelial cells (e.c.s), rather than the tumour cells per se, where DC101 induced e.c. sensitivity to doxorubicin and suppressed e.c. production of MMPs. The p53 tumour suppressor pathway is the most frequently mutated pathway in sarcoma. Recapitulation of wild-type p53 function in sarcoma exerts a number of anti-cancer outcomes such as growth arrest, resensitisation to chemotherapy, suppression of invasion, and attenuation of angiogenesis. Using a modified nude rat-human sarcoma xenograft model for isolated limb perfusion (ILP) delivery of wild-type p53 in a replication deficient adenovirus vector I showed that functionally competent wild-type p53 could be delivered to and detected in human leiomyosarcoma xenografts confirming preclinical feasibility - although not efficacious due to low transgene expression. Viral fibre modification to express the RGD tripeptide motif led to greater viral uptake by sarcoma cells in vitro (transductional targeting) and changing the transgene promoter to a response element active in cells with active telomerase expression restricted the transgene expression to the tumour intracellular environment (transcriptional targeting). Delivery of the fibre-modified, selectively replication proficient oncolytic adenovirus Ad.hTC.GFP/ E1a.RGD by ILP demonstrated a more robust, and tumour-restricted, transgene expression with evidence of anti-sarcoma effect confirmed microscopically. Collaborative studies using the fibre modified phage RGD-4C AAVP confirmed that systemic delivery specifically, efficiently, and repeatedly targets human sarcoma xenografts, binds to αv integrins in tumours, and demonstrates a durable, though heterogeneous, transgene expression of 1-4 weeks. Incorporation of the Herpes Simplex Virus thymidine kinase (HSVtk) transgene into RGD-4C AAVP permitted CT-PET spatial and temporal molecular imaging in vivo of transgene expression and allowed quantification of tumour metabolic activity both before and after interval administration of a systemic cytotoxic with predictable and measurable response to treatment before becoming apparent clinically. These papers further the medical and scientific community’s understanding of the biology of soft tissue sarcoma and report preclinical studies with novel and promising anti- sarcoma therapeutics.

Substance use disorder comorbidity with schizophrenia in families of Mexican and Central American Ancestry

artículo -- Universidad de Costa Rica. Centro Investigación en Biología Molecular y Celular, 2010. Este documento es privado debido a limitaciones de derechos de autor.

dachshund Potentiates Hedgehog Signaling during Drosophila Retinogenesis

Proper organ patterning depends on a tight coordination between cell proliferation and differentiation. The patterning of Drosophila retina occurs both very fast and with high precision. This process is driven by the dynamic changes in signaling activity of the conserved Hedgehog (Hh) pathway, which coordinates cell fate determination, cell cycle and tissue morphogenesis. Here we show that during Drosophila retinogenesis, the retinal determination gene dachshund (dac) is not only a target of the Hh signaling pathway, but is also a modulator of its activity. Using developmental genetics techniques, we demonstrate that dac enhances Hh signaling by promoting the accumulation of the Gli transcription factor Cubitus interruptus (Ci) parallel to or downstream of fused. In the absence of dac, all Hh-mediated events associated to the morphogenetic furrow are delayed. One of the consequences is that, posterior to the furrow, dac- cells cannot activate a Roadkill-Cullin3 negative feedback loop that attenuates Hh signaling and which is necessary for retinal cells to continue normal differentiation. Therefore, dac is part of an essential positive feedback loop in the Hh pathway, guaranteeing the speed and the accuracy of Drosophila retinogenesis.

FACS-based purification of Arabidopsis microspores, sperm cells and vegetative nuclei

Background: The male germline in flowering plants differentiates by asymmetric division of haploid uninucleated microspores, giving rise to a vegetative cell enclosing a smaller generative cell, which eventually undergoes a second mitosis to originate two sperm cells. The vegetative cell and the sperm cells activate distinct genetic and epigenetic mechanisms to control pollen tube growth and germ cell specification, respectively. Therefore, a comprehensive characterization of these processes relies on efficient methods to isolate each of the different cell types throughout male gametogenesis. Results: We developed stable transgenic Arabidopsis lines and reliable purification tools based on Fluorescence-Activated Cell Sorting (FACS) in order to isolate highly pure and viable fractions of each cell/nuclei type before and after pollen mitosis. In the case of mature pollen, this was accomplished by expressing GFP and RFP in the sperm and vegetative nuclei, respectively, resulting in 99% pure sorted populations. Microspores were also purified by FACS taking advantage of their characteristic small size and autofluorescent properties, and were confirmed to be 98% pure. Conclusions: We provide simple and efficient FACS-based purification protocols for Arabidopsis microspores, vegetative nuclei and sperm cells. This paves the way for subsequent molecular analysis such as transcriptomics, DNA methylation analysis and chromatin immunoprecipitation, in the developmental context of microgametogenesis in Arabidopsis.

Reprogramming of DNA Methylation in Pollen Guides Epigenetic Inheritance via Small RNA

Epigenetic inheritance is more widespread in plants than in mammals, in part because mammals erase epigenetic information by germline reprogramming. We sequenced the methylome of three haploid cell types from developing pollen: the sperm cell, the vegetative cell, and their precursor, the postmeiotic microspore, and found that unlike in mammals the plant germline retains CG and CHG DNA methylation. However, CHH methylation is lost from retrotransposons in microspores and sperm cells and restored by de novo DNA methyltransferase guided by 24 nt small interfering RNA, both in the vegetative nucleus and in the embryo after fertilization. In the vegetative nucleus, CG methylation is lost from targets of DEMETER (DME), REPRESSOR OF SILENCING 1 (ROS1), and their homologs, which include imprinted loci and recurrent epialleles that accumulate corresponding small RNA and are premethylated in sperm. Thus genome reprogramming in pollen contributes to epigenetic inheritance, transposon silencing, and imprinting, guided by small RNA.

Targeting the serrated pathway of colorectal cancer with mutation in BRAF

A recently acknowledged morphological pathway to colorectal cancer originates from precursor polyps with a serrated appearance due to branching and folding of the colon epithelium. This serrated origin accounts for up to 30% of all colorectal tumors but these are heterogeneous regarding molecular characteristics and patient outcome. Here we review the current knowledge about the classification of this tumor subtype and its association with five key features: mutation status of the BRAF or KRAS genes, the CpG island methylation phenotype, microsatellite instability, immune cell infiltration, and overexpression of GTPase RAC1b. Subsequently, available therapeutic approaches for targeting these molecular characteristics are presented and critically discussed.

Regulatory crosstalk by protein kinases on CFTR trafficking and activity

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a member of the ATP binding cassette (ABC) transporter superfamily that functions as a cAMP-activated chloride ion channel in fluid-transporting epithelia. There is abundant evidence that CFTR activity (i.e., channel opening and closing) is regulated by protein kinases and phosphatases via phosphorylation and dephosphorylation. Here, we review recent evidence for the role of protein kinases in regulation of CFTR delivery to and retention in the plasma membrane. We review this information in a broader context of regulation of other transporters by protein kinases because the overall functional output of transporters involves the integrated control of both their number at the plasma membrane and their specific activity. While many details of the regulation of intracellular distribution of CFTR and other transporters remain to be elucidated, we hope that this review will motivate research providing new insights into how protein kinases control membrane transport to impact health and disease.