Facies analysis and chemostratigraphy of the Chattanooga Formation in Tenneesee and Alabama

Master of ScienceDepartment of GeologyKarin GoldbergThe black shales of the Late Devonian to Early Mississippian are known for their rich organic concentrations, serving as source rock and housing unconventional reservoirs. The primary driving mechanism for the high organic matter content of these mudstones is yet to be fully understood. Interpretation of the complex factors controlling deposition of these mudrocks is facilitated by an integration of sedimentologic and chemostratigraphic analysis. Facies analysis, coupled with hand-held X-ray fluorescence (HHXRF), inductively-coupled plasma mass spectrometry (ICP-MS), X-ray diffraction (XRD), tipping point and total organic carbon (TOC) analyses were performed to construct sedimentologic-chemostratigraphic logs that allowed the establishment of a stratigraphic framework, and evaluation of depositional parameters such as detrital input, primary productivity, and degree of oxygenation during the accumulation of the studied succession. The ultimate goal was to identify the controls on sedimentation and main switches in organic matter content of the Chattanooga Formation (Devonian of the Appalachian Basin) in outcrops in Tennessee (TN-1) and Alabama (AL-1). The facies associations indicate that these successions were deposited in deep-marine environments varying from hemipelagic-lower shoreface to pelagic settings. Three sequences were identified in the sedimentary successions at each location (sequences 1 through 3, from base to top). The succession at TN-1 shows an oxic to anoxic environment of deposition with TOC values increasing upward from 3.49-17.80 wt%, while AL-1 shows an anoxic to oxic depositional environment from base to the top of the succession, with decreasing TOC values from 13.3-5.32 wt%. The stratigraphic framework shows incomplete system tracts, which can be attributed to poor preservation of the sedimentary succession resulting from low subsidence rates, typical of epicontinental basins. The only complete sequence, with lowstand, transgressive and highstand system tracts, is sequence 1 at AL-1. The integration between sedimentological data and chemical indices suggests that high organic content (TOC>10%) is found in settings where high primary productivity coincides with bottom-water anoxia

Recognition and analysis of seismic facies in the rift successions of the Campos and Santos Basins

Peer reviewedPublisher PD

Análise sismoestratigráfica da seção rifte da Bacia de Santos, Brasil

The Santos Basin, despite its surmount significance due to the pre-salt reservoirs, has limited geological information well-logs, 3D seismic or good quality 2D seismic for the rift section. The present work aims at integrating seismic stratigraphic analysis and proposing a tectonic-stratigraphic evolution model for the rift section of the basin. Seismic stratigraphic analysis involved interpretation of reflectors, which is the base of seismic stratigraphic units identification and seismic facies characterization. The result was the definition of 16 seismic stratigraphic units, four seismic facies (including the sag), and the development of chronostratigraphic charts of events adapted to the seismic context. Based on the adaptation of the stacking patterns to tectonic activity changes model, it was possible to delimit the rift initiation system tract, the high tectonic activity system tract, the low tectonic activity system tract and the post-rift, represented by the sag. The development of each tectonic system tract responded to variations in controlling factors of the lacustrine basin, interpreted as the relative balance between the rate changes in the accommodation space generated by tectonic and sediment supply influenced by climate.A Bacia de Santos, apesar de uma das principais bacias atualmente no Brasil exploradas devido à importância do pré-sal, possui pouca informação geológica, como registros de poço, sísmica 3D e sísmica 2D de boa qualidade na seção rifte. O presente trabalho visa à integração da análise sismoestratigráfica e proposição de um modelo de evolução tectonoestratigráfica para a seção rifte da bacia. A análise sismoestratigráfica envolveu a interpretação dos refletores, que é a base da identificação das unidades sismoestratigráficas e a caracterização das sismofácies. Como resultado, foi obtida a definição de 16 unidades sismoestratigráficas e quatro sismofácies (incluindo o sag), e o desenvolvimento das cartas cronoestratigráficas de eventos adaptadas para o contexto sísmico. Com base no ajuste do modelo de padrões de empilhamento para mudanças na atividade tectônica, foram delimitados os tratos de sistemas tectônicos de início de rifte, de alta atividade tectônica, de baixa atividade tectônica e o pós-rifte, representado pelo sag. O desenvolvimento de cada um dos tratos respondeu a variações dos fatores controladores das bacias lacustres, interpretado como o balanço relativo entre as taxas de mudanças do espaço de acomodação gerado pela tectônica e o aporte sedimentar influenciado pelo clima

Carbon isotopes, stratigraphy, and environmental change: the Middle–Upper Cambrian Positive Excursion (SPICE) in Port au Port Group, western Newfoundland, Canada

In many basins, Upper Cambrian carbonate successions display intervals with a positive carbon isotope excursion (CIE) of up to +5‰. In North America, this marks the boundary between the Sauk II–III super-sequences. A Steptoean positive carbon isotope excursion (SPICE) locality previously identified in the Port au Port peninsula, western Newfoundland, has been revisited and an additional potential SPICE locality found. In both locations, a CIE is found to be associated with a prominent bioherm and sandstone layer within a sequence of carbonate rocks. At March Point columnar stromatolites occur, whereas at Felix Cove thrombolites can be seen. In the latter, the sandstone immediately overlies the thrombolites coincident with the CIE, whereas at March Point a dolomitized grainstone occurs above the stromatolites. The sandstone at this locality post-dates the CIE. Although lower than the SPICE in some localities, a positive CIE is present in both sections: March Point (+1.1‰) and Felix Cove (+1.8‰). Additionally, δ13Corg rises from −30.0‰ to −22.0‰ at March Point and from −27‰ to −24.0‰ at Felix Cove and, in accordance with previously published work, we suggest that this could be the SPICE. Comparison of the stratigraphy and petrography between the two localities suggest that both depositional and diagenetic factors could have influenced the nature of the interpreted SPICE in Newfoundland. It is also possible that the local carbon isotopic signature may have been influenced by a semi-restricted depositional and early diagenetic environment related to the paleogeographic configuration rather than the global marine excursion

Expression of CXCL10 is associated with response to radiotherapy and overall survival in squamous cell carcinoma of the tongue

Five-year survival for patients with oral cancer has been disappointingly stable during the last decades, creating a demand for new biomarkers and treatment targets. Lately, much focus has been set on immunomodulation as a possible treatment or an adjuvant increasing sensitivity to conventional treatments. The objective of this study was to evaluate the prognostic importance of response to radiotherapy in tongue carcinoma patients as well as the expression of the CXC-chemokines in correlation to radiation response in the same group of tumours. Thirty-eight patients with tongue carcinoma that had received radiotherapy followed by surgery were included. The prognostic impact of pathological response to radiotherapy, N-status, T-stage, age and gender was evaluated using Cox's regression models, Kaplan-Meier survival curves and chi-square test. The expression of 23 CXC-chemokine ligands and their receptors were evaluated in all patients using microarray and qPCR and correlated with response to treatment using logistic regression. Pathological response to radiotherapy was independently associated to overall survival with a 2-year survival probability of 81 % for patients showing a complete pathological response, while patients with a non-complete response only had a probability of 42 % to survive for 2 years (p = 0.016). The expression of one CXC-chemokine, CXCL10, was significantly associated with response to radiotherapy and the group of patients with the highest CXCL10 expression responded, especially poorly (p = 0.01). CXCL10 is a potential marker for response to radiotherapy and overall survival in patients with squamous cell carcinoma of the tongue

Constitutional mismatch repair deficiency–associated brain tumors: report from the European C4CMMRD consortium

Abstract Background Malignant brain tumors (BT) are among the cancers most frequently associated with constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations in mismatch repair genes. This study analyzed data from the European "Care for CMMRD" (C4CMMRD) database to describe their clinical characteristics, treatments, and outcome with the aim of improving its diagnosis/treatment. Methods Retrospective analysis of data on patients with CMMRD and malignant BT from the C4CMMRD database up to July 2017. Results Among the 87 registered patients, 49 developed 56 malignant BTs: 50 high-grade gliomas (HGG) (with giant multinucleated cells in 16/21 histologically reviewed tumors) and 6 embryonal tumors. The median age at first BT was 9.2 years [1.1–40.6], with nine patients older than 18. Twenty-seven patients developed multiple malignancies (including16 before the BT). Most patients received standard treatment, and eight patients immunotherapy for relapsed HGG. The 3- and 5-year overall survival (OS) rates were 30% (95% CI: 19–45) and 22% (95% CI: 12–37) after the first BT, with worse prognosis for HGG (3-year OS = 20.5%). Six patients were alive (median follow-up 2.5 years) and 43 dead (38 deaths, 88%, were BT-related). Other CMMRD-specific features were café-au-lait macules (40/41), multiple BTs (5/15), developmental brain anomalies (11/15), and consanguinity (20/38 families). Conclusions Several characteristics could help suspecting CMMRD in pediatric malignant BTs: giant cells on histology, previous malignancies, parental consanguinity, café-au-lait macules, multiple BTs, and developmental brain anomalies. The prognosis of CMMRD-associated BT treated with standard therapies is poor requiring new therapeutic up-front approaches

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Regulation of Postsynaptic Function by the Dementia-Related ESCRT-III Subunit CHMP2B

The charged multivesicular body proteins (Chmp1–7) are an evolutionarily conserved family of cytosolic proteins that transiently assembles into helical polymers that change the curvature of cellular membrane domains. Mutations in human CHMP2B cause frontotemporal dementia, suggesting that this protein may normally control some neuron-specific process. Here, we examined the function, localization, and interactions of neuronal Chmp2b. The protein was highly expressed in mouse brain and could be readily detected in neuronal dendrites and spines. Depletion of endogenous Chmp2b reduced dendritic branching of cultured hippocampal neurons, decreased excitatory synapse density in vitro and in vivo, and abolished activity-induced spine enlargement and synaptic potentiation. To understand the synaptic effects of Chmp2b, we determined its ultrastructural distribution by quantitative immuno-electron microscopy and its biochemical interactions by coimmunoprecipitation and mass spectrometry. In the hippocampus in situ, a subset of neuronal Chmp2b was shown to concentrate beneath the perisynaptic membrane of dendritic spines. In synaptoneurosome lysates, Chmp2b was stably bound to a large complex containing other members of the Chmp family, as well as postsynaptic scaffolds. The supramolecular Chmp assembly detected here corresponds to a stable form of the endosomal sorting complex required for transport-III (ESCRT-III), a ubiquitous cytoplasmic protein complex known to play a central role in remodeling of lipid membranes. We conclude that Chmp2b-containing ESCRT-III complexes are also present at dendritic spines, where they regulate synaptic plasticity. We propose that synaptic ESCRT-III filaments may function as a novel element of the submembrane cytoskeleton of spines

Lipopolysaccharide and Tumor Necrosis Factor Regulate Parkin Expression via Nuclear Factor-Kappa B

Inflammation and oxidative stress have been implicated in the pathophysiology of Parkinson's disease (PD) and inhibition of microglial activation attenuates degeneration of dopaminergic (DA) neurons in animal models of PD. Loss-of-function mutations in the parkin gene, which encodes an E3 ubiquitin ligase, cause autosomal recessive parkinsonism. While most studies on Parkin have focused on its function in neurons, here we demonstrate that Parkin mRNA and protein is detectable in brain-resident microglia and peripheral macrophages. Using pharmacologic and genetic approaches, we found that Parkin levels are regulated by inflammatory signaling. Specifically, exposure to LPS or Tumor Necrosis Factor (TNF) induced a transient and dose-dependent decrease in Parkin mRNA and protein in microglia, macrophages and neuronal cells blockable by inhibitors of Nuclear Factor-Kappa B (NF-κB) signaling and not observed in MyD88-null cells. Moreover, using luciferase reporter assays, we identified an NF-κB response element in the mouse parkin promoter responsible for mediating the transcriptional repression, which was abrogated when the consensus sequence was mutated. Functionally, activated macrophages from Parkin-null mice displayed increased levels of TNF, IL-1β, and iNOS mRNA compared to wild type macrophages but no difference in levels of Nrf2, HO-1, or NQO1. One implication of our findings is that chronic inflammatory conditions may reduce Parkin levels and phenocopy parkin loss-of-function mutations, thereby increasing the vulnerability for degeneration of the nigrostriatal pathway and development of PD