Explore the vast range of titles available.

Ash fall layers and vitroclastic-carrying sediments distributed throughout the entire Permian stratigraphic range of the Parana Basin (Brazil and Uruguay) occur in the Tubarao Supergroup (Rio Bonito Formation) and the Passa Dois Group (Irati, Estrada Nova/Teresina, Corumbatai, and Rio do Rasto Formations), which constitute the Gondwana 1 Supersequence. U-Pb zircon ages, acquired by SHRIMP and isotope-dissolution thermal ionization mass spectrometer (ID-TIMS) from tuffs within the Mangrullo and Yaguari Formations of Uruguay, are compatible with a correlation with the Irati and parts of the Teresina and Rio do Rasto Formations, respectively, of Brazil. U-Pb zircon ages suggest maximum depositional ages for the samples: (1) Rio Bonito Formation: ages ranging from 295.8±3.1 to 304.0±5.6 Ma (Asselian, lowermost Permian), consistent with the age range of the Protohaploxypinus goraiensis subzone; (2) Irati Formation: ages ranging from 279.9±4.8 to 280.0±3.0 Ma (Artinskian, Middle Permian), consistent with the occurrence of species of the Lueckisporites virkkiae zone; (3) Rio do Rasto Formation: ages ranging from 266.7±5.4 to 274.6±6.3 Ma (Wordian to Roadian, Middle Permian). All the SHRIMP U-Pb zircon ages are consistent with their superimposition order in the stratigraphy, the latest revisions to the Permian timescale (International Commission of Stratigraphy, 2018 version), and the most recent appraisals of biostratigraphic data. The ID-TIMS U-Pb zircon ages from the Corumbatai Formation suggest that U-Pb ages may be >10% younger than interpreted biostratigraphic ages.

The Itajaí Basin located in the southern border of the Luís Alves Microplate is considered as a peripheral foreland basin related to the Dom Feliciano Belt. It presents an excellent record of the Ediacaran period, and its upper parts display the best Brazilian example of Precambrian turbiditic deposits. The basal succession of Itajaí Group is represented by sandstones and conglomerates (Baú Formation) deposited in alluvial and deltaic-fan systems. The marine upper sequences correspond to the Ribeirão Carvalho (channelized and non-channelized proximal silty-argillaceous rhythmic turbidites), Ribeirão Neisse (arkosic sandstones and siltites), and Ribeirão do Bode (distal silty turbidites) formations. The Apiúna Formation felsic volcanic rocks crosscut the sedimentary succession. The Cambrian Subida leucosyenogranite represents the last felsic magmatic activity to affect the Itajaí Basin. The Brusque Group and the Florianópolis Batholith are proposed as source areas for the sediments of the upper sequence. For the lower continental units the source areas are the Santa Catarina, São Miguel and Camboriú complexes. The lack of any oceanic crust in the Itajaí Basin suggests that the marine units were deposited in a restricted, internal sea. The sedimentation started around 600 Ma and ended before 560 Ma as indicated by the emplacement of rhyolitic domes. The Itajaí Basin is temporally and tectonically correlated with the Camaquã Basin in Rio Grande do Sul and the Arroyo del Soldado/Piriápolis Basin in Uruguay. It also has several tectono-sedimentary characteristics in common with the African-equivalent Nama Basin.

The Mantiqueira Province represents a series of supracrustal segments of the South-American counterpart formed during the Gondwana Supercontinent agglutination. In this crustal domain, the process of escape tectonics played a conspicuous role, generating important NE–N–S-trending lineaments. The oblique component of the motions of the colliding tectonic blocks defined the transpressional character of the main suture zones: Lancinha-Itariri, Cubatão-Arcádia-Areal, Serrinha-Rio Palmital in the Ribeira Belt and Sierra Ballena-Major Gercino in the Dom Feliciano Belt. The process as a whole lasted for ca. 60 Ma, since the initial collision phase until the lateral escape phase predominantly marked by dextral and subordinate sinistral transpressional shear zones. In the Dom Feliciano Belt, southern Brazil and Uruguay, transpressional event at 630–600 Ma is recognized and in the Ribeira Belt, despite less coevally, the transpressional event occurred between 590 and 560 Ma in its northern-central portion and between ca . 625 and 595 Ma in its central-southern portion. The kinematics of several shear zones with simultaneous movement in opposite directions at their terminations is explained by the sinuosity of these lineaments in relation to a predominantly continuous westward compression.

The MITO-END3 trial compared carboplatin and paclitaxel (CP) with avelumab plus carboplatin and paclitaxel (CPA) as first-line treatment in endometrial cancer (EC) patients and demonstrated a significant interaction between avelumab response and mismatch repair status. To investigate prognostic/predictive biomarker, 29 MITO-END3-EC patients were evaluated at pretreatment (B1) and at the end of CP/CPA treatment (B2) for peripheral myeloid-derived suppressor cells (MDSC) and Tregs. At B2, effector Tregs frequency was significantly higher in patients treated with CPA as compared to CP ( p  = 0.038). Both treatments (CP/CPA) induced significant decrease in peripheral M-MDSC (− 5.41%) in TCGA 2-MSI-high as compared to TCGA-category 4 tumors ( p  = 0.004). In accordance, both treatments induced M-MDSCs (+ 5.34%) in MSS patients as compared to MSI-high patients ( p  = 0.001). Moreover, in a subgroup of patients, primary tumors were highly infiltrated by M-MDSCs in MSS as compared to MSI-high ECs. A post hoc analysis displayed higher frequency of M-MDSCs ( p  = 0.020) and lower frequency of CD4+ ( p  < 0.005) at pretreatment in EC patients as compared to healthy donors. In conclusion, the peripheral evaluation of MDSCs and Tregs correlated with molecular features in EC treated with CP/CPA and may add insights in identifying EC patients responder to first-line chemo/chemo-immunotherapy. Graphical abstract

ObjectivesTo analyse the prevalence of CECR1 mutations in patients diagnosed with early onset livedo reticularis and/or haemorrhagic/ischaemic strokes in the context of inflammation or polyarteritis nodosa (PAN). Forty-eight patients from 43 families were included in the study.MethodsDirect sequencing of CECR1 was performed by Sanger analysis. Adenosine deaminase 2 (ADA2) enzymatic activity was analysed in monocyte isolated from patients and healthy controls incubated with adenosine and with or without an ADA1 inhibitor.ResultsBiallelic homozygous or compound heterozygous CECR1 mutations were detected in 15/48 patients. A heterozygous disease-associated mutation (p.G47V) was observed in two affected brothers. The mean age of onset of the genetically positive patients was 24 months (6 months to 7 years). Ten patients displayed one or more cerebral strokes during their disease course. Low immunoglobulin levels were detected in six patients. Thalidomide and anti-TNF (tumour necrosis factor) blockers were the most effective drugs. Patients without CECR1 mutations had a later age at disease onset, a lower prevalence of neurological and skin manifestations; one of these patients displayed all the clinical features of adenosine deaminase 2deficiency (DADA2) and a defective enzymatic activity suggesting the presence of a missed mutation or a synthesis defect.ConclusionsDADA2 accounts for paediatric patients diagnosed with PAN-like disease and strokes and might explain an unrecognised condition in patients followed by adult rheumatologist. Timely diagnosis and treatment with anti-TNF agents are crucial for the prevention of severe complications of the disease. Functional assay to measure ADA2 activity should complement genetic testing in patients with non-confirming genotypes.

Adenomas and serrated lesions represent heterogeneous sets of early precursors in the colorectum with varying malignant potential. They are often distinguished by their histopathologic differences, but little is known about potential differences in regulation of epithelial proliferation and apoptosis. We conducted a protein expression analysis using tissue microarrays of 625 colorectal adenomas and 142 serrated lesions to determine potential differences in regulation of epithelial proliferation and apoptosis. We quantitated proliferation with Ki-67; apoptosis with activated caspase-3 (CASP3); up- and down-regulators of proliferation with cyclin D1, p16INK2, and p21Cip1; and apoptosis regulators with BAX, BCL2, and survivin. Linear mixed effects models and circos diagrams were used to determine relationships among expression and lesion characteristics. Adenomas had a significantly higher CASP-3 labeling index (LI) than serrated lesions, resulting in a lower net growth ratio (Ki-67 LI/activated CASP-3 LI, p-value<0.0001). Cyclin D1 LI, p16 LI and p21 LI were lower in adenomas compared to serrated lesions, while expression of both BCL2 and BAX were higher (p <0.001). Among adenomas, cyclin D1 LI and p16 LI levels increased with greater villous component, and the highest BAX expression was detected in adenomas larger than 2 cm (both p<0.0001). Right-sided adenomas had higher CASP3 LI than left colorectal adenomas (p = 0.008). Significant differences in cyclin D1 LI, p21 LI and survivin LI were also observed across histopathologic subtypes of serrated lesions. Our findings demonstrate different patterns of regulatory protein expression in adenomas than serrated lesions, especially involving apoptosis. ClinicalTrials.gov Identifier: NCT00272324.

Prostate-specific antigen (PSA) levels have been used for detection and surveillance of prostate cancer (PCa). However, factors other than PCa—such as genetics—can impact PSA. Here we present findings from a genome-wide association study (GWAS) of PSA in 28,503 Kaiser Permanente whites and 17,428 men from replication cohorts. We detect 40 genome-wide significant ( P <5 × 10 −8 ) single-nucleotide polymorphisms (SNPs): 19 novel, 15 previously identified for PSA (14 of which were also PCa-associated), and 6 previously identified for PCa only. Further analysis incorporating PCa cases suggests that at least half of the 40 SNPs are PSA-associated independent of PCa. The 40 SNPs explain 9.5% of PSA variation in non-Hispanic whites, and the remaining GWAS SNPs explain an additional 31.7%; this percentage is higher in younger men, supporting the genetic basis of PSA levels. These findings provide important information about genetic markers for PSA that may improve PCa screening, thereby reducing over-diagnosis and over-treatment. Prostate-specific antigen is used as a biomarker of prostate cancer, but levels can be affected by other factors not related to cancer. Here, the authors find genes associated with prostate specific antigen levels in healthy men, which could be used to reduce over-diagnosis and over-treatment.

Most arthropod-borne and invertebrate viruses are orally ingested and commence infection in cells of the invertebrate intestine. Infection of secondary sites and eventual transmission to other hosts is hindered by basal lamina, a tightly interwoven and virus-impenetrable noncellular layer, lining the intestine and other organ cell layers. The mechanisms for viral escape across basal laminae are unknown. We describe an elegant mechanism mediated by a baculovirus-encoded fibroblast growth factor (vFGF) that signals a previously undescribed stepwise cascade of protease activation wherein matrix metalloproteases activate effector caspases, leading to remodeling of basal lamina lining tracheal cells associated with the intestine and culminating in the establishment of efficient systemic infections. Because FGFs coordinate diverse functions during development, metabolic processes, and tissue repair, it is plausible that the vFGF-mediated pathway described here is widely used during developmental and pathogenic processes that involve basal lamina remodeling.

Background Anemia remains a public health challenge in Ethiopia, affecting an estimated 56% of children under age 5 years, 23% of women of reproductive age and 18% of adult men. However, anemia etiology and the relative contribution of underlying risk factors for anemia remains unclear and has hindered implementation of anemia control programs. Methods/design Anemia Etiology in Ethiopia (AnemEE) is a population-based cross-sectional survey of six regions of Ethiopia that includes children, women of reproductive age, and men from regionally representative households. The survey will include detailed assessment of anemia, iron, inflammatory and nutritional biomarkers, diet, comorbidities, and other factors. The objectives of AnemEE are 1) to generate evidence for decision-making on the etiology of anemia in Ethiopia among men, women and children and 2) to simulate the potential effect of iron fortification and other interventions on the prevalence of anemia and risk of iron overload. Discussion AnemEE will provide the most comprehensive evaluation of anemia etiology in Ethiopia to date due to its detailed assessment of diet, biomarkers, infections and other risk factors in a population-based sample. By generating evidence and simulating potential interventions, AnemEE will inform the development of high-impact anemia control programs and policies. Trial registration ClinicalTrials.gov, NCT04002466 . Registered on 28 June 2019. Retrospectively registered.

Purpose We examined the interaction between common genetic bladder cancer variants, diet quality, and bladder cancer risk in a population-based case–control study conducted in New England.Methods At the time of enrollment, 806 bladder cancer cases and 974 controls provided a DNA sample and completed a diet history questionnaire. Diet quality was assessed using the 2010 Alternate Healthy Eating Index (AHEI-2010) score. Single nucleotide polymorphisms (SNPs) reported in genome-wide association studies to be associated with bladder cancer risk were combined into a polygenic risk score and also examined individually for interaction with the AHEI-2010. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression.ResultsA 1-standard deviation increase in polygenic risk score was associated with higher bladder cancer risk (OR, 1.34; 95% CI 1.21–1.49). Adherence to the AHEI-2010 was not associated with bladder cancer risk (OR, 0.99; 95% CI 0.98–1.00) and the polygenic risk score did not appear to modify the association between the AHEI-2010 and bladder cancer risk. In single-SNP analyses, rs8102137 (bladder cancer risk allele, C) modified the association between the AHEI-2010 total score and bladder cancer risk, with the strongest evidence for the AHEI-2010 long chain fat guideline (OR for TT, 0.92; 95% CI 0.87–0.98; OR for CT, 1.02; 95% CI 0.96–1.08; OR for CC, 1.03; 95% CI 0.93–1.14; p for interaction, 0.02).Conclusions In conclusion, rs8102137 near the cyclin E1 gene ( CCNE1 ) may be involved in gene–diet interactions for bladder cancer risk.