The Triassic-Jurassic boundary in eastern North America

Rift basins of the Atlantic passive margin in eastern North America are filled with thousands of meters of continental rocks termed the Newark Supergroup which provide an unprecedented opportunity to examine the fine scale structure of the Triassic-Jurassic mass extinction in continental environments. Time control, vital to the understanding of the mechanisms behind mass extinctions, is provided by lake-level cycles apparently controlled by orbitally induced climate change allowing resolution at the less than 21,000 year level. Correlation with other provinces is provided by a developing high resolution magnetostratigraphy and palynologically-based biostratigraphy. A large number of at least local vertebrate and palynomorph extinctions are concentrated around the boundary with survivors constituting the earliest Jurassic assemblages, apparently without the introduction of new taxa. The palynofloral transition is marked by the dramatic elimination of a relatively high diversity Triassic pollen assemblage with the survivors making up a Jurassic assemblage of very low diversity overwhelmingly dominated by Corollina. Based principally on palynological correlations, the hypothesis that these continental taxonomic transitions were synchronous with the massive Triassic-Jurassic marine extinctions is strongly corroborated. An extremely rapid, perhaps catastrophic, taxonomic turnover at the Triassic-Jurassic boundary, synchronous in continental and marine realms is hypothesized and discussed

Computation of the Transient in Max-Plus Linear Systems via SMT-Solving

This paper proposes a new approach, grounded in Satisfiability Modulo Theories (SMT), to study the transient of a Max-Plus Linear (MPL) system, that is the number of steps leading to its periodic regime. Differently from state-of-the-art techniques, our approach allows the analysis of periodic behaviors for subsets of initial states, as well as the characterization of sets of initial states exhibiting the same specific periodic behavior and transient. Our experiments show that the proposed technique dramatically outperforms state-of-the-art methods based on max-plus algebra computations for systems of large dimensions.Comment: The paper consists of 22 pages (including references and Appendix). It is accepted in FORMATS 2020 First revisio

The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis

Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P = 1.34×10<sup>−8</sup>, OR = 1.22, CI 95% = 1.14–1.30; rs2004640: P = 4.60×10<sup>−7</sup>, OR = 0.84, CI 95% = 0.78–0.90; rs10488631: P = 7.53×10<sup>−20</sup>, OR = 1.63, CI 95% = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P = 9.04×10<sup>−22</sup>, OR = 1.75, CI 95% = 1.56–1.97) better explained the observed association (likelihood P-value = 1.48×10<sup>−4</sup>), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that this association is not sub-phenotype-specific

Megabank found? Flanks record sea level

On Leg 101, the first international voyage for the Ocean Drilling Program, the deep-sea drilling ship JOIOES Resolution (SEDCO/BP 471) left Miami, Fla., on Jan. 31 to investigate the geology of the Bahamas. (Leg 100 tested the Resolution's readiness. See July Geotimes.) Before returning to Miami on March 14, the crew had drilled 19 holes al 11 sites and recovered 46.2% of the cored section (about 1.5 of 3.1 km cored). The scientific party wanted to test conflicting hypotheses about the development of the modern shallow water carbonate banks and intervening deep -water throughs in the Bahamas, and to study the growth patterns of carbonate slopes and their response to sea-level fluctuations. Those objectives (the 'deep ' and the 'shallow') were selected beause recent advances in interpreting the micropaleontology of shallow-water carbonate platforms, coupled with data from previous sedimentological investigations and regional and site-specific seismic surveys, now permit consistent stratigraphic comparisons in the Bahamas

Efectos adversos neuropsiquiátricos de dolutegravir en la práctica clínica real

Introducción Los inhibidores de la integrasa, y especialmente dolutegravir (DTG), son el tratamiento de primera línea antirretroviral por su eficacia y seguridad. Aunque en los ensayos pivotales la tasa de efectos adversos (EA) era baja (2-3%), en los estudios de vida real parece ser mayor, especialmente los EA neuropsiquiátricos. El objetivo fue determinar el porcentaje de EA e interrupción de DTG en nuestro centro y la relación con los antecedentes psiquiátricos. Métodos Estudio descriptivo retrospectivo de pacientes que iniciaron DTG entre 2015-2017. Se registraron: interrupción del tratamiento, EA y enfermedad psiquiátrica. Se realizó seguimiento desde el inicio del del tratamiento con DTG y se registraron las hospitalizaciones y las visitas a urgencias y atención primaria. Fue autorizado por el Comité Ético de Investigación Clínica de Aragón. Resultados Se incluyeron 283 pacientes, entre 11-87 años, 70% varones. El 21% naive. Interrumpieron el tratamiento con DTG el 24%, un 10% por EA. Se detectó un 5% de EA neuropsiquiátricos. Este grupo tenía más antecedentes psiquiátricos (62 vs. 41%; p = 0, 002) que el de pacientes que continuaron el tratamiento, y precisaron más visitas en atención primaria (18, 8 vs. 8, 4%; p = 0, 016) y urgencias (8, 7 vs. 3, 3%; p = 0, 061). Conclusión Los pacientes que interrumpieron el tratamiento con DTG tenían más antecedentes psiquiátricos. Por ello, aunque se precisan más estudios, sería necesario valorar este antecedente previamente al tratamiento con inhibidores de la integrasa. Síntomas como ansiedad, insomnio o depresión pueden ser EA de DTG con una frecuencia mayor de la esperada. Ser identificados por los médicos de atención primaria y urgencias podría evitar una cascada de prescripción innecesaria. Introduction: Integrase inhibitors and especially dolutegravir (DTG) are placed as a first-line antiretroviral treatment for their efficacy and safety. Although in the pivotal trials the rate of adverse effects (AEs) was low (2-3%), in real-life studies it appears to be higher, especially neuropsychiatric AEs. The objective is to determine the percentage of AEs and discontinuation of DTG in our site and the relationship with the psychiatric background. Methods: Retrospective descriptive study of patients starting DTG from 2015 to 2017. Discontinuation of treatment, AEs and previous psychiatric pathology were recorded. Follow-up is carried out since the beginning of the treatment, and hospitalizations and emergency room and primary care visits were registered. The study was authorized by the Ethics Committee for Clinical Research of Aragon. Results: Two hundred and eighty-three patients were included, between 11 and 87 years old, 70% male. 21% were naive. 24% of the patients discontinued treatment with DTG, 10% due to AEs. Neuropsychiatric AEs were detected in 5%. This group of patients had a more frequent previous psychiatric history (62 vs. 41%; P =.002) than the ongoing treatment group and they needed more visits to primary care (18.8 vs. 8.4%; P =.016) and emergency room (8, 7 vs. 3.3%; P =.061). Conclusion: Patients who discontinued treatment with DTG had more psychiatric history. Although more studies are required, it is necessary to assess this background before starting treatment with integrase inhibitors. Symptoms such as anxiety, insomnia or depression can be DTG AEs more frequently than expected. Being identified by primary care and emergency physicians could avoid the unnecessary prescription of other medications

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.<p></p> Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.<p></p> Conclusion: Our results suggest a role of PPARG gene in the development of SSc

Exceptional preservation of palaeozoic steroids in a diagenetic continuum

The occurrence of intact sterols has been restricted to immature Cretaceous (~125 Ma) sediments with one report from the Late Jurassic (~165 Ma). Here we report the oldest occurrence of intact sterols in a Crustacean fossil preserved for ca. 380 Ma within a Devonian concretion. The exceptional preservation of the biomass is attributed to microbially induced carbonate encapsulation, preventing full decomposition and transformation thus extending sterol occurrences in the geosphere by 250 Ma. A suite of diagenetic transformation products of sterols was also identified in the concretion, demonstrating the remarkable coexistence of biomolecules and geomolecules in the same sample. Most importantly the original biolipids were found to be the most abundant steroids in the sample. We attribute the coexistence of steroids in a diagenetic continuum-ranging from stenols to triaromatic steroids-to microbially mediated eogenetic processes

Testing statistical significance scores of sequence comparison methods with structure similarity

BACKGROUND: In the past years the Smith-Waterman sequence comparison algorithm has gained popularity due to improved implementations and rapidly increasing computing power. However, the quality and sensitivity of a database search is not only determined by the algorithm but also by the statistical significance testing for an alignment. The e-value is the most commonly used statistical validation method for sequence database searching. The CluSTr database and the Protein World database have been created using an alternative statistical significance test: a Z-score based on Monte-Carlo statistics. Several papers have described the superiority of the Z-score as compared to the e-value, using simulated data. We were interested if this could be validated when applied to existing, evolutionary related protein sequences. RESULTS: All experiments are performed on the ASTRAL SCOP database. The Smith-Waterman sequence comparison algorithm with both e-value and Z-score statistics is evaluated, using ROC, CVE and AP measures. The BLAST and FASTA algorithms are used as reference. We find that two out of three Smith-Waterman implementations with e-value are better at predicting structural similarities between proteins than the Smith-Waterman implementation with Z-score. SSEARCH especially has very high scores. CONCLUSION: The compute intensive Z-score does not have a clear advantage over the e-value. The Smith-Waterman implementations give generally better results than their heuristic counterparts. We recommend using the SSEARCH algorithm combined with e-values for pairwise sequence comparisons

Modelling and Analysing Genetic Networks: From Boolean Networks to Petri Nets

Abstract. In order to understand complex genetic regulatory networks researchers require automated formal modelling techniques that provide appropriate analysis tools. In this paper we propose a new qualitative model for genetic regulatory networks based on Petri nets and detail a process for automatically constructing these models using logic mini-mization. We take as our starting point the Boolean network approach in which regulatory entities are viewed abstractly as binary switches. The idea is to extract terms representing a Boolean network using logic minimization and to then directly translate these terms into appropri-ate Petri net control structures. The resulting compact Petri net model addresses a number of shortcomings associated with Boolean networks and is particularly suited to analysis using the wide range of Petri net tools. We demonstrate our approach by presenting a detailed case study in which the genetic regulatory network underlying the nutritional stress response in Escherichia coli is modelled and analysed.