Paleomagnetism of Middle Miocene Volcanic Rocks in the Mojave-Sonora Desert Region of Western Arizona and Southeastern California

Paleomagnetic directions have been obtained from 190 early to middle Miocene (12–20 Ma) mafic volcanic flows in 16 mountain ranges in the Mojave-Sonora desert region of western Arizona and southeastern California. These flows generally postdate early Miocene tectonic deformation accommodated by low-angle normal faults but predate high-angle normal faulting in the region. After detailed demagnetization experiments, 179 flows yielded characteristic directions interpreted as original thermal remanent magnetizations (TRM). Because of the episodic nature of basaltic volcanism in this region, the 179 flows yielded only 65 time-distinct virtual geomagnetic poles (VGPs). The angular dispersion of the 65 VGPs is consistent with the angular dispersion expected for a data set that has adequately averaged geomagnetic secular variation. The paleomagnetic pole calculated from the 65 cooling unit VGPs is located at 85.5°N, 108.9° within a 4.4° circle of 95% confidence. This pole is statistically indistinguishable (at 95% confidence) from reference poles calculated from rocks of similar age in stable North America and from a paleomagnetic pole calculated from rocks of similar age in Baja California. The coincidence of paleomagnetic poles from the Mojave-Sonora desert region with reference poles from the stable continental interior indicates that (1) significant vertical axis net tectonic rotations have not accompanied post-middle Miocene high-angle normal faulting in this region; (2) there has been no detectable post-middle Miocene latitudinal transport of the region; and (3) long-term nondipole components of the middle Miocene geomagnetic field probably were no larger than those of the recent (0–5 Ma) geomagnetic field. In contrast, paleomagnetic data indicate vertical axis rotations of similar age rocks in the Transverse Ranges, the Eastern Transverse Ranges, and the Mojave Block. We speculate that a major structural discontinuity in the vicinity of the southeastward projection of the Death Valley fault zone separates western areas affected by vertical axis rotations from eastern areas that have not experienced such rotations

SARS-CoV-2 Mproinhibition by a zinc ion: structural features and hints for drug design

The first structure of the SARS-CoV-2 main protease in complex with an isolated zinc ion provides solid ground for the design of potent and selective metal-conjugated inhibitors

A magnetar powering the ordinary monster GRB 130427A?

We present the analysis of the extraordinarily bright Gamma-Ray Burst (GRB) 130427A under the hypothesis that the GRB central engine is an accretion-powered magnetar. In this framework, initially proposed to explain GRBs with precursor activity, the prompt emission is produced by accretion of matter onto a newly-born magnetar, and the observed power is related to the accretion rate. The emission is eventually halted if the centrifugal forces are able to pause accretion. We show that the X-ray and optical afterglow is well explained as the forward shock emission with a jet break plus a contribution from the spin-down of the magnetar. Our modelling does not require any contribution from the reverse shock, that may still influence the afterglow light curve at radio and mm frequencies, or in the optical at early times. We derive the magnetic field ($B\sim 10^{16}$ G) and the spin period ($P\sim 20$ ms) of the magnetar and obtain an independent estimate of the minimum luminosity for accretion. This minimum luminosity results well below the prompt emission luminosity of GRB 130427A, providing a strong consistency check for the scenario where the entire prompt emission is the result of continuous accretion onto the magnetar. This is in agreement with the relatively long spin period of the magnetar. GRB 130427A was a well monitored GRB showing a very standard behavior and, thus, is a well-suited benchmark to show that an accretion-powered magnetar gives a unique view of the properties of long GRBs.Comment: 5 pages, 1 figure, accepted for publication in MNRAS Letter

Memantine prodrug as a new agent for alzheimer’s disease

Hydrogen sulphide has recently drawn much attention due to its potent anti-inflammatory and neuroprotective roles in brain functions. The purpose of the current study was to exploit these beneficial properties of H 2 S to design a new agent for the treatment of Alzheimer’s disease (AD). To pursue our aims, we replaced the free amine group of memantine with an isothiocyanate functionality as a putative H 2 S-donor moiety. The new chemical entity, named memit, was then tested in vitro to determine whether it retains the pharmacological profile of the “native drug”, while also providing a source of H 2 S in the CNS. Indeed, Memit showed the ability to release H 2 S through a cysteine-mediated mechanism, thus generating memantine. Moreover, the new hybrid molecule exerts protective effects against neuronal inflammation and induces a drastic fall in ROS production. In addition, memit was also able to reduce the Aβ(1-42) self-induced aggregation and exerted cytoprotective effect against Aβ oligomers-induced damage in both human neurons and rat microglia cells. Finally, similarly to memantine, the new compound promotes autophagy, a complex process required for cellular homeostasis in cell survival that results to be altered in neurodegenerative diseases. In conclusion, our study revealed that memit is a prodrug of memantine. Further in vivo studies will be necessary to fully investigate the synergic or cumulative effects due to the H 2 S-releasing moiety and the native drug

REMOTE SENSING ANALYSIS IN THE ARCHAEOLOGICAL CONTEXT OF LICODIA EUBEA (CATANIA)

Archaeological research conducted at the site of Marineo, in the territory of Licodia Eubea (CT, Sicily, Italy), has revealed the existence of a group of evidence dating back to various periods, from the Neolithic to the Middle Ages. Particularly important is the presence of caves, documented through archaeological excavations at the end of the 1980s, subsequently resumed from 2017 to today. These caves were used for ritual activities, especially during the Middle Bronze Age (1450–1250 BC). The existence of numerous combustion structures associated with remains of a meal, as evidenced by remains oan f animal, and human bones in a secondary position, suggests the funerary value of the caves. Until now, however, data were missing on the identification of the settlement inhabited by communities that used caves. During the last archaeological excavation campaign, images and orthophotos were acquired through the use of drones. In this way, through the study of these images, it was possible to identify new anomalies in areas not yet investigated and placed in the vicinity of the caves. Surveys carried out in the area, have confirmed the presence of remains of walls belonging to curvilinear and oval structures. These structures are probably parts of the settlement connected to the caves whose exact location was not known until today. To support the excavation activity, GIS and remote sensing applications were implemented for predictive and postdictive analysis using only free and open source software and satellite images

Are Immune Modulating Single Nucleotide Polymorphisms Associated with Necrotizing Enterocolitis?

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48-29.39), and over 7 times more likely to have Stage III disease (p = 0.011; OR = 7.13, (95% CI 1.56-32.52). Neonates with TGFβ-1 (rs2241712) had a decreased incidence of NEC-related perforation (p = 0.044; OR = 0.28, 95% CI: 0.08-0.97) and an increased incidence of mortality (p = 0.049; OR = 2.99, 95% CI: 1.01 - 8.86). TRIM21 (rs660) was associated with NEC-related intestinal perforation (p = 0.038; OR = 4.65, 95% CI 1.09-19.78). In premature Caucasian neonates, the functional SNP IL-6 (rs1800795) is associated with both the development and increased severity of NEC. TRIM21 (rs660) and TGFβ-1 (rs2241712) were associated with NEC- related perforation in all neonates in the cohort. These findings suggest a possible genetic role in the development of NEC

Genomics in premature infants: A non-invasive strategy to obtain high-quality DNA

We used a cost-effective, non-invasive method to obtain high-quality DNA from buccal epithelial-cells (BEC) of premature infants for genomic analysis. DNAs from BEC were obtained from premature infants with gestational age ≤ 36 weeks. Short terminal repeats (STRs) were performed simultaneously on DNA obtained from the buccal swabs and blood from the same patient. The STR profiles demonstrated that the samples originated from the same individual and exclude any contamination by external DNAs. Whole exome sequencing was performed on DNAs obtained from BEC on premature infants with and without necrotizing enterocolitis, and successfully provided a total number of reads and variants corroborating with those obtained from healthy blood donors. We provide a proof of concept that BEC is a reliable and preferable source of DNA for high-throughput sequencing in premature infants

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol

Introduction: Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12–15% of patients with SSc and accounts for 30– 40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc- PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. Methods and analysis: This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethics and dissemination: Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals.Alicia Calderone, Wendy Stevens, David Prior, Harshal Nandurkar, Eli Gabbay, Susanna M Proudman, Trevor Williams, David Celermajer, Joanne Sahhar, Peter K K Wong, Vivek Thakkar, Nathan Dwyer, Jeremy Wrobel, Weng Chin, Danny Liew, Margaret Staples, Rachelle Buchbinder, Mandana Nikpou

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

Comparing the spectral lag of short and long gamma-ray bursts and its relation with the luminosity

We investigated the rest frame spectral lags of two complete samples of bright long (50) and short (6) gamma-ray bursts (GRB) detected by Swift. We analysed the Swift/BAT data through a discrete cross-correlation function (CCF) fitted with an asymmetric Gaussian function to estimate the lag and the associated uncertainty. We find that half of the long GRBs have a positive lag and half a lag consistent with zero. All short GRBs have lags consistent with zero. The distributions of the spectral lags for short and long GRBs have different average values. Limited by the small number of short GRBs, we cannot exclude at more than 2 sigma significance level that the two distributions of lags are drawn from the same parent population. If we consider the entire sample of long GRBs, we do not find evidence for a lag-luminosity correlation, rather the lag-luminosity plane appears filled on the left hand side, thus suggesting that the lag-luminosity correlation could be a boundary. Short GRBs are consistent with the long ones in the lag-luminosity plane.Comment: 11 pages, 6 figures, 2 tables, accepted for publication in MNRA