Development and characterization of tri- and tetra-nucleotide polymorphic microsatellite markers for skipjack tuna (Katsuwonus pelamis)

Skipjack tuna (katsuwonus pelamis) (SJT) is the largest tuna fishery in all the major oceans around the world, and the largest marine fishery in Sri Lanka. Knowledge of genetic population structure and effective population size of SJT in the Indian Ocean and other major oceans, however, is still lacking for better management practices and conservation strategies. We developed microsatellite genetic markers using SJT around Sri Lanka in the Indian Ocean, and characterise one tri- and seven tetra-nucleotide microsatellite loci isolated from enriched genomic libraries from SJT, to provide tools for addressing both conservation and fisheries management questions. An analysis of these eight microsatellite markers in two populations of SJT from eastern Sri Lanka (n = 44) and the Maldives Islands (n = 53) showed that all eight microsatellites were polymorphic with an average number of alleles per locus of 11.80 (range 5-27). Expected heterozygosities at marker loci ranged from 0.450 to 0.961. These markers are being used currently to characterise population structure and extent of natural gene flow in SJT populations from the eastern and western Indian Ocean. No significant linkage disequilibrium was detected among any loci pairs

Sismicità all’Etna dal 1989 al 2010: evidenze sull’evoluzione spazio-temporale dell’attività sismica

Il Monte Etna, uno dei più attivi vulcani basaltici tra i più monitorati al mondo, è sede di una notevole attività sismica e vulcanica. Esso è ubicato in Sicilia orientale in un complesso quadro geodinamico, dove le principali strutture tettoniche regionali giocano un ruolo chiave nei processi dinamici del vulcano. La sismicità dell’Etna si manifesta con un elevato rate di terremoti di bassa e moderata energia che, a volte, a causa dell’estrema superficialità della sorgente, provocano danni ai centri abitati prossimi all’area epicentrale. Il monitoraggio sistematico dell’attività sismica etnea è effettuato sin dal 1989, mediante una rete sismica locale permanente che nel tempo è stata oggetto di importanti miglioramenti. La prima configurazione di rete era costituita da circa 10 stazioni analogiche con sensori a corto periodo gestita dall’Istituto Internazionale di Vulcanologia (IIV-CNR). Nel 1994, una rete sismica costituita da circa 40 stazioni (analogiche con sensori a corto periodo) fu installata sull’Etna nell’ambito del Progetto Poseidon. Nel 2001, le reti gestite dall’IIV-CNR e dal Progetto Poseidon confluirono nell’Istituto Nazionale di Geofisica e Vulcanologia (INGV); attualmente la rete sismica, costituita da circa 50 stazioni digitali equipaggiate con sismometri broadband a tre componenti, è gestita dalla Sezione di Catania dell’INGV. Nel periodo 1989-1999, il catalogo dei terremoti risulta costituito da circa 2000 eventi con soglia di completezza per magnitudo pari a 2.0; dal 1999 ad oggi contiene circa 6000 terremoti con soglia di completezza per magnitudo 1.5. La capacità di detezione della rete è migliorata nel tempo permettendo di registrare e localizzare anche gli eventi meno energetici (M≥1.0). In questo lavoro, vengono presentati i caratteri predominanti della sismicità etnea negli ultimi 20 anni, con un maggiore dettaglio della distribuzione spazio-temporale della sismicità verificatasi dal 1999. L’analisi della attività sismica rappresenta un utile strumento per l’interpretazione delle dinamiche che hanno contraddistinto numerose ed importanti eruzioni (2001, 2002-03, 2004, 2006, 2008-09). In particolare, la variazione del rilascio energetico della sismicità ha contribuito in maniera significativa ad identificare i probabili processi geodinamici legati alla ricarica del sistema magmatico del vulcano. La distribuzione spaziale della sismicità ha consentito di evidenziare inoltre l’esistenza di diverse aree sismogenetiche caratterizzate da un differente rate sismico, profondità focali e cinematica delle strutture associate. Infine, osservando le caratteristiche della sismicità nel lungo periodo, differenti settori del vulcano sono risultati maggiormente attivi in relazione ai più importanti recenti eventi eruttivi

Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib

Objectives: In a phase Ib trial, afatinib plus cetuximab demonstrated promising clinical activity (objective response rate [ORR]: 29%; median progression-free survival [PFS]: 4.7 months) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with acquired resistance to erlotinib or gefitinib. Here, a separate cohort exploring afatinib plus cetuximab after progression on afatinib is reported. Materials and methods: Patients with EGFR mutation-positive NSCLC who progressed on erlotinib or gefitinib received afatinib 40 mg daily until progression, followed by afatinib daily plus cetuximab 500 mg/m(2) every 2 weeks until progression or intolerable adverse events (AEs). Endpoints included safety, ORR, and PFS. Results: Thirty-seven patients received afatinib monotherapy. Two (5%) patients responded; median PFS was 2.7 months. Thirty-six patients transitioned to afatinib plus cetuximab. Four (11%) patients responded; median PFS was 2.9 months. Median PFS with afatinib plus cetuximab for patients who received afatinib monotherapy for >= 12 versus <12 weeks was 4.9 versus 1.8 months (p = 0.0354), and for patients with T790M-positive versus T790M-negative tumors was 4.8 versus 1.8 months (p = 0.1306). Fifty percent of patients receiving afatinib plus cetuximab experienced drug-related grade 3/4 AEs. The most frequent drug-related AEs (any grade) were diarrhea (70%), rash (49%), and fatigue (35%) with afatinib monotherapy and rash (69%), paronychia (39%), and dry skin (36%) with afatinib plus cetuximab. Conclusion: Sequential EGFR blockade with afatinib followed by afatinib plus cetuximab had a predictable safety profile and demonstrated modest activity in patients with EGFR mutation-positive NSCLC with resistance to erlotinib or gefitinib

A Family of Diverse Kunitz Inhibitors from Echinococcus granulosus Potentially Involved in Host-Parasite Cross-Talk

The cestode Echinococcus granulosus, the agent of hydatidosis/echinococcosis, is remarkably well adapted to its definitive host. However, the molecular mechanisms underlying the successful establishment of larval worms (protoscoleces) in the dog duodenum are unknown. With the aim of identifying molecules participating in the E. granulosus-dog cross-talk, we surveyed the transcriptomes of protoscoleces and protoscoleces treated with pepsin at pH 2. This analysis identified a multigene family of secreted monodomain Kunitz proteins associated mostly with pepsin/H+-treated worms, suggesting that they play a role at the onset of infection. We present the relevant molecular features of eight members of the E. granulosus Kunitz family (EgKU-1 – EgKU-8). Although diverse, the family includes three pairs of close paralogs (EgKU-1/EgKU-4; EgKU-3/EgKU-8; EgKU-6/EgKU-7), which would be the products of recent gene duplications. In addition, we describe the purification of EgKU-1 and EgKU-8 from larval worms, and provide data indicating that some members of the family (notably, EgKU-3 and EgKU-8) are secreted by protoscoleces. Detailed kinetic studies with native EgKU-1 and EgKU-8 highlighted their functional diversity. Like most monodomain Kunitz proteins, EgKU-8 behaved as a slow, tight-binding inhibitor of serine proteases, with global inhibition constants (KI*) versus trypsins in the picomolar range. In sharp contrast, EgKU-1 did not inhibit any of the assayed peptidases. Interestingly, molecular modeling revealed structural elements associated with activity in Kunitz cation-channel blockers. We propose that this family of inhibitors has the potential to act at the E. granulosus-dog interface and interfere with host physiological processes at the initial stages of infection

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

Data Availability Statement: The individual-level data from these studies is not publicly available to main confidentiality. Data generated by the ISARIC4C consortium is available for collaborative analysis projects through an independent data and materials access committee at isaric4c.net/sample_access. Data and samples from the COVID-Clinical Neuroscience Study are available through collaborative research by application through the NIHR bioresource at https://bioresource.nihr.ac.uk/using-our-bioresource/apply-for-bioresource-data-access/. Brain injury marker and immune mediator data are present in the paper and in the source data file. Source data are provided with this paper.To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely.National Institute for Health and Care Research (NIHR) (CO-CIN-01) and jointly by NIHR and UK Research and Innovation (CV220-169, MC_PC_19059). B.D.M. is supported by the UKRI/MRC (MR/V03605X/1), the MRC/UKRI (MR/V007181/1), MRC (MR/T028750/1) and Wellcome (ISSF201902/3). C.D. is supported by MRC (MC_PC_19044). We would like to thank the University of Liverpool GCP laboratory facility team for Luminex assistance and the Liverpool University Biobank team for all their help, especially Dr. Victoria Shaw, Lara Lavelle-Langham, and Sue Holden. We would like to acknowledge the Liverpool Experimental Cancer Medicine Centre for providing infrastructure support for this research (Grant Reference: C18616/A25153). We acknowledge the Liverpool Centre for Cell Imaging (CCI) for provision of imaging equipment (Dragonfly confocal microscope) and excellent technical assistance (BBSRC grant number BB/R01390X/1). Tom Solomon is supported by The Pandemic Institute and the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool. D.K.M. and E.N. are supported by the NIHR Cambridge Biomedical Centre and by NIHR funding to the NIHR BioResource (RG94028 and RG85445), and by funding from Brain Research UK 201819-20. We thank NIHR BioResource volunteers for their participation, and gratefully acknowledge NIHR BioResource centres, NHS Trusts and staff for their contribution. We thank the National Institute for Health and Care Research, NHS Blood and Transplant, and Health Data Research UK as part of the Digital Innovation Hub Programme. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute. The authors would like to acknowledge the eDRIS team (Public Health Scotland) for their support in obtaining approvals, the provisioning and linking of data and facilitating access to the National Safe Haven. The views expressed are those of the author(s) and not necessarily those of the UKRI, NHS, the NIHR or the Department of Health and Social Care

Detection of extended TeV emission around the Geminga pulsar with H.E.S.S.

Highly extended gamma-ray emission around the Geminga pulsar was discovered by Milagro and verified by HAWC. Despite many observations with Imaging Atmospheric Cherenkov Telescopes (IACTs), detection of gamma-ray emission on angular scales exceeding the IACT field-of-view has proven challenging. Recent developments in analysis techniques have enabled the detection of significant emission around Geminga in archival data with H.E.S.S.. In 2019, further data on the Geminga region were obtained with an adapted observation strategy. Following the announcement of the detection of significant TeV emission around Geminga in archival data, in this contribution we present the detection in an independent dataset. New analysis results will be presented, and emphasis given to the technical challenges involved in observations of highly extended gamma-ray emission with IACTs

Astronomy outreach in Namibia : H.E.S.S. and beyond

Astronomy plays a major role in the scientific landscape of Namibia. Because of its excellent sky conditions, Namibia is home to ground-based observatories like the High Energy Spectroscopic System (H.E.S.S.), in operation since 2002. Located near the Gamsberg mountain, H.E.S.S. performs groundbreaking science by detecting very-high-energy gamma rays from astronomical objects. The fascinating stories behind many of them are featured regularly in the "Source of the Month", a blog-like format intended for the general public with more than 170 features to date. In addition to other online communication via social media, H.E.S.S. outreach activities have been covered locally, e.g. through 'open days' and guided tours on the site itself. An overview of the H.E.S.S. outreach activities are presented in this contribution, along with discussions relating to the current landscape of astronomy outreach and education in Namibia. There has also been significant activity in the country in recent months, whereby astronomy is being used to further sustainable development via human capacity-building. Finally, as we take into account the future prospects of radio astronomy in the country, momentum for a wider range of astrophysics research is clearly building — this presents a great opportunity for the astronomy community to come together to capitalise on this movement and support astronomy outreach, with the overarching aim to advance sustainable development in Namibia

Detection of new Extreme BL Lac objects with H.E.S.S. and Swift XRT

Extreme high synchrotron peaked blazars (EHBLs) are amongst the most powerful accelerators found in nature. Usually the synchrotron peak frequency of an EHBL is above 10$^{17}$ Hz, i.e., lies in the range of medium to hard X-rays making them ideal sources to study particle acceleration and radiative processes. EHBL objects are commonly observed at energies beyond several TeV, making them powerful probes of gamma-ray absorption in the intergalactic medium. During the last decade, several attempts have been made to increase the number of EHBL detected at TeV energies and probe their spectral characteristics. Here we report new detections of EHBLs in the TeV energy regime, each at a redshift of less than 0.2, by the High Energy Stereoscopic System (H.E.S.S.). Also, we report on X-ray observations of these EHBLs candidates with Swift-XRT. In conjunction with the very high energy observations, this allows us to probe the radiation mechanisms and the underlying particle acceleration processes

Evidence of 100 TeV γ-ray emission from HESS J1702-420 : a new PeVatron candidate

The identification of active PeVatrons, hadronic particle accelerators reaching the knee of the cosmic-ray spectrum (at the energy of few PeV), is crucial to understand the origin of cosmic rays in the Galaxy. In this context, we report on new H.E.S.S. observations of the PeVatron candidate HESS J1702-420, which bring evidence for the presence of γ-rays up to 100 TeV. This is the first time in the history of H.E.S.S. that photons with such high energy are observed. Remarkably, the new deep observations allowed the discovery of a new γ-ray source component, called HESS J1702-420A, that was previously hidden under the bulk emission traditionally associated with HESS J1702-420. This new object has a power-law spectral slope < 2 and a γ-ray spectrum that, extending with no sign of curvature up to 100 TeV, makes it an excellent candidate site for the presence of PeV-energy cosmic rays. This discovery brings new information to the ongoing debate on the nature of the unidentified source HESSJ1702-420, and on the origin of Galactic cosmic rays