Description of a New Halophilic Tiger Beetle in the Genus Eunota (Coleoptera, Cicindelidae, Cicindelini) Identified Using Morphology, Phylogenetics and Biogeography

Tiger beetles are a popular group of insects amongst amateur naturalists, and are well-represented in museum and private collections. New species descriptions plateaued in the 19th century, but there is a recent resurgence of discoveries as integrative taxonomy methods, guided by molecular systematics, uncover “cryptic” tiger beetle diversity. In this paper, we describe a new species using multiple data types. This new species, Eunota mecocheila Duran and Roman n. sp., is in the tribe Cicindelini, and is described from specimens collected in saline muddy ditches in northern Mexico. This species is closely related to E. circumpicta (LaFerté-Sénectère, 1841), but is separated based on morphological differences, geographic range, and genetic differentiation. Little is known about the biology or distribution of this species and it has only been collected from two sites in the state of Coahuila. Given the location of this new species, and its genetic divergence from its closest relative, E. circumpicta, we discuss the historical biogeography that may have led to isolation and speciation. The male and female dorsal, lateral and frontal habitus and the male aedeagus are shown

Cryptic diversity in the North American Dromochorus tiger beetles (Coleoptera: Carabidae: Cicindelinae): a congruence-based method for species discovery

A fundamental problem in biodiversity science is determining the number of species in any taxon, and there is a growing awareness that cryptic diversity contributes to this problem – even in well-studied groups. Discovering cryptic species requires several lines of evidence to elucidate congruent patterns across data-types, and distinguish unrecognized species. Tiger beetles are among the most well-studied insect groups; yet few new North American species have been described since the mid-20th century, suggesting that that the number of morphologically distinct species is reaching an asymptote. We explore the possibility that more species exist in the fauna as cryptic species, by analysing a broad geographic sample of all species in the genus Dromochorus. We employ a ‘taxonomic congruence’ approach, where we first generate species hypotheses from patterns of reciprocal monophyly across the mitochondrial and nuclear datasets, and test these hypotheses through congruence with population structure, morphological measures and ecological divergence. We find broad congruence that supports eight species of Dromochorus, more than doubling the known diversity. We also validate a previously ambiguous taxon, and re-describe previously named species. Lastly, we identify new diagnostic morphological characters, include an updated dichotomous key and provide updated natural history/ecological characteristics for the genus and individual species

Geographic Life History Differences Predict Genomic Divergence Better than Mitochondrial Barcodes or Phenotype

Species diversity can be inferred using multiple data types, however, results based on genetic data can be at odds with patterns of phenotypic variation. Tiger beetles of the Cicindelidia politula (LeConte, 1875) species complex have been taxonomically problematic due to extreme phenotypic variation within and between populations. To better understand the biology and taxonomy of this group, we used mtDNA genealogies and multilocus nuclear analyses of 34,921 SNPs to elucidate its evolutionary history and evaluate the validity of phenotypically circumscribed species and subspecies. Genetic analyses recovered two divergent species that are also ecologically distinct, based on adult life history. These patterns are incongruous with the phenotypic variation that informed prior taxonomy, and most subspecies were not supported as distinct evolutionary lineages. One of the nominal subspecies was found to be a cryptic species; consequently, we elevate C. p. laetipennis (Horn, 1913) to a full species. Although nuclear and mtDNA datasets recovered broadly similar evolutionary units, mito-nuclear discordance was more common than expected, being observed between nearly all geographically overlapping taxonomic pairs. Additionally, a pattern of ‘mitochondrial displacement’ was observed, where mitochondria from one species unidirectionally displace others. Overall, we found that geographically associated life history factors better predict genomic divergence than phenotype and mitochondrial genealogies, and consequently taxon identifications based on mtDNA (e.g., DNA barcodes) may be misleading

Force distributions in 3D granular assemblies: Effects of packing order and inter-particle friction

We present a systematic investigation of the distribution of normal forces at the boundaries of static packings of spheres. A new method for the efficient construction of large hexagonal-close-packed crystals is introduced and used to study the effect of spatial ordering on the distribution of forces. Under uniaxial compression we find that the form for the probability distribution of normal forces between particles does not depend strongly on crystallinity or inter-particle friction. In all cases the distribution decays exponentially at large forces and shows a plateau or possibly a small peak near the average force but does not tend to zero at small forces.Comment: 9 pages including 8 figure

Myxoma virus jumps species to the Iberian hare

The study of myxoma virus (MYXV) infections in the European rabbit (Oryctolagus cuniculus) has produced one of the most accepted host–pathogen evolutionary models. To date, myxomatosis has been limited to the European rabbit with sporadic reports in hares. However, reports of widespread mortalities in the Iberian hare (Lepus granatensis) with myxomatosis‐like clinical signs indicate a potential species jump has occurred. The presence of MYXV DNA was confirmed by PCR in 244 samples received from regional veterinary services, animal health laboratories, hunters or rangers over a 5‐month period. PCR analysis of 4 MYXV positive hare samples revealed a 2.8 kb insertion located within the M009 gene with respect to MYXV. The presence of this insertion was subsequently confirmed in 20 samples from 18 Spanish provinces. Sanger sequencing and subsequent analysis show that the insert contained 4 ORFs which are phylogenetically related to MYXV genes M060, M061, M064 and M065. The complete MYXV genome from hare tissue was sequenced using Ion torrent next‐generation technology and a summary of the data presented here. With the exception of the inserted region, the virus genome had no large scale modifications and 110 mutations with respect to the MYXV reference strain Lausanne were observed. The next phase in the evolution of MYXV has taken place as a host species jump from the European rabbit to the Iberian hare an occurrence which could have important effects on this naïve population.info:eu-repo/semantics/acceptedVersio

Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE):a randomised, open-label, multicentre, phase 3 trial

Background: Survival outcomes are poor for patients with metastatic urothelial carcinoma who receive standard, first-line, platinum-based chemotherapy. We assessed the overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab (a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma. Methods: DANUBE is an open-label, randomised, controlled, phase 3 trial in patients with untreated, unresectable, locally advanced or metastatic urothelial carcinoma, conducted at 224 academic research centres, hospitals, and oncology clinics in 23 countries. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned patients (1:1:1) to receive durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks; or standard-of-care chemotherapy (gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility) administered intravenously for up to six cycles. Randomisation was done through an interactive voice–web response system, with stratification by cisplatin eligibility, PD-L1 status, and presence or absence of liver metastases, lung metastases, or both. The coprimary endpoints were overall survival compared between the durvalumab monotherapy versus chemotherapy groups in the population of patients with high PD-L1 expression (the high PD-L1 population) and between the durvalumab plus tremelimumab versus chemotherapy groups in the intention-to-treat population (all randomly assigned patients). The study has completed enrolment and the final analysis of overall survival is reported. The trial is registered with ClinicalTrials.gov, NCT02516241, and the EU Clinical Trials Register, EudraCT number 2015-001633-24. Findings: Between Nov 24, 2015, and March 21, 2017, we randomly assigned 1032 patients to receive durvalumab (n=346), durvalumab plus tremelimumab (n=342), or chemotherapy (n=344). At data cutoff (Jan 27, 2020), median follow-up for survival was 41·2 months (IQR 37·9–43·2) for all patients. In the high PD-L1 population, median overall survival was 14·4 months (95% CI 10·4–17·3) in the durvalumab monotherapy group (n=209) versus 12·1 months (10·4–15·0) in the chemotherapy group (n=207; hazard ratio 0·89, 95% CI 0·71–1·11; p=0·30). In the intention-to-treat population, median overall survival was 15·1 months (13·1–18·0) in the durvalumab plus tremelimumab group versus 12·1 months (10·9–14·0) in the chemotherapy group (0·85, 95% CI 0·72–1·02; p=0·075). In the safety population, grade 3 or 4 treatment-related adverse events occurred in 47 (14%) of 345 patients in the durvalumab group, 93 (27%) of 340 patients in the durvalumab plus tremelimumab group, and in 188 (60%) of 313 patients in the chemotherapy group. The most common grade 3 or 4 treatment-related adverse event was increased lipase in the durvalumab group (seven [2%] of 345 patients) and in the durvalumab plus tremelimumab group (16 [5%] of 340 patients), and neutropenia in the chemotherapy group (66 [21%] of 313 patients). Serious treatment-related adverse events occurred in 30 (9%) of 345 patients in the durvalumab group, 78 (23%) of 340 patients in the durvalumab plus tremelimumab group, and 50 (16%) of 313 patients in the chemotherapy group. Deaths due to study drug toxicity were reported in two (1%) patients in the durvalumab group (acute hepatic failure and hepatitis), two (1%) patients in the durvalumab plus tremelimumab group (septic shock and pneumonitis), and one (<1%) patient in the chemotherapy group (acute kidney injury). Interpretation: This study did not meet either of its coprimary endpoints. Further research to identify the patients with previously untreated metastatic urothelial carcinoma who benefit from treatment with immune checkpoint inhibitors, either alone or in combination regimens, is warranted. Funding: AstraZeneca

p38γ and p38δ regulate postnatal cardiac metabolism through glycogen synthase 1

During the first weeks of postnatal heart development, cardiomyocytes undergo a major adaptive metabolic shift from glycolytic energy production to fatty acid oxidation. This metabolic change is contemporaneous to the up-regulation and activation of the p38γ and p38δ stress-activated protein kinases in the heart. We demonstrate that p38γ/δ contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38γ/δ activation in cardiomyocytes of newborn mice results in an early GYS1 phosphorylation and inhibition of cardiac glycogen production, triggering an early metabolic shift that induces a deficit in cardiomyocyte fuel supply, leading to whole-body metabolic deregulation and maladaptive cardiac pathogenesis. Notably, the adverse effects of forced premature cardiac p38γ/δ activation in neonate mice are prevented by maternal diet supplementation of fatty acids during pregnancy and lactation. These results suggest that diet interventions have a potential for treating human cardiac genetic diseases that affect heart metabolism.G.S. is a YIP EMBO member. B.G.T. was a fellow of the FPI Severo Ochoa CNIC program (SVP-2013-067639) and currently is funded by the AHA-CHF (AHA award number: 818798). V.M.R. is a FPI fellow (BES-2014-069332) and A.M.S. is a fellow of the FPI Severo Ochoa CNIC program (BES-2016-077635). This work was funded by the following grants: to G.S.: funding from the EFSD/Lilly European Diabetes Research Programme Dr Sabio, from Spanish Ministry of Science, Innovation and Universities (MINECO-FEDER SAF2016-79126-R and PID2019-104399RB-I00), Comunidad de Madrid (IMMUNOTHERCAN-CM S2010/BMD-2326 and B2017/BMD-3733) and Fundación Jesús Serra; to P.A.: Ayudas para apoyar grupos de investigación del sistema Universitario Vasco (IT971-16 to P.A.), MCIU/AEI/FEDER, funding from Spanish Ministry of Science, Innovation and Universities (RTI2018-095134-B-100); Excellence Network Grant from MICIU/AEI (SAF2016-81975-REDT and 2018-PN188) to PA and GS; to J.V.: funding from Spanish Ministry of Science, Innovation and Universities (PGC2018-097019-B-I00), the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria grant PRB3 (PT17/0019/0003- ISCIII-SGEFI / ERDF, ProteoRed), and “la Caixa” Banking Foundation (project code HR17-00247); to J.P.B.: funding from Spanish Ministry of Science, Innovation and Universities (PID2019-105699RB-I00, RED2018‐102576‐T) and Escalera de Excelencia (CLU-2017-03); to J.A.E.: funding from Spanish Ministry of Science, Innovation and Universities MINECO (RED2018-102576-T, RTI2018-099357-B-I00), CIBERFES (CB16/10/00282), and HFSP (RGP0016/2018). RAP (XPC/BBV1602 and MIN/RYC1102). The CNIC is supported by the Ministry of Science, Innovation and Universities and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A View of Tropical Cyclones from Above: The Tropical Cyclone Intensity Experiment

Tropical cyclone (TC) outflow and its relationship to TC intensity change and structure were investigated in the Office of Naval Research Tropical Cyclone Intensity (TCI) field program during 2015 using dropsondes deployed from the innovative new High-Definition Sounding System (HDSS) and remotely sensed observations from the Hurricane Imaging Radiometer (HIRAD), both on board the NASA WB-57 that flew in the lower stratosphere. Three noteworthy hurricanes were intensively observed with unprecedented horizontal resolution: Joaquin in the Atlantic and Marty and Patricia in the eastern North Pacific. Nearly 800 dropsondes were deployed from the WB-57 flight level of ∼60,000 ft (∼18 km), recording atmospheric conditions from the lower stratosphere to the surface, while HIRAD measured the surface winds in a 50-km-wide swath with a horizontal resolution of 2 km. Dropsonde transects with 4–10-km spacing through the inner cores of Hurricanes Patricia, Joaquin, and Marty depict the large horizontal and vertical gradients in winds and thermodynamic properties. An innovative technique utilizing GPS positions of the HDSS reveals the vortex tilt in detail not possible before. In four TCI flights over Joaquin, systematic measurements of a major hurricane’s outflow layer were made at high spatial resolution for the first time. Dropsondes deployed at 4-km intervals as the WB-57 flew over the center of Hurricane Patricia reveal in unprecedented detail the inner-core structure and upper-tropospheric outflow associated with this historic hurricane. Analyses and numerical modeling studies are in progress to understand and predict the complex factors that influenced Joaquin’s and Patricia’s unusual intensity changes

A correlative biomarker study and integrative prognostic model in chemotherapy-naïve metastatic castration-resistant prostate cancer treated with enzalutamide

There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical-molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort. Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p < 0.0001), rad-PFS (4.5 vs. 27.6 m; p < 0.0001), and OS (12.7 vs. 38.1 m; p < 0.0001). The clinical prognostic model developed in PREVAIL was validated (C-Index 0.70) and the addition of plasma AR (C-Index 0.79; p < 0.001) increased its prognostic ability. We generated a parsimonious model including alkaline phosphatase (ALP); PSA and AR gain (C-index 0.78) that was validated in an independent cohort. TMPRSS2-ERG detection did not correlate with differential activity of enzalutamide in first-line mCRPC. However, we observed that CTCs and plasma AR gain were the most relevant biomarkers

The Reverse Brazil Nut Problem: Competition between Percolation and Condensation

In the Brazil nut problem (BNP), hard spheres with larger diameters rise to the top. There are various explanations (percolation, reorganization, convection), but a broad understanding or control of this effect is by no means acheived. A theory is presented for the crossover from the BNP to the reverse Brazil nut problem (RBNP) based on a competition between the percolation effect and the condensation of hard spheres. The crossover condition is determined, and the theoretical predictions are compared to Molecular Dynamics simulations in two and three dimensions.Comment: 9 pages which includes 7 figure