Calicioid lichens and fungi in amber : Tracing extant lineages back to the Paleogene

Calicioid lichens and fungi are a polyphyletic grouping of tiny ascomycetes that accumulate a persistent spore mass (mazaedium) on top of their usually well-stalked ascomata ('mazaediate fungi'). In addition to extant forms, six fossils of the group were previously known from European Paleogene amber. Here we report nine new fossils and analyze the preserved features of all fossils to assess their applicability for dating molecular phylogenies. Many fossils are extremely well preserved, allowing detailed comparisons with modern taxa. SEM investigation reveals that even fine details of ascospore wall ultrastructure correspond to those seen in extant specimens. All fossils can confidently be assigned to modern genera: three to Calicium (Caliciaceae, Lecanoromycetes), five to Chaenotheca (Coniocybaceae, Coniocybomycetes), six to Chaenothecopsis (Mycocaliciaceae, Eurotiales), and one to Phaeocalicium (Mycocaliciaceae, Eurotiales). Several Calicium and Chaenotheca fossils are assignable to specific lineages within their genera, while the Chaenothecopsis fossils demonstrate the extent of intraspecific variation within one such lineage. Some features in the morphology of Chaenotheca succina nov. sp. seem to be ancestral as they have not been reported from modern species of the genus. (C) 2018 Elsevier Masson SAS. All rights reserved.Peer reviewe

Prognostic ability of the German version of the STarT Back tool: analysis of 12-month follow-up data from a randomized controlled trial

Background: Stratified care is an up-to-date treatment approach suggested for patients with back pain in several guidelines. A comprehensively studied stratification instrument is the STarT Back Tool (SBT). It was developed to stratify patients with back pain into three subgroups, according to their risk of persistent disabling symptoms. The primary aim was to analyse the disability differences in patients with back pain 12 months after inclusion according to the subgroups determined at baseline using the German version of the SBT (STarT-G). Moreover, the potential to improve prognosis for disability by adding further predictor variables, an analysis for differences in pain intensity according to the STarT-Classification, and discriminative ability were investigated. Methods: Data from the control group of a randomized controlled trial were analysed. Trial participants were members of a private medical insurance with a minimum age of 18 and indicated as having persistent back pain. Measurements were made for the risk of back pain chronification using the STarT-G, disability (as primary outcome) and back pain intensity with the Chronic Pain Grade Scale (CPGS), health-related quality of life with the SF-12, psychological distress with the Patient Health Questionnaire-4 (PHQ-4) and physical activity. Analysis of variance (ANOVA), multiple linear regression, and area under the curve (AUC) analysis were conducted. Results: The mean age of the 294 participants was 53.5 (SD 8.7) years, and 38% were female. The ANOVA for disability and pain showed significant differences (p < 0.01) among the risk groups at 12 months. Post hoc Tukey tests revealed significant differences among all three risk groups for every comparison for both outcomes. AUC for STarT-G’s ability to discriminate reference standard ‘cases’ for chronic pain status at 12 months was 0.79. A prognostic model including the STarT-Classification, the variables global health, and disability at baseline explained 45% of the variance in disability at 12 months. Conclusions: Disability differences in patients with back pain after a period of 12 months are in accordance with the subgroups determined using the STarT-G at baseline. Results should be confirmed in a study developed with the primary aim to investigate those differences

Influence of the Stability of a Fused Protein and Its Distance to the Amyloidogenic Segment on Fibril Formation

Conversion of native proteins into amyloid fibrils is irreversible and therefore it is difficult to study the interdependence of conformational stability and fibrillation by thermodynamic analyses. Here we approached this problem by fusing amyloidogenic poly-alanine segments derived from the N-terminal domain of the nuclear poly (A) binding protein PABPN1 with a well studied, reversibly unfolding protein, CspB from Bacillus subtilis. Earlier studies had indicated that CspB could maintain its folded structure in fibrils, when it was separated from the amyloidogenic segment by a long linker. When CspB is directly fused with the amyloidogenic segment, it unfolds because its N-terminal chain region becomes integrated into the fibrillar core, as shown by protease mapping experiments. Spacers of either 3 or 16 residues between CspB and the amyloidogenic segment were not sufficient to prevent this loss of CspB structure. Since the low thermodynamic stability of CspB (ΔGD = 12.4 kJ/mol) might be responsible for unfolding and integration of CspB into fibrils, fusions with a CspB mutant with enhanced thermodynamic stability (ΔGD = 26.9 kJ/mol) were studied. This strongly stabilized CspB remained folded and prevented fibril formation in all fusions. Our data show that the conformational stability of a linked, independently structured protein domain can control fibril formation

Long-term multi-wavelength study of 1ES 0647+250

The BL Lac object 1ES 0647+250 is one of the few distant $\gamma$-ray emitting blazars detected at very high energies (VHE, $\gtrsim$100 GeV) during a non-flaring state. It was detected with the MAGIC telescopes during its low activity in the years 2009-2011, as well as during three flaring activities in the years 2014, 2019 and 2020, with the highest VHE flux in the latter epoch. An extensive multi-instrument data set was collected within several coordinated observing campaigns throughout these years. We aim to characterise the long-term multi-band flux variability of 1ES 0647+250, as well as its broadband spectral energy distribution (SED) during four distinct activity states selected in four different epochs, in order to constrain the physical parameters of the blazar emission region under certain assumptions. We evaluate the variability and correlation of the emission in the different energy bands with the fractional variability and the Z-transformed Discrete Correlation Function, as well as its spectral evolution in X-rays and $\gamma$ rays. Owing to the controversy in the redshift measurements of 1ES 0647+250 reported in the literature, we also estimate its distance in an indirect manner through the comparison of the GeV and TeV spectra from simultaneous observations with Fermi-LAT and MAGIC during the strongest flaring activity detected to date. Moreover, we interpret the SEDs from the four distinct activity states within the framework of one-component and two-component leptonic models, proposing specific scenarios that are able to reproduce the available multi-instrument data.Comment: 20 pages, 7 figures. Accepted in A&A. Corresponding authors: Jorge Otero-Santos; Daniel Morcuende; Vandad Fallah Ramazani; Daniela Dorner; David Paneque (mailto: [email protected]

Investigating the blazar TXS 0506+056 through sharp multi-wavelength eyes during 2017-2019

The blazar TXS 0506+056 got into the spotlight of the astrophysical community in September 2017, when a high-energy neutrino detected by IceCube (IceCube-170922A) was associated at the 3 $\sigma$ level to a $\gamma$-ray flare from this source. This multi-messenger photon-neutrino association remains, as per today, the most significant one ever observed. TXS 0506+056 was a poorly studied object before the IceCube-170922A event. To better characterize its broad-band emission, we organized a multi-wavelength campaign lasting 16 months (November 2017 to February 2019), covering the radio-band (Mets\"ahovi, OVRO), the optical/UV (ASAS-SN, KVA, REM, Swift/UVOT), the X-rays (Swift/XRT, NuSTAR), the high-energy $\gamma$ rays (Fermi/LAT) and the very-high-energy (VHE) $\gamma$ rays (MAGIC). In $\gamma$ rays, the behaviour of the source was significantly different from the 2017 one: MAGIC observations show the presence of flaring activity during December 2018, while the source only shows an excess at the 4$\sigma$ level during the rest of the campaign (74 hours of accumulated exposure); Fermi/LAT observations show several short (days-to-week timescale) flares, different from the long-term brightening of 2017. No significant flares are detected at lower energies. The radio light curve shows an increasing flux trend, not seen in other wavelengths. We model the multi-wavelength spectral energy distributions in a lepto-hadronic scenario, in which the hadronic emission emerges as Bethe-Heitler and pion-decay cascade in the X-rays and VHE $\gamma$ rays. According to the model presented here, the December 2018 $\gamma$-ray flare was connected to a neutrino emission that was too brief and not bright enough to be detected by current neutrino instruments.Comment: 18 pages, 6 figures; in press in Ap

Patient-derived xenograft (PDX) models in basic and translational breast cancer research

Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward "credentialing" of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research

The variability patterns of the TeV blazar PG 1553 + 113 from a decade of MAGIC and multiband observations

PG 1553 + 113 is one of the few blazars with a convincing quasi-periodic emission in the gamma-ray band. The source is also a very high energy (VHE; >100 GeV) gamma-ray emitter. To better understand its properties and identify the underlying physical processes driving its variability, the MAGIC Collaboration initiated a multiyear, multiwavelength monitoring campaign in 2015 involving the OVRO 40-m and Medicina radio telescopes, REM, KVA, and the MAGIC telescopes, Swift and Fermi satellites, and the WEBT network. The analysis presented in this paper uses data until 2017 and focuses on the characterization of the variability. The gamma-ray data show a (hint of a) periodic signal compatible with literature, but the X-ray and VHE gamma-ray data do not show statistical evidence for a periodic signal. In other bands, the data are compatible with the gamma-ray period, but with a relatively high p-value. The complex connection between the low- and high-energy emission and the non-monochromatic modulation and changes in flux suggests that a simple one-zone model is unable to explain all the variability. Instead, a model including a periodic component along with multiple emission zones is required

Southern African Large Telescope Spectroscopy of BL Lacs for the CTA project

In the last two decades, very-high-energy gamma-ray astronomy has reached maturity: over 200 sources have been detected, both Galactic and extragalactic, by ground-based experiments. At present, Active Galactic Nuclei (AGN) make up about 40% of the more than 200 sources detected at very high energies with ground-based telescopes, the majority of which are blazars, i.e. their jets are closely aligned with the line of sight to Earth and three quarters of which are classified as high-frequency peaked BL Lac objects. One challenge to studies of the cosmological evolution of BL Lacs is the difficulty of obtaining redshifts from their nearly featureless, continuum-dominated spectra. It is expected that a significant fraction of the AGN to be detected with the future Cherenkov Telescope Array (CTA) observatory will have no spectroscopic redshifts, compromising the reliability of BL Lac population studies, particularly of their cosmic evolution. We started an effort in 2019 to measure the redshifts of a large fraction of the AGN that are likely to be detected with CTA, using the Southern African Large Telescope (SALT). In this contribution, we present two results from an on-going SALT program focused on the determination of BL Lac object redshifts that will be relevant for the CTA observatory

Licht-induzierte molekulare Struktur Eine experimentelle Untersuchung

Available from TIB Hannover: RN 5339(210) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Optimized Variants of the Cold Shock Protein from in Vitro Selection: Structural Basis of Their High Thermostability

The bacterial cold shock proteins (Csp) are widely used as models for the experimental and computational analysis of protein stability. In a previous study, in vitro evolution was employed to identify strongly stabilizing mutations in Bs-CspB from Bacillus subtilis. The best variant found by this approach contained the mutations M1R, E3K and K65I, which raised the midpoint of thermal unfolding of Bs-CspB from 53.8 degrees C to 83.7 degrees C, and increased the Gibbs free energy of stabilization by 20.9 kJ mol(-1). Another selected variant with the two mutations A46K and S48R was stabilized by 11.1 kJ mol(-1). To elucidate the molecular basis of these stabilizations, we determined the crystal structures of these two Bs-CspB variants. The mutated residues are generally well ordered and provide additional stabilizing interactions, such as charge interactions, additional hydrogen bonds and improved side-chain packing. Several mutations improve the electrostatic interactions, either by the removal of unfavorable charges (E3K) or by compensating their destabilizing interactions (A46K, S48R). The stabilizing mutations are clustered at a contiguous surface area of Bs-CspB, which apparently is critically important for the stability of the beta-barrel structure but not well optimized in the wild-type protein