Joint H.E.S.S. and Fermi-LAT analysis of the region around PSR J1813-1749

HESS J1813-178 is one of the brightest sources detected during the first HESS Galactic Plane survey. The compact source, also detected by MAGIC, is believed to be a pulsar wind nebula powered by one of the most powerful pulsars known in the Galaxy, PSR J1813-1749 with a spin-down luminosity of $\dot{\mathrm{E}} = 5.6 \cdot 10^{37}\,\mathrm{erg}\,\mathrm{s}^{-1}$. With its extreme physical properties, as well as the pulsar's young age of 5.6 kyrs, the $\gamma$-rays detected in this region allow us to study the evolution of a highly atypical system. Previous studies of the region in the GeV energy range show emission extended beyond the size of the compact H.E.S.S. source. Using the archival H.E.S.S. data with improved background methods, we perform a detailed morphological and spectral analysis of the region. Additionally to the compact, bright emission component, we find significantly extended emission, whose position is coincident with HESS J1813-178. We reanalyse the region in GeV and derive a joint-model in order to find a continuous description of the emission in the region from GeV to TeV. Using the results derived in this analysis, as well as X-ray and radio data of the region, we perform multi-wavelength spectral modeling. Possible hadronic or leptonic origins of the $\gamma$-ray emission are investigated, and the diffusion parameters necessary to explain the extended emission are examined.Comment: 8 pages, 4 figures, 1 table, In proceedings of ICRC202

Taking nature into lab: biomineralization by heavy metal-resistant streptomycetes in soil

Biomineralization by heavy metal-resistant streptomycetes was tested to evaluate the potential influence on metal mobilities in soil. Thus, we designed an experiment adopting conditions from classical laboratory methods to natural conditions prevailing in metal-rich soils with media spiked with heavy metals, soil agar, and nutrientenriched or unamended soil incubated with the bacteria. As a result, all strains were able to form struvite minerals (MgNH4PO4 6H2O) on tryptic soy broth (TSB)-media supplemented with AlCl3, MnCl2 and CuSO4, as well as on soil agar. Some strains additionally formed struvite on nutrient-enriched contaminated and control soil, as well as on metal contaminated soil without addition of media components. In contrast, switzerite (Mn3(PO4)2 7H2O) was exclusively formed on minimal media spiked with MnCl2 by four heavy metal-resistant strains, and on nutrient-enriched control soil by one strain. Hydrated nickel hydrogen phosphate was only crystallized on complex media supplemented with NiSO4 by most strains. Thus, mineralization is a dominant property of streptomycetes, with different processes likely to occur under laboratory conditions and sub-natural to natural conditions. This new understanding might have implications for our understanding of biological metal resistance mechanisms. We assume that biogeochemical cycles, nutrient storage and metal resistance might be affected by formation and re-solubilization of minerals like struvite in soil at microscale

Ancestors of domestic cats in Neolithic Central Europe : isotopic evidence of a synanthropic diet

Cat remains from Poland dated to 4,200 to 2,300 y BCE are currently the earliest evidence for the migration of the Near Eastern cat (NE cat), the ancestor of domestic cats, into Central Europe. This early immigration preceded the known establishment of housecat populations in the region by around 3,000 y. One hypothesis assumed that NE cats followed the migration of early farmers as synanthropes. In this study, we analyze the stable isotopes in six samples of Late Neolithic NE cat bones and further 34 of the associated fauna, including the European wildcat. We approximate the diet and trophic ecology of Late Neolithic felids in a broad context of contemporary wild and domestic animals and humans. In addition, we compared the ecology of Late Neolithic NE cats with the earliest domestic cats known from the territory of Poland, dating to the Roman Period. Our results reveal that human agricultural activity during the Late Neolithic had already impacted the isotopic signature of rodents in the ecosystem. These synanthropic pests constituted a significant proportion of the NE cat’s diet. Our interpretation is that Late Neolithic NE cats were opportunistic synanthropes, most probably free-living individuals (i.e., not directly relying on a human food supply). We explore niche partitioning between studied NE cats and the contemporary native European wildcats. We find only minor differences between the isotopic ecology of both these taxa. We conclude that, after the appearance of the NE cat, both felid taxa shared the ecological niches

MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer

Prostate cancer (PCa) shows strong dependence on the androgen receptor (AR) pathway. Here, we show that squalene epoxidase (SQLE), an enzyme of the cholesterol biosynthesis pathway, is overexpressed in advanced PCa and its expression correlates with poor survival. SQLE expression is controlled by micro-RNA 205 (miR-205), which is significantly downregulated in advanced PCa. Restoration of miR-205 expression or competitive inhibition of SQLE led to inhibition of de novo cholesterol biosynthesis. Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Inhibition of SQLE with the FDA approved antifungal drug terbinafine also efficiently blocked orthotopic tumour growth in mice. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa

Seamless Gene Tagging by Endonuclease-Driven Homologous Recombination

Gene tagging facilitates systematic genomic and proteomic analyses but chromosomal tagging typically disrupts gene regulatory sequences. Here we describe a seamless gene tagging approach that preserves endogenous gene regulation and is potentially applicable in any species with efficient DNA double-strand break repair by homologous recombination. We implement seamless tagging in Saccharomyces cerevisiae and demonstrate its application for protein tagging while preserving simultaneously upstream and downstream gene regulatory elements. Seamless tagging is compatible with high-throughput strain construction using synthetic genetic arrays (SGA), enables functional analysis of transcription antisense to open reading frames and should facilitate systematic and minimally-invasive analysis of gene functions

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Stromal-epithelial interaction induces GALNT14 in prostate carcinoma cells

IntroductionCell-cell communication is an important process in healthy tissue but also gains enhanced attention regarding pathological tissue. To date, the tumor microenvironment is gradually brought into focus when studying tumorigenesis. In the prostate gland, stromal and epithelial cells greatly interact to maintain homeostasis or tissue integrity. This study focuses on an indirect communication via soluble factors.MethodsTo investigate the cell-cell interaction via soluble factors, the prostate carcinoma cell line LNCaP and the stromal primary cells p21 were co-cultured without direct contact and RNA was isolated at defined time points. Differences in gene expression were finally analyzed by RNA sequencing.ResultsRNA sequencing revealed a time-depending differential expression profile. Selected factors were subsequently characterized at molecular level and analyzed in human prostate tissue of different developmental stages as well as pathology. GALNT14 was one of the highest induced co-culture-specific genes in LNCaP cells. Detection in healthy tissue and BPH revealed an age-dependent decrease in GALNT14 expression. Moreover, in prostate carcinoma, GALNT14 expression heavily varied independent of the Gleason score.ConclusionOverall, this work provides a basis for further studies related to paracrine stromal-epithelial interaction in prostate carcinoma and highlights the importance of GALNT14

Browsers, grazers or mix-feeders? Study of the diet of extinct Pleistocene Eurasian forest rhinoceros Stephanorhinus kirchbergensis (J¨ager, 1839) and woolly rhinoceros Coelodonta antiquitatis (Blumenbach, 1799)

The wooly rhinoceros (Coelodonta antiquitatis) and forest rhinoceros (Stephanorhinus kirchbergensis) were prominent representatives of the Middle and Late Pleistocene glacial and interglacial faunas of Eurasia. Their diet has traditionally been inferred on functional morphology of the dentition and skull. In rare cases, food remains are preserved in the fossas of the teeth or as gut content. New approaches to infer diet include the study of isotopes and mesowear. Here we apply all four methods to infer the diet of these emblematic rhinoceros’ species and compare the food actually taken with the food available, as indicated by independent botanical data from the localities where the rhinoceros’ fossils were found: Gorz´ow Wielkopolski (Eemian) and Starunia (Middle Vistulian) as well as analysis of literature data. We also made inferences on the season of death of these individuals. Our results indicate that the woolly rhino in both Europe and Asia (Siberia) was mainly a grazer, although at different times of the year and depending on the region its diet was also supplemented by leaves of shrubs and trees. According to the results of isotope studies, there were important individual variations. The data show a clear seasonal variation in the isotope composition of this rhino’s diet. In contrast, Stephanorhinus kirchbergensis was a browser, though its diet included low-growing vegetation. Its habitat consisted of various types of forests, from riparian to deciduous and mixed forests, and open areas. The diet of this species consisted of selected items of vegetation, also including plants growing near both flowing and standing waters. The food remains from the fossae of the teeth indicated flexible browsing, confirming the previous interpretations based on functional morphology and stable isotopes. Long-term data from mesowear and microwear across a wider range of S. kirchbergensis fossils indicate a more mixed diet with a browsing component. The different diets of both of rhinoceros reflect not only the different habitats, but also climate changes that occurred during the Late Pleistocene