A bovine model of a respiratory Parachlamydia acanthamoebae infection.

The aim of this study was to evaluate the pathogenicity of Parachlamydia (P.) acanthamoebae as a potential agent of lower respiratory tract disease in a bovine model of induced lung infection. Intrabronchial inoculation with P. acanthamoebae was performed in healthy calves aged 2-3 months using two challenge doses: 10(8) and 10(10) bacteria per animal. Controls received 10(8) heat-inactivated bacteria. Challenge with 10(8) viable Parachlamydia resulted in a mild degree of general indisposition, whereas 10(10) bacteria induced a more severe respiratory illness becoming apparent 1-2 days post inoculation (dpi), affecting 9/9 (100%) animals and lasting for 6 days. The extent of macroscopic pulmonary lesions was as high as 6.6 (6.0)% [median (range)] of lung tissue at 2-4 dpi and correlated with parachlamydial genomic copy numbers detected by PCR, and with bacterial load estimated by immunohistochemistry in lung tissue. Clinical outcome, acute phase reactants, pathological findings and bacterial load exhibited an initial dose-dependent effect on severity. Animals fully recovered from clinical signs of respiratory disease within 5 days. The bovine lung was shown to be moderately susceptible to P. acanthamoebae, exhibiting a transient pneumonic inflammation after intrabronchial challenge. Further studies are warranted to determine the precise pathophysiologic pathways of host-pathogen interaction

Sulfur bacteria promote dissolution of authigenic carbonates at marine methane seeps

Carbonate rocks at marine methane seeps are commonly colonized by sulfur-oxidizing bacteria that co-occur with etch pits that suggest active dissolution. We show that sulfur-oxidizing bacteria are abundant on the surface of an exemplar seep carbonate collected from Del Mar East Methane Seep Field, USA. We then used bioreactors containing aragonite mineral coupons that simulate certain seep conditions to investigate plausible in situ rates of carbonate dissolution associated with sulfur-oxidizing bacteria. Bioreactors inoculated with a sulfur-oxidizing bacterial strain, Celeribacter baekdonensis LH4, growing on aragonite coupons induced dissolution rates in sulfidic, heterotrophic, and abiotic conditions of 1773.97 (±324.35), 152.81 (±123.27), and 272.99 (±249.96) μmol CaCO_3 • cm^−2 • yr^−1, respectively. Steep gradients in pH were also measured within carbonate-attached biofilms using pH-sensitive fluorophores. Together, these results show that the production of acidic microenvironments in biofilms of sulfur-oxidizing bacteria are capable of dissolving carbonate rocks, even under well-buffered marine conditions. Our results support the hypothesis that authigenic carbonate rock dissolution driven by lithotrophic sulfur-oxidation constitutes a previously unknown carbon flux from the rock reservoir to the ocean and atmosphere.https://www.nature.com/articles/s41396-021-00903-

Understanding complexity in the HIF signaling pathway using systems biology and mathematical modeling

Hypoxia is a common micro-environmental stress which is experienced by cells during a range of physiologic and pathophysiologic processes. The identification of the hypoxia-inducible factor (HIF) as the master regulator of the transcriptional response to hypoxia transformed our understanding of the mechanism underpinning the hypoxic response at the molecular level and identified HIF as a potentially important new therapeutic target. It has recently become clear that multiple levels of regulatory control exert influence on the HIF pathway giving the response a complex and dynamic activity profile. These include positive and negative feedback loops within the HIF pathway as well as multiple levels of crosstalk with other signaling pathways. The emerging model reflects a multi-level regulatory network that affects multiple aspects of the physiologic response to hypoxia including proliferation, apoptosis, and differentiation. Understanding the interplay between the molecular mechanisms involved in the dynamic regulation of the HIF pathway at a systems level is critically important in defining new appropriate therapeutic targets for human diseases including ischemia, cancer, and chronic inflammation. Here, we review our current knowledge of the regulatory circuits which exert influence over the HIF response and give examples of in silico model-based predictions of the dynamic behaviour of this system

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Nachrechnungen zu den Versuchen L5 und L2 der ACE Phase C Testserie

Available from FIZ Karlsruhe / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Thermodynamische Stoffdaten fuer chemische Gleichgewichtsrechnungen bei der Schmelze-Beton-Wechselwirkung 2. Zwischenbericht

Available from FIZ Karlsruhe / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Neue Ergebnisse zur Spaltproduktfreisetzung aus dem Kern und Reaktorgebaeude bei Unfaellen

SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman