Crystal structure of N,N,N-tris-[(1,3-benzo-thia-zol-2-yl)meth-yl]amine.

The title compound, C24H18N4S3, exhibits three near planar benzo-thia-zole systems in a pseudo-C 3 conformation. The dihedral angles between the planes of the benzo-thia-zole groups range from 112.56 (4) to 124.68 (4)° In the crystal, mol-ecules are connected to each other through three short C-H⋯N contacts, forming an infinite chain along [100]. The molecules are also linked by π-π interactions with each of the three five-membered thiazole rings. [inter-centroid distance range: 3.614 (1)-4.074 (1) Å, inter-planar distance range: 3.4806 (17)-3.6902 (15) Å, slippage range: 0.759 (3)-1.887 (3) Å]

Intercolony variation in reproductive skipping in the African penguin

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data underlying this article are available in the Dryad digital repository: https://doi.org/10.5061/dryad.0rxwdbs3z (Leith et al., 2022).In long-lived species, reproductive skipping is a common strategy whereby sexually mature animals skip a breeding season, potentially reducing population growth. This may be an adaptive decision to protect survival, or a non-adaptive decision driven by individual-specific constraints. Understanding the presence and drivers of reproductive skipping behavior can be important for effective population management, yet in many species such as the endangered African penguin (Spheniscus demersus), these factors remain unknown. This study uses multistate mark-recapture methods to estimate African penguin survival and breeding probabilities at two colonies between 2013 and 2020. Overall, survival (mean ± SE) was higher at Stony Point (0.82 ± 0.01) than at Robben Island (0.77 ± 0.02). Inter-colony differences were linked to food availability; under decreasing sardine (Sardinops sagax) abundance, survival decreased at Robben Island and increased at Stony Point. Additionally, reproductive skipping was evident across both colonies; at Robben Island the probability of a breeder becoming a nonbreeder was ~0.22, versus ~0.1 at Stony Point. Penguins skipping reproduction had a lower probability of future breeding than breeding individuals; this lack of adaptive benefit suggests reproductive skipping is driven by individual-specific constraints. Lower survival and breeding propensity at Robben Island places this colony in greater need of conservation action. However, further research on the drivers of inter-colony differences is needed.Association of Zoos and AquariumsBristol Zoological SocietyDepartment of Forestry, Fisheries, and the EnvironmentEarthwatch InstitutePew Charitable TrustsLeiden Conservation FoundationSANCCOBSan Diego Zoo Wildlife Allianc

Nanoparticles and thin films of silver from complexes of derivatives of N-(diisopropylthiophosphoryl) thioureas

The derivatives of JV-(diisopropylthiophosphoryl)thiourea RC(S)NHP(S)(OiPr)2 (R = C5H11N, C5H6N2 or C10H7NH 2) followed by their complexation with silver are reported. All complexes are decomposed in hot hexadecylamine (HDA) to give HDA-capped silver nanoparticles. The absorption spectra of the HDA-capped silver nanoparticles exhibit surface plasmon resonance (SPR) absorption in the 400-420 nm region. Transmission electron microscopy (TEM) images of all particles are close to spherical in shape; with sizes ranging from 17 to 20 nm. The X-ray diffraction (XRD) patterns of the silver nanoparticles obtained from all three complexes could be indexed to face centered cubic silver. Scanning electron microscopy (SEM) image confirmed the spherical shape of the particles. The silver complex of 1-naphthylamine was also used to deposit thin films of silver by the aerosol-assisted chemical vapor deposition (AACVD). © 2009 American Chemical Society

The influence of helium-induced defects on the migration of strontium implanted into SiC above critical amorphization temperature

The presence of radiation-induced defects and the high temperature of implantation are breeding grounds for helium (He) to accumulate and form He-induced defects (bubbles, blisters, craters, and cavities) in silicon carbide (SiC). In this work, the influence of He-induced defects on the migration of strontium (Sr) implanted into SiC was investigated. Sr-ions of 360 keV were implanted into polycrystalline SiC to a fluence of 2 × 1016 Sr-ions/cm2 at 600°C (Sr-SiC). Some of the Sr-SiC samples were then co-implanted with He-ions of 21.5 keV to a fluence of 1 × 1017 He-ions/cm2 at 350°C (Sr + He-SiC). The Sr-SiC and Sr + He-SiC samples were annealed for 5 h at 1,000°C. The as-implanted and annealed samples were characterized by Raman spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), transmission electron microscopy (TEM), and Rutherford backscattered spectrometry (RBS). Implantation of Sr retained some defects in SiC, while co-implantation of He resulted in the formation of He-bubbles, blisters, and craters (exfoliated blisters). Blisters close to the critical height and size were the first to exfoliate after annealing. He-bubbles grew larger after annealing owing to the capture of more vacancies. In the co-implanted samples, Sr was located in three regions: the crystalline region (near the surface), the bubble region (where the projected range of Sr was located), and the damage region toward the bulk. Annealing the Sr + He-SiC caused the migration of Sr towards the bulk, while no migration was observed in the Sr-SiC samples. The migration was governed by “vacancy migration driven by strain fileds.

Structural Insights into the Quinolone Resistance Mechanism of Mycobacterium tuberculosis DNA Gyrase

Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP) is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA

Mycobacterial dihydrofolate reductase inhibitors identified using chemogenomic methods and in vitro validation.

The lack of success in target-based screening approaches to the discovery of antibacterial agents has led to reemergence of phenotypic screening as a successful approach of identifying bioactive, antibacterial compounds. A challenge though with this route is then to identify the molecular target(s) and mechanism of action of the hits. This target identification, or deorphanization step, is often essential in further optimization and validation studies. Direct experimental identification of the molecular target of a screening hit is often complex, precisely because the properties and specificity of the hit are not yet optimized against that target, and so many false positives are often obtained. An alternative is to use computational, predictive, approaches to hypothesize a mechanism of action, which can then be validated in a more directed and efficient manner. Specifically here we present experimental validation of an in silico prediction from a large-scale screen performed against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis. The two potent anti-tubercular compounds studied in this case, belonging to the tetrahydro-1,3,5-triazin-2-amine (THT) family, were predicted and confirmed to be an inhibitor of dihydrofolate reductase (DHFR), a known essential Mtb gene, and already clinically validated as a drug target. Given the large number of similar screening data sets shared amongst the community, this in vitro validation of these target predictions gives weight to computational approaches to establish the mechanism of action (MoA) of novel screening hit

Genome-Scale Identification Method Applied to Find Cryptic Aminoglycoside Resistance Genes in Pseudomonas aeruginosa

BACKGROUND:The ability of bacteria to rapidly evolve resistance to antibiotics is a critical public health problem. Resistance leads to increased disease severity and death rates, as well as imposes pressure towards the discovery and development of new antibiotic therapies. Improving understanding of the evolution and genetic basis of resistance is a fundamental goal in the field of microbiology. RESULTS:We have applied a new genomic method, Scalar Analysis of Library Enrichments (SCALEs), to identify genomic regions that, given increased copy number, may lead to aminoglycoside resistance in Pseudomonas aeruginosa at the genome scale. We report the result of selections on highly representative genomic libraries for three different aminoglycoside antibiotics (amikacin, gentamicin, and tobramycin). At the genome-scale, we show significant (p<0.05) overlap in genes identified for each aminoglycoside evaluated. Among the genomic segments identified, we confirmed increased resistance associated with an increased copy number of several genomic regions, including the ORF of PA5471, recently implicated in MexXY efflux pump related aminoglycoside resistance, PA4943-PA4946 (encoding a probable GTP-binding protein, a predicted host factor I protein, a delta 2-isopentenylpyrophosphate transferase, and DNA mismatch repair protein mutL), PA0960-PA0963 (encoding hypothetical proteins, a probable cold shock protein, a probable DNA-binding stress protein, and aspartyl-tRNA synthetase), a segment of PA4967 (encoding a topoisomerase IV subunit B), as well as a chimeric clone containing two inserts including the ORFs PA0547 and PA2326 (encoding a probable transcriptional regulator and a probable hypothetical protein, respectively). CONCLUSIONS:The studies reported here demonstrate the application of new a genomic method, SCALEs, which can be used to improve understanding of the evolution of antibiotic resistance in P. aeruginosa. In our demonstration studies, we identified a significant number of genomic regions that increased resistance to multiple aminoglycosides. We identified genetic regions that include open reading frames that encode for products from many functional categories, including genes related to O-antigen synthesis, DNA repair, and transcriptional and translational processes