Identification of male-specific volatiles from Neartic and Neotropical stink bugs (Heteroptera: Pentatomidae).

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Visualizing Kinetically Robust (Co4L6)-L-III Assemblies in Vivo: SPECT Imaging of the Encapsulated [Tc-99m]TcO4- Anion

© 2018 American Chemical Society. Noncovalent encapsulation is an attractive approach for modifying the efficacy and physiochemical properties of both therapeutic and diagnostic species. Abiotic self-assembled constructs have shown promise, yet many hurdles between in vitro and (pre)clinical studies remain, not least the challenges associated with maintaining the macromolecular, hollow structure under nonequilibrium conditions. Using a kinetically robust CoIII4L6 tetrahedron we now show the feasibility of encapsulating the most widely used precursor in clinical nuclear diagnostic imaging, the I-emitting [99mTc]TcO4- anion, under conditions compatible with in vivo administration. Subsequent single-photon emission computed tomography imaging of the caged-anion reveals a marked change in the biodistribution compared to the thyroid-accumulating free oxo-anion, thus moving clinical applications of (metallo)supramolecular species a step closer

Non-equilibrium cobalt(III) "click" capsules

Cobalt(III) tetrahedral capsules have been prepared using an assembly-followed-by-oxidation protocol from a cobalt(II) precursor and a readily derivatizable pyridyl-triazole ligand system. Experiments designed to probe the constitutional dynamics show that these architectures are in a non-equilibrium state. A preliminary investigation into the host–guest chemistry of a water-soluble derivative shows it can bind and differentiate a range of different neutral organic molecules. The stability of this ensemble also permits the study of guest-binding at high salt concentrations

Effect of topical honey application along with intralesional injection of glucantime in the treatment of cutaneous leishmaniasis

<p>Abstract</p> <p>Background</p> <p>Leishmaniasis is an endemic disease in Iran. Although many treatments have been suggested for this disease, there hasn't been an effective and safe treatment yet. Regarding the healing effect of honey in the chronic ulcers and its reported therapeutic effect in cutaneous leishmaniasis, we performed a study to better evaluate the efficacy of honey in cutaneous leishmaniasis and its final scar.</p> <p>Methods</p> <p>In a prospective clinical trial, 100 patients with confirmed cutaneous leishmaniasis were selected and randomized into 2 groups. Group A were treated with topical honey twice daily along with intralesional injection of glucantime once weekly until complete healing of the ulcer or for maximum of 6 weeks. Group B were treated with intralesional injection of glucantime alone until complete healing of the ulcer or for a maximum of 6 weeks, too. The patients were followed for 4 months. The collected data were analyzed statistically using statistical tests including Chi-square, Mann Whitney and Kaplan – Mayer tests.</p> <p>Results</p> <p>In this study, 45 patients that had cutaneous leishmaniasis were treated with intralesional glucantime alone and 45 patients were treated with topical honey and glucantime . Ten patients left out the study. In the glucantime alone treated group, 32 patients (71.1%) had complete cure whereas in the group treated with both glucantime & topical honey, 23 patients (51.1%) achieved complete cure. This difference was significant statistically (p = 0.04).</p> <p>Conclusion</p> <p>Further studies to better clarify the efficacy of honey in cutaneous leishmaniasis is needed. We suggest that in another study, the efficacy of honey with standardized level of antibacterial activity is evaluated against cutaneous leishmaniasis.</p

A truncated [Mn^III ₁₂] tetrahedron from oxime-based [Mn^III ₃O] building blocks

The use of the novel pro-ligand H4L combining the complimentary phenolic oxime and diethanolamine moieties in one organic framework, results in the formation of the first example of a [Mn-12(III)] truncated tetrahedron and an extremely rare example of a Mn cage conforming to an Archimedean solid

Susceptibility of optimal train schedules to stochastic disturbances of process times

This work focuses on the stochastic evaluation of train schedules computed by a microscopic scheduler of railway operations based on deterministic information. The research question is to assess the degree of sensitivity of various rescheduling algorithms to variations in process times (running and dwell times). In fact, the objective of railway traffic management is to reduce delay propagation and to increase disturbance robustness of train schedules at a network scale. We present a quantitative study of traffic disturbances and their effects on the schedules computed by simple and advanced rescheduling algorithms. Computational results are based on a complex and densely occupied Dutch railway area; train delays are computed based on accepted statistical distributions, and dwell and running times of trains are subject to additional stochastic variations. From the results obtained on a real case study, an advanced branch and bound algorithm, on average, outperforms a First In First Out scheduling rule both in deterministic and stochastic traffic scenarios. However, the characteristic of the stochastic processes and the way a stochastic instance is handled turn out to have a serious impact on the scheduler performance

Medical-grade honey enriched with antimicrobial peptides has enhanced activity against antibiotic-resistant pathogens

Honey has potent activity against both antibiotic-sensitive and -resistant bacteria, and is an interesting agent for topical antimicrobial application to wounds. As honey is diluted by wound exudate, rapid bactericidal activity up to high dilution is a prerequisite for its successful application. We investigated the kinetics of the killing of antibiotic-resistant bacteria by RS honey, the source for the production of Revamil® medical-grade honey, and we aimed to enhance the rapid bactericidal activity of RS honey by enrichment with its endogenous compounds or the addition of antimicrobial peptides (AMPs). RS honey killed antibiotic-resistant isolates of Pseudomonas aeruginosa, Staphylococcus epidermidis, Enterococcus faecium, and Burkholderia cepacia within 2 h, but lacked such rapid activity against methicillin-resistant S. aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. It was not feasible to enhance the rapid activity of RS honey by enrichment with endogenous compounds, but RS honey enriched with 75 μM of the synthetic peptide Bactericidal Peptide 2 (BP2) showed rapid bactericidal activity against all species tested, including MRSA and ESBL E. coli, at up to 10–20-fold dilution. RS honey enriched with BP2 rapidly killed all bacteria tested and had a broader spectrum of bactericidal activity than either BP2 or honey alone

The Interdomain Linker of AAV-2 Rep68 Is an Integral Part of Its Oligomerization Domain: Role of a Conserved SF3 Helicase Residue in Oligomerization

The four Rep proteins of adeno-associated virus (AAV) orchestrate all aspects of its viral life cycle, including transcription regulation, DNA replication, virus assembly, and site-specific integration of the viral genome into the human chromosome 19. All Rep proteins share a central SF3 superfamily helicase domain. In other SF3 members this domain is sufficient to induce oligomerization. However, the helicase domain in AAV Rep proteins (i.e. Rep40/Rep52) as shown by its monomeric characteristic, is not able to mediate stable oligomerization. This observation led us to hypothesize the existence of an as yet undefined structural determinant that regulates Rep oligomerization. In this document, we described a detailed structural comparison between the helicase domains of AAV-2 Rep proteins and those of the other SF3 members. This analysis shows a major structural difference residing in the small oligomerization sub-domain (OD) of Rep helicase domain. In addition, secondary structure prediction of the linker connecting the helicase domain to the origin-binding domain (OBD) indicates the potential to form α-helices. We demonstrate that mutant Rep40 constructs containing different lengths of the linker are able to form dimers, and in the presence of ATP/ADP, larger oligomers. We further identified an aromatic linker residue (Y224) that is critical for oligomerization, establishing it as a conserved signature motif in SF3 helicases. Mutation of this residue critically affects oligomerization as well as completely abolishes the ability to produce infectious virus. Taken together, our data support a model where the linker residues preceding the helicase domain fold into an α-helix that becomes an integral part of the helicase domain and is critical for the oligomerization and function of Rep68/78 proteins through cooperative interaction with the OBD and helicase domains

Biosentinel: Developing a Space Radiation Biosensor

Ionizing radiation presents a major challenge to human exploration and long-term residence in space. The deep-space radiation spectrum includes highly energetic particles that generate double strand breaks (DSBs), deleterious DNA lesions that are usually repaired without errors via homologous recombination (HR), a conserved pathway in all eukaryotes. While progress identifying and characterizing biological radiation effects using Earth-based facilities has been significant, no terrestrial source duplicates the unique space radiation environment.We are developing a biosensor-based nanosatellite to fly aboard NASAs Space Launch System Exploration Mission 1, expected to launch in 2017 and reach a 1AU (astronomic unit) heliocentric orbit. Our biosensor (called BioSentinel) uses the yeast S. cerevisiae to measure DSBs in response to ambient space radiation. The BioSentinel strain contains engineered genetic defects that prevent growth until and unless a radiation-induced DSB near a reporter gene activates the yeasts HR repair mechanisms. Thus, culture growth and metabolic activity directly indicate a successful DSB-and-repair event. In parallel, HR-defective and wild type strains will provide survival data. Desiccated cells will be carried within independent culture microwells, built into 96-well microfluidic cards. Each microwell set will be activated by media addition at different time points over 18 months, and cell growth will be tracked continuously via optical density. One reserve set will be activated only in the occurrence of a solar particle event. Biological measurements will be compared to data provided by onboard physical dosimeters and to Earth-based experiments.BioSentinel will conduct the first study of biological response to space radiation outside Low Earth Orbit in over 40 years. BioSentinel will thus address strategic knowledge gaps related to the biological effects of space radiation and will provide an adaptable platform to perform human-relevant measurements in multiple space environments. We hope that it can therefore be used on the ISS, on and around other planetary bodies as well as other exploration platforms as a self-contained system that will allow us to compare and calibrate different radiation environments.BioSentinels results will be critical for improving interpretation of the effects of space radiation exposure, and for reducing the risk associated with long-term human exploration