Single-crystal X-ray diffraction and NMR crystallography of a 1:1 cocrystal of dithianon and pyrimethanil

A single-crystal X-ray diffraction structure of a 1:1 cocrystal of two fungicides, namely di­thia­non (DI) and pyrimethanil (PM), is reported [systematic name: 5,10-dioxo-5H,10H-naphtho­[2,3-b][1,4]dithiine-2,3-dicarbo­nitrile–4,6-dimethyl-N-phenyl­pyrimidin-2-amine (1/1), C14H4N2O2S2·C12H13N2]. Following an NMR crystallography approach, experimental solid-state magic angle spinning (MAS) NMR spectra are presented together with GIPAW (gauge-including projector augmented wave) calculations of NMR chemical shieldings. Specifically, experimental 1H and 13C chemical shifts are determined from two-dimensional 1H–13C MAS NMR correlation spectra recorded with short and longer contact times so as to probe one-bond C—H connectivities and longer-range C...H proximities, whereas H...H proximities are identified in a 1H double-quantum (DQ) MAS NMR spectrum. The performing of separate GIPAW calculations for the full periodic crystal structure and for isolated mol­ecules allows the determination of the change in chemical shift upon going from an isolated mol­ecule to the full crystal structure. For the 1H NMR chemical shifts, changes of 3.6 and 2.0 ppm correspond to inter­molecular N—H...O and C—H...O hydrogen bonding, while changes of −2.7 and −1.5 ppm are due to ring current effects associated with C—H...π inter­actions. Even though there is a close inter­molecular S...O distance of 3.10 Å, it is of note that the mol­ecule-to-crystal chemical shifts for the involved sulfur or oxygen nuclei are small

Establishment of a positive-readout reporter system for siRNAs

The use of small interfering RNA molecules for therapeutic applications requires development of improved delivery systems, a process that would be facilitated by a non-invasive positive-readout mouse model for studying siRNA pharmacodynamics. Positive readout would yield better signal/noise ratios than existing negative-readout systems. We have engineered a positive-readout luciferase reporter system, activated by successful delivery of siRNA targeting the lac repressor. Co-transfection of a plasmid expressing lac repressor and a plasmid expressing firefly luciferase under the control of an RSV promoter, containing two lac operator sites, resulted in 5.7-fold lower luciferase activity than luciferase-encoding plasmid alone. Inhibition was reversed following addition of synthetic inducer, IPTG, which elevated luciferase expression to normal levels and confirmed functionality of the lac operon. Delivery of 1nM siRNA targeting lac repressor to repressor/reporter co-transfected cells was sufficient to fully restore luciferase expression to levels observed in the absence of repressor. Maximum expression was observed after 48hr, with a rapid decrease thereafter due to the short half life of luciferase. The luciferase positive-readout reporter system is therefore a dynamic indicator of successful RNAi delivery in vitro and could be adapted to generate a transgenic mouse capable of reporting RNAi activity non-invasively in vivo

Mental health among healthcare workers and other vulnerable groups during the COVID-19 pandemic and other coronavirus outbreaks: A rapid systematic review.

INTRODUCTION: Although most countries and healthcare systems worldwide have been affected by the COVID-19 pandemic, some groups of the population may be more vulnerable to detrimental effects of the pandemic on mental health than others. The aim of this systematic review was to synthesise evidence currently available from systematic reviews on the impact of COVID-19 and other coronavirus outbreaks on mental health for groups of the population thought to be at increased risk of detrimental mental health impacts. MATERIALS AND METHODS: We conducted a systematic review of reviews on adults and children residing in a country affected by a coronavirus outbreak and belonging to a group considered to be at risk of experiencing mental health inequalities. Data were collected on symptoms or diagnoses of any mental health condition, quality of life, suicide or attempted suicide. The protocol for this systematic review was registered in the online PROSPERO database prior to commencing the review (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=194264). RESULTS: We included 25 systematic reviews. Most reviews included primary studies of hospital workers from multiple countries. Reviews reported variable estimates for the burden of symptoms of mental health problems among acute healthcare workers, COVID-19 patients with physical comorbidities, and children and adolescents. No evaluations of interventions were identified. Risk- and protective factors, mostly for healthcare workers, showed the importance of personal factors, the work environment, and social networks for mental health. CONCLUSIONS: This review of reviews based on primary studies conducted in the early months of the COVID-19 pandemic shows a lack of evidence on mental health interventions and mental health impacts on vulnerable groups in the population

The Spitzer High Redshift Radio Galaxy Survey

We present results from a comprehensive imaging survey of 70 radio galaxies at redshifts 1<z<5.2 using all three cameras onboard the Spitzer Space Telescope. The resulting spectral energy distributions unambiguously show a stellar population in 46 sources and hot dust emission associated with the active nucleus in 59. Using a new restframe S_3um/S_1.6um versus S_um/S_3um criterion, we identify 42 sources where the restframe 1.6um emission from the stellar population can be measured. For these radio galaxies, the median stellar mass is high, 2x10^11 M_sun, and remarkably constant within the range 13, there is tentative evidence for a factor of two decrease in stellar mass. This suggests that radio galaxies have assembled the bulk of their stellar mass by z~3, but confirmation by more detailed decomposition of stellar and AGN emission is needed. The restframe 500 MHz radio luminosities are only marginally correlated with stellar mass but are strongly correlated with the restframe 5um hot dust luminosity. This suggests that the radio galaxies have a large range of Eddington ratios. We also present new Very Large Array 4.86 and 8.46 GHz imaging of 14 radio galaxies and find that radio core dominance --- an indicator of jet orientation --- is strongly correlated with hot dust luminosity. While all of our targets were selected as narrow-lined, type 2 AGNs, this result can be understood in the context of orientation-dependent models if there is a continuous distribution of orientations from obscured type 2 to unobscured type 1 AGNs rather than a clear dichotomy. Finally, four radio galaxies have nearby (<6") companions whose mid-IR colors are suggestive of their being AGNs. This may indicate an association between radio galaxy activity and major mergers.Comment: 31 pages, 125 figures. Accepted for publication in the Astrophysical Journa

Characterization of cleavage events in the multifunctional cilium adhesin Mhp684 (P146) reveals a mechanism by which mycoplasma hyopneumoniae regulates surface topography

Mycoplasma hyopneumoniae causes enormous economic losses to swine production worldwide by colonizing the ciliated epithelium in the porcine respiratory tract, resulting in widespread damage to the mucociliary escalator, prolonged inflammation, reduced weight gain, and secondary infections. Protein Mhp684 (P146) comprises 1,317 amino acids, and while the N-terminal 400 residues display significant sequence identity to the archetype cilium adhesin P97, the remainder of the molecule is novel and displays unusual motifs. Proteome analysis shows that P146 preprotein is endogenously cleaved into three major fragments identified here as P50P146, P40P146, and P85P146 that reside on the cell surface. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) identified a semitryptic peptide that delineated a major cleavage site in Mhp684. Cleavage occurred at the phenylalanine residue within sequence 672ATEF2QQ677, consistent with a cleavage motif resembling S/T-X-F2XD/E recently identified in Mhp683 and other P97/P102 family members. Biotinylated surface proteins recovered by avidin chromatography and separated by two-dimensional gel electrophoresis (2-D GE) showed that more-extensive endoproteolytic cleavage of P146 occurs. Recombinant fragments F1P146-F3P146 that mimic P50P146, P40P146, and P85P146 were constructed and shown to bind porcine epithelial cilia and biotinylated heparin with physiologically relevant affinity. Recombinant versions of F3P146 generated from M. hyopneumoniae strain J and 232 sequences strongly bind porcine plasminogen, and the removal of their respective C-terminal lysine and arginine residues significantly reduces this interaction. These data reveal that P146 is an extensively processed, multifunctional adhesin of M. hyopneumoniae. Extensive cleavage coupled with variable cleavage efficiency provides a mechanism by which M. hyopneumoniae regulates protein topography

Enhanced Nonperturbative Effects in Z Decays to Hadrons

We use soft collinear effective field theory (SCET) to study nonperturbative strong interaction effects in Z decays to hadronic final states that are enhanced in corners of phase space. These occur, for example, in the jet energy distribution for two jet events near E_J=M_Z/2, the thrust distribution near unity and the jet invariant mass distribution near zero. The extent to which such nonperturbative effects for different observables are related is discussed.Comment: 17 pages. Paper reorganized, and more discussion and results include

Comparison of TaqMan PCR assays for detection of the melioidosis agent Burkholderia pseudomallei in clinical specimens

Melioidosis is an emerging infectious disease caused by the soil bacterium Burkholderia pseudomallei. In diagnostic and forensic settings, molecular detection assays need not only high sensitivity with low limits of detection but also high specificity. In a direct comparison of published and newly developed TaqMan PCR assays, we found the TTS1-orf2 assay to be superior in detecting B. pseudomallei directly from clinical specimens. The YLF/BTFC multiplex assay (targeting the Yersinia-like fimbrial/Burkholderia thailandensis-like flagellum and chemotaxis region) also showed high diagnostic sensitivity and provides additional information on possible geographic origin

Comparison of TaqMan PCR assays for detection of the melioidosis agent Burkholderia pseudomallei in clinical specimens

Melioidosis is an emerging infectious disease caused by the soil bacterium Burkholderia pseudomallei. In diagnostic and forensic settings, molecular detection assays need not only high sensitivity with low limits of detection but also high specificity. In a direct comparison of published and newly developed TaqMan PCR assays, we found the TTS1-orf2 assay to be superior in detecting B. pseudomallei directly from clinical specimens. The YLF/BTFC multiplex assay (targeting the Yersinia-like fimbrial/Burkholderia thailandensis-like flagellum and chemotaxis region) also showed high diagnostic sensitivity and provides additional information on possible geographic origin