Ytterbium triflate (and trimethylsilyl triflate) catalyzed isomerization of glycidic esters to α-hydroxy-β,γ-unsaturated esters and their conversion into cyclopentanoids using Johnson-Claisen rearrangement

A variety of glycidic esters undergo smooth isomerization to the corresponding α-hydroxy-β, γ-unsaturated esters upon reaction with Yb(OTf)3 or TMSOTf. These α-hydroxy-β, γ-unsaturated esters undergo Johnson-Claisen rearrangement to appropriately substituted diesters, some of which are converted into cyclopentanoids

Therapeutic efficacy of favipiravir against Bourbon virus in mice

Bourbon virus (BRBV) is an emerging tick-borne RNA virus in the orthomyxoviridae family that was discovered in 2014. Although fatal human cases of BRBV have been described, little is known about its pathogenesis, and no antiviral therapies or vaccines exist. We obtained serum from a fatal case in 2017 and successfully recovered the second human infectious isolate of BRBV. Next-generation sequencing of the St. Louis isolate of BRBV (BRBV-STL) showed >99% nucleotide identity to the original reference isolate. Using BRBV-STL, we developed a small animal model to study BRBV-STL tropism in vivo and evaluated the prophylactic and therapeutic efficacy of the experimental antiviral drug favipiravir against BRBV-induced disease. Infection of Ifnar1-/- mice lacking the type I interferon receptor, but not congenic wild-type animals, resulted in uniformly fatal disease 6 to 10 days after infection. RNA in situ hybridization and viral yield assays demonstrated a broad tropism of BRBV-STL with highest levels detected in liver and spleen. In vitro replication and polymerase activity of BRBV-STL were inhibited by favipiravir. Moreover, administration of favipiravir as a prophylaxis or as post-exposure therapy three days after infection prevented BRBV-STL-induced mortality in immunocompromised Ifnar1-/- mice. These results suggest that favipiravir may be a candidate treatment for humans who become infected with BRBV

MMP-2 mediates local degradation and remodeling of collagen by annulus fibrosus cells of the intervertebral disc

Degeneration of the intervertebral disc (IVD) is characterized by marked degradation and restructuring of the annulus fibrosus (AF). Although several matrix metalloproteinases (MMPs) have been found to be more prevalent in degenerate discs, their coordination and function within the context of the disease process are still not well understood. In this study, we sought to determine whether MMP-2 is associated with degenerative changes in the AF and to identify the manner by which AF cells use MMP-2. Two established animal models of disc degeneration, static compression and transannular needle puncture of rodent caudal discs, were examined for MMP-2 immunopositivity. With lentiviral transduction of an shRNA expression cassette, we screened and identified an effective shRNA sequence for generating stable RNA interference to silence MMP-2 expression in primary rat AF cells. Gelatin films were used to compare gelatinase activity and spatial patterns of degradation between transduced cells, and both noninfected and nonsense shRNA controls. The functional significance of MMP-2 was determined by assessing the ability for cells to remodel collagen gels. Both static compression and 18-g annular puncture of rodent caudal discs stimulated an increase in MMP-2 activity with concurrent lamellar disorganization in the AF, whereas 22-g and 26-g needle injuries did not. To investigate the functional role of MMP-2, we established lentivirus-mediated RNAi to induce stable knockdown of transcript levels by as much as 88%, and protein levels by as much as 95% over a 10-day period. Culturing transduced cells on gelatin films confirmed that MMP-2 is the primary functional gelatinase in AF cells, and that MMP-2 is used locally in regions immediately around AF cells. In collagen gels, transduced cells demonstrated an inability to remodel collagen matrices. Our study indicates that increases in MMP-2 observed in human degenerate discs are mirrored in experimentally induced degenerative changes in rodent animal models. AF cells appear to use MMP-2 in a very directed fashion for local matrix degradation and collagen remodeling. This suggests that MMP-2 may have a functionally significant role in the etiology of degenerative disc disease and could be a potential therapeutic target.https://doi.org/10.1186/ar4224https://doi.org/10.1186/1471-2164-14-28

Mentoring faculty online: a literature review and recommendations for web-based programs

Teaching-focused faculty mentorship programs can expose instructors to new ideas, as well as opportunities for critical self-reflection, professional growth, and network building. In this literature review, we synthesize the research on teaching-focused faculty mentorship programs that have been facilitated at institutions of higher education through online or blended modalities. We identify key trends in the reported outcomes of these programs, as well as aspects of program design and implementation that might enable or impede program success. Finally, we provide eight recommendations to help guide the implementation of online and blended faculty mentorship programs

Evaluation of Nutritional, Phytochemical, and Mineral Composition of Selected Medicinal Plants for Therapeutic Uses from Cold Desert of Western Himalaya

The aim of this study was to determine the elemental and nutritive values of leaf parts of 10 selected wild medicinal plants, Acer pictum, Acer caecium, Betula utilis, Oxalis corniculata, Euphorbia pilosa, Heracleum lanatum, Urtica dioica, Berberis lycium, Berberis asiaticaand, and Quercus ilex, collected from the high hills of the Chitkul range in district Kinnaur, Western Himalaya. The nutritional characteristics of medicinal plant species were analyzed by using muffle furnace and micro-Kjeldahl methods, and the mineral content in plants was analyzed through atomic absorption spectrometry. The highest percentage of used value was reported in Betula utilis (0.42) and the lowest in Quercus ilex (0.17). In this study, it was found that new generations are not much interested in traditional knowledge of ethnomedicinal plants due to modernization in society. Therefore, there is an urgent need to document ethnomedicinal plants along with their phytochemical and minerals analysis in study sites. It was found that rural people in western Himalaya are dependent on wild medicinal plants, and certain steps must be taken to conserve these plants from extinction in the cold desert of Himalayan region. They are an alternative source of medicine because they contain saponin, alkaloid, and flavonoid etc. as well as minerals. The leaves used for analysis possesses good mineral content, such as Na, N, K, P, Zn, Fe, Cu, Mn, Ca, Mg, and S. Hence, in the current study it was observed that medicinal plants are not only used for therapeutic purposes, but they can also be used as nutritional supplements

The MAGPI Survey: Effects of Spiral Arms on Different Tracers of the Interstellar Medium and Stellar Populations at z~0.3

Spiral structures are important drivers of the secular evolution of disc galaxies, however, the origin of spiral arms and their effects on the development of galaxies remain mysterious. In this work, we present two three-armed spiral galaxies at z~0.3 in the Middle Age Galaxy Properties with Integral Field Spectroscopy (MAGPI) survey. Taking advantage of the high spatial resolution (~0.6'') of the Multi-Unit Spectroscopic Unit (MUSE), we investigate the two-dimensional distributions of different spectral parameters: Halpha, gas-phase metallicity, and D4000. We notice significant offsets in Halpha (~0.2 dex) as well as gas-phase metallicities (~0.05 dex) among the spiral arms, downstream and upstream of MAGPI1202197197 (SG1202). This observational signature suggests the spiral structure in SG1202 is consistent with arising from density wave theory. No azimuthal variation in Halpha or gas-phase metallicities is observed in MAGPI1204198199 (SG1204), which can be attributed to the tighter spiral arms in SG1204 than SG1202, coming with stronger mixing effects in the disc. The absence of azimuthal D4000 variation in both galaxies suggests the stars at different ages are well-mixed between the spiral arms and distributed around the disc regions. The different azimuthal distributions in Halpha and D4000 highlight the importance of time scales traced by various spectral parameters when studying 2D distributions in spiral galaxies. This work demonstrates the feasibility of constraining spiral structures by tracing interstellar medium (ISM) and stellar population at z~0.3, with a plan to expand the study to the full MAGPI survey.Comment: 15 pages, 11 figures, 2 tables, accepted for publication in MNRA