A Small Family of Elements with Long Inverted Repeats is Located Near Sites of Developmentally Regulated DNA Rearrangement in \u3cem\u3eTetrahymena thermophila\u3c/em\u3e

Extensive DNA rearrangement occurs during the development of the somatic macronucleus from the germ line micronucleus in ciliated protozoans. The micronuclear junctions and the macronuclear product of a developmentally regulated DNA rearrangement in Tetrahymena thermophila, Tlr1, have been cloned. The intrachromosomal rearrangement joins sequences that are separated by more than 13 kb in the micronucleus with the elimination of moderately repeated micronucleus-specific DNA sequences. There is a long, 825-bp, inverted repeat near the micronuclear junctions. The inverted repeat contains two different 19-bp tandem repeats. The 19-bp repeats are associated with each other and with DNA rearrangements at seven locations in the micronuclear genome. Southern blot analysis is consistent with the occurrence of the 19-bp repeats within pairs of larger repeated sequences. Another family member was isolated. The 19-mers in that clone are also in close proximity to a rearrangement junction. We propose that the 19-mers define a small family of developmentally regulated DNA rearrangements having elements with long inverted repeats near the junction sites. We discuss the possibility that transposable elements evolve by capture of molecular machinery required for essential cellular functions

Mutations in PNKD causing paroxysmal dyskinesia alters protein cleavage and stability.

Paroxysmal non-kinesigenic dyskinesia (PNKD) is a rare autosomal dominant movement disorder triggered by stress, fatigue or consumption of either alcohol or caffeine. Attacks last 1-4 h and consist of dramatic dystonia and choreoathetosis in the limbs, trunk and face. The disease is associated with single amino acid changes (A7V or A9V) in PNKD, a protein of unknown function. Here we studied the stability, cellular localization and enzymatic activity of the PNKD protein in cultured cells and transgenic animals. The N-terminus of the wild-type (WT) long PNKD isoform (PNKD-L) undergoes a cleavage event in vitro, resistance to which is conferred by disease-associated mutations. Mutant PNKD-L protein is degraded faster than the WT protein. These results suggest that the disease mutations underlying PNKD may disrupt protein processing in vivo, a hypothesis supported by our observation of decreased cortical Pnkd-L levels in mutant transgenic mice. Pnkd is homologous to a superfamily of enzymes with conserved β-lactamase domains. It shares highest homology with glyoxalase II but does not catalyze the same reaction. Lower glutathione levels were found in cortex lysates from Pnkd knockout mice versus WT littermates. Taken together, our results suggest an important role for the Pnkd protein in maintaining cellular redox status

Spatially resolved MaNGA observations of the host galaxy of superluminous supernova 2017egm

Superluminous supernovae (SLSNe) are found predominantly in dwarf galaxies, indicating that their progenitors have a low metallicity. However, the most nearby SLSN to date, SN 2017egm, occurred in the spiral galaxy NGC 3191, which has a relatively high stellar mass and correspondingly high metallicity. In this paper, we present detailed analysis of the nearby environment of SN 2017egm using MaNGA IFU data, which provides spectral data on kiloparsec scales. From the velocity map we find no evidence that SN 2017egm occurred within some intervening satellite galaxy, and at the SN position most metallicity diagnostics yield a solar and above solar metallicity (12 + log (O/H) = 8.8-9.1). Additionally we measure a small H-alpha equivalent width (EW) at the SN position of just 34 Angs, which is one of the lowest EWs measured at any SLSN or Gamma-Ray Burst position, and indicative of the progenitor star being comparatively old. We also compare the observed properties of NGC 3191 with other SLSN host galaxies. The solar-metallicity environment at the position of SN 2017egm presents a challenge to our theoretical understanding, and our spatially resolved spectral analysis provides further constraints on the progenitors of SLSNe.Comment: Accepted version in ApJ Letter. Thank you for useful comment

Characterization of a continuous feline mammary epithelial cell line susceptible to feline epitheliotropic viruses.

Mucosal epithelial cells are the primary targets for many common viral pathogens of cats. Viral infection of epithelia can damage or disrupt the epithelial barrier that protects underlying tissues. In vitro cell culture systems are an effective means to study how viruses infect and disrupt epithelial barriers, however no true continuous or immortalized feline epithelial cell culture lines are available. A continuous cell culture of feline mammary epithelial cells (FMEC UCD-04-2) that forms tight junctions with high transepithelial electrical resistance (>2000Omegacm(-1)) 3-4 days after reaching confluence was characterized. In addition, it was shown that FMECs are susceptible to infection with feline calicivirus (FCV), feline herpesvirus (FHV-1), feline coronavirus (FeCoV), and feline panleukopenia virus (FPV). These cells will be useful for studies of feline viral disease and for in vitro studies of feline epithelia

Tailoring the surface charge of dextran-based polymer coated SPIONs for modulated stem cell uptake and MRI contrast

Tracking stem cells in vivo using non-invasive techniques is critical to evaluate the efficacy and safety of stem cell therapies. Superparamagnetic iron oxide nanoparticles (SPIONs) enable cells to be tracked using magnetic resonance imaging (MRI), but to obtain detectable signal cells need to be labelled with a sufficient amount of iron oxide. For the majority of SPIONs, this can only be obtained with the use of transfection agents, which can adversely affect cell health. Here, we have synthesised a library of dextran-based polymer coated SPIONs with varying surface charge from −1.5 mV to +18.2 mV via a co-precipitation approach and investigated their ability to be directly internalised by stem cells without the need for transfection agents. The SPIONs were colloidally stable in physiological solutions. The crystalline phase of the particles was confirmed with powder X-ray diffraction and their magnetic properties were characterised using SQUID magnetometry and magnetic resonance. Increased surface charge led to six-fold increase in uptake of particles into stem cells and higher MRI contrast, with negligible change in cell viability. Cell tracking velocimetry was shown to be a more accurate method for predicting MRI contrast of stem cells compared to measuring iron oxide uptake through conventional bulk iron quantification

Mentorship in the Field of Aging: Purposes, Pivots, and Priorities

The Gerontological Society of America (GSA) is a multi-disciplinary organization dedicated to advancing the field of aging and improving the lives of older adults. With a long-standing commitment to mentorship and career development, this article focuses on GSA’s Mentoring Consultancies and Career Conversations events and their pivot to meet the needs and demands of current and future gerontologists amid the COVID-19 pandemic. This article provides a description of these events in the context of planning, content, and member engagement. Recommendations are provided to other organizations seeking to enrich their membership through mentorship and career development activities

Using a model of group psychotherapy to support social research on sensitive topics

This article describes the exploratory use of professional therapeutic support by social researchers working on a sensitive topic. Talking to recently bereaved parents about the financial implications of their child's death was expected to be demanding work, and the research design included access to an independent psychotherapeutic service. Using this kind of professional support is rare within the general social research community, and it is useful to reflect on the process. There are likely to be implications for collection and interpretation of data, research output and the role and experience of the therapist. Here, the primary focus is the potential impact on researcher well-being