Maintenance of complex I and its supercomplexes by NDUF-11 is essential for mitochondrial structure, function and health

Mitochondrial supercomplexes form around a conserved core of monomeric complex I and dimeric complex III; wherein a subunit of the former, NDUFA11, is conspicuously situated at the interface. We identified nduf-11 (B0491.5) as encoding the Caenorhabditis elegans homologue of NDUFA11. Animals homozygous for a CRISPR-Cas9-generated knockout allele of nduf-11 arrested at the second larval (L2) development stage. Reducing (but not eliminating) expression using RNAi allowed development to adulthood, enabling characterisation of the consequences: destabilisation of complex I and its supercomplexes and perturbation of respiratory function. The loss of NADH dehydrogenase activity was compensated by enhanced complex II activity, with the potential for detrimental reactive oxygen species (ROS) production. Cryo-electron tomography highlighted aberrant morphology of cristae and widening of both cristae junctions and the intermembrane space. The requirement of NDUF-11 for balanced respiration, mitochondrial morphology and development presumably arises due to its involvement in complex I and supercomplex maintenance. This highlights the importance of respiratory complex integrity for health and the potential for its perturbation to cause mitochondrial disease. This article has an associated First Person interview with Amber Knapp-Wilson, joint first author of the paper

Persistent starspot signals on M dwarfs: multi-wavelength Doppler observations with the Habitable-zone Planet Finder and Keck/HIRES

Young, rapidly-rotating M dwarfs exhibit prominent starspots, which create quasiperiodic signals in their photometric and Doppler spectroscopic measurements. The periodic Doppler signals can mimic radial velocity (RV) changes expected from orbiting exoplanets. Exoplanets can be distinguished from activity-induced false positives by the chromaticity and long-term incoherence of starspot signals, but these qualities are poorly constrained for fully-convective M stars. Coherent photometric starspot signals on M dwarfs may persist for hundreds of rotations, and the wavelength dependence of starspot RV signals may not be consistent between stars due to differences in their magnetic fields and active regions. We obtained precise multi-wavelength RVs of four rapidly-rotating M dwarfs (AD Leo, G 227-22, GJ 1245B, GJ 3959) using the near-infrared (NIR) Habitable-zone Planet Finder, and the optical Keck/HIRES spectrometer. Our RVs are complemented by photometry from Kepler, TESS, and the Las Cumbres Observatory (LCO) network of telescopes. We found that all four stars exhibit large spot-induced Doppler signals at their rotation periods, and investigated the longevity and optical-to-NIR chromaticity for these signals. The phase curves remain coherent much longer than is typical for Sunlike stars. Their chromaticity varies, and one star (GJ 3959) exhibits optical and NIR RV modulation consistent in both phase and amplitude. In general, though, we find that the NIR amplitudes are lower than their optical counterparts. We conclude that starspot modulation for rapidly-rotating M stars frequently remains coherent for hundreds of stellar rotations, and gives rise to Doppler signals that, due to this coherence, may be mistaken for exoplanets.Comment: Accepted for publication in the Astrophysical Journa

Persistent Starspot Signals on M Dwarfs: Multiwavelength Doppler Observations with the Habitable-zone Planet Finder and Keck/HIRES

Young, rapidly rotating M dwarfs exhibit prominent starspots, which create quasiperiodic signals in their photometric and Doppler spectroscopic measurements. The periodic Doppler signals can mimic radial velocity (RV) changes expected from orbiting exoplanets. Exoplanets can be distinguished from activity-induced false positives by the chromaticity and long-term incoherence of starspot signals, but these qualities are poorly constrained for fully convective M stars. Coherent photometric starspot signals on M dwarfs may persist for hundreds of rotations, and the wavelength dependence of starspot RV signals may not be consistent between stars due to differences in their magnetic fields and active regions. We obtained precise multiwavelength RVs of four rapidly rotating M dwarfs (AD Leo, G227-22, GJ 1245B, GJ 3959) using the near-infrared (NIR) Habitable-zone Planet Finder and the optical Keck/HIRES spectrometer. Our RVs are complemented by photometry from Kepler, TESS, and the Las Cumbres Observatory network of telescopes. We found that all four stars exhibit large spot-induced Doppler signals at their rotation periods, and investigated the longevity and optical-to-NIR chromaticity for these signals. The phase curves remain coherent much longer than is typical for Sunlike stars. Their chromaticity varies, and one star (GJ 3959) exhibits optical and NIR RV modulation consistent in both phase and amplitude. In general, though, we find that the NIR amplitudes are lower than their optical counterparts. We conclude that starspot modulation for rapidly rotating M stars frequently remains coherent for hundreds of stellar rotations and gives rise to Doppler signals that, due to this coherence, may be mistaken for exoplanets

A warm Jupiter transiting an M dwarf: A TESS single transit event confirmed with the Habitable-zone Planet Finder

We confirm the planetary nature of a warm Jupiter transiting the early M dwarf TOI-1899, using a combination of available TESS photometry; high-precision, near-infrared spectroscopy with the Habitable-zone Planet Finder; and speckle and adaptive optics imaging. The data reveal a transiting companion on an $\sim29$-day orbit with a mass and radius of $0.66\pm0.07\ \mathrm{M_{J}}$and$1.15_{-0.05}^{+0.04}\ \mathrm{R_{J}}$, respectively. The star TOI-1899 is the lowest-mass star known to host a transiting warm Jupiter, and we discuss the follow-up opportunities afforded by a warm ($\mathrm{T_{eq}}\sim362$ K) gas giant orbiting an M0 star. Our observations reveal that TOI-1899.01 is a puffy warm Jupiter, and we suggest additional transit observations to both refine the orbit and constrain the true dilution observed in TESS.Comment: 24 pages, 5 figures, 3 tables, published in A

Validation of food store environment secondary data source and the role of neighborhood deprivation in Appalachia, Kentucky

Background Based on the need for better measurement of the retail food environment in rural settings and to examine how deprivation may be unique in rural settings, the aims of this study were: 1) to validate one commercially available data source with direct field observations of food retailers; and 2) to examine the association between modified neighborhood deprivation and the modified retail food environment score (mRFEI). Methods Secondary data were obtained from a commercial database, InfoUSA in 2011, on all retail food outlets for each census tract. In 2011, direct observation identifying all listed food retailers was conducted in 14 counties in Kentucky. Sensitivity and positive predictive values (PPV) were compared. Neighborhood deprivation index was derived from American Community Survey data. Multinomial regression was used to examine associations between neighborhood deprivation and the mRFEI score (indicator of retailers selling healthy foods such as low-fat foods and fruits and vegetables relative to retailers selling more energy dense foods). Results The sensitivity of the commercial database was high for traditional food retailers (grocery stores, supermarkets, convenience stores), with a range of 0.96-1.00, but lower for non-traditional food retailers; dollar stores (0.20) and Farmer’s Markets (0.50). For traditional food outlets, the PPV for smaller non-chain grocery stores was 38%, and large chain supermarkets was 87%. Compared to those with no stores in their neighborhoods, those with a supercenter [OR 0.50 (95% CI 0.27. 0.97)] or convenience store [OR 0.67 (95% CI 0.51, 0.89)] in their neighborhood have lower odds of living in a low deprivation neighborhood relative to a high deprivation neighborhood. Conclusion The secondary commercial database used in this study was insufficient to characterize the rural retail food environment. Our findings suggest that neighborhoods with high neighborhood deprivation are associated with having certain store types that may promote less healthy food options

Redundant Mechanisms Prevent Mitotic Entry Following Replication Arrest in the Absence of Cdc25 Hyper-Phosphorylation in Fission Yeast

Following replication arrest the Cdc25 phosphatase is phosphorylated and inhibited by Cds1. It has previously been reported that expressing Cdc25 where 9 putative amino-terminal Cds1 phosphorylation sites have been substituted to alanine results in bypass of the DNA replication checkpoint. However, these results were acquired by expression of the phosphorylation mutant using a multicopy expression vector in a genetic background where the DNA replication checkpoint is intact. In order to clarify these results we constructed a Cdc25(9A)-GFP native promoter integrant and examined its effect on the replication checkpoint at endogenous expression levels. In this strain the replication checkpoint operates normally, conditional on the presence of the Mik1 kinase. In response to replication arrest the Cdc25(9A)-GFP protein is degraded, suggesting the presence of a backup mechanism to eliminate the phosphatase when it cannot be inhibited through phosphorylation

A Baseline for the Multivariate Comparison of Resting-State Networks

As the size of functional and structural MRI datasets expands, it becomes increasingly important to establish a baseline from which diagnostic relevance may be determined, a processing strategy that efficiently prepares data for analysis, and a statistical approach that identifies important effects in a manner that is both robust and reproducible. In this paper, we introduce a multivariate analytic approach that optimizes sensitivity and reduces unnecessary testing. We demonstrate the utility of this mega-analytic approach by identifying the effects of age and gender on the resting-state networks (RSNs) of 603 healthy adolescents and adults (mean age: 23.4 years, range: 12–71 years). Data were collected on the same scanner, preprocessed using an automated analysis pipeline based in SPM, and studied using group independent component analysis. RSNs were identified and evaluated in terms of three primary outcome measures: time course spectral power, spatial map intensity, and functional network connectivity. Results revealed robust effects of age on all three outcome measures, largely indicating decreases in network coherence and connectivity with increasing age. Gender effects were of smaller magnitude but suggested stronger intra-network connectivity in females and more inter-network connectivity in males, particularly with regard to sensorimotor networks. These findings, along with the analysis approach and statistical framework described here, provide a useful baseline for future investigations of brain networks in health and disease