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ABSTRACT Age‐related skeletal muscle atrophy, known as sarcopenia, is characterized by loss of muscle mass, strength, endurance, and oxidative capacity. Although exercise has been shown to mitigate sarcopenia, the underlying governing mechanisms are poorly understood. Mitochondrial dysfunction is implicated in aging and sarcopenia; however, few studies explore how mitochondrial structure contributes to this dysfunction. In this study, we sought to understand how aging impacts mitochondrial three‐dimensional (3D) structure and its regulators in skeletal muscle. We hypothesized that aging leads to remodeling of mitochondrial 3D architecture permissive to dysfunction and is ameliorated by exercise. Using serial block‐face scanning electron microscopy (SBF‐SEM) and Amira software, mitochondrial 3D reconstructions from patient biopsies were generated and analyzed. Across five human cohorts, we correlate differences in magnetic resonance imaging, mitochondria 3D structure, exercise parameters, and plasma immune markers between young (under 50 years) and old (over 50 years) individuals. We found that mitochondria are less spherical and more complex, indicating age‐related declines in contact site capacity. Additionally, aged samples showed a larger volume phenotype in both female and male humans, indicating potential mitochondrial swelling. Concomitantly, muscle area, exercise capacity, and mitochondrial dynamic proteins showed age‐related losses. Exercise stimulation restored mitofusin 2 (MFN2), one such of these mitochondrial dynamic proteins, which we show is required for the integrity of mitochondrial structure. Furthermore, we show that this pathway is evolutionarily conserved, as Marf, the MFN2 ortholog inDrosophila, knockdown alters mitochondrial morphology and leads to the downregulation of genes regulating mitochondrial processes. Our results define age‐related structural changes in mitochondria and further suggest that exercise may mitigate age‐related structural decline through modulation of mitofusin 2. 

ABSTRACT Retrieval methods are a powerful analysis technique for modelling exoplanetary atmospheres by estimating the bulk physical and chemical properties that combine in a forward model to best fit an observed spectrum, and they are increasingly being applied to observations of directly imaged exoplanets. We have adapted taurex3, the Bayesian retrieval suite, for the analysis of near-infrared spectrophotometry from directly imaged gas giant exoplanets and brown dwarfs. We demonstrate taurex3’s applicability to sub-stellar atmospheres by presenting results for brown dwarf benchmark GJ 570D which are consistent with previous retrieval studies, whilst also exhibiting systematic biases associated with the presence of alkali lines. We also present results for the cool exoplanet 51 Eri b, the first application of a free chemistry retrieval analysis to this object, using spectroscopic observations from GPI and SPHERE. While our retrieval analysis is able to explain spectroscopic and photometric observations without employing cloud extinction, we conclude this may be a result of employing a flexible temperature-pressure profile which is able to mimic the presence of clouds. We present Bayesian evidence for an ammonia detection with a 2.7σ confidence, the first indication of ammonia in a directly imaged exoplanetary atmosphere. This is consistent with this molecule being present in brown dwarfs of a similar spectral type. We demonstrate the chemical similarities between 51 Eri b and GJ 570D in relation to their retrieved molecular abundances. Finally, we show that overall retrieval conclusions for 51 Eri b can vary when employing different spectral data and modelling components, such as temperature–pressure and cloud structures. 

ABSTRACT The kidney filters nutrient waste and bodily fluids from the bloodstream, in addition to secondary functions of metabolism and hormone secretion, requiring an astonishing amount of energy to maintain its functions. In kidney cells, mitochondria produce adenosine triphosphate (ATP) and help maintain kidney function. Due to aging, the efficiency of kidney functions begins to decrease. Dysfunction in mitochondria and cristae, the inner folds of mitochondria, is a hallmark of aging. Therefore, age-related kidney function decline could be due to changes in mitochondrial ultrastructure, increased reactive oxygen species (ROS), and subsequent alterations in metabolism and lipid composition. We sought to understand if there is altered mitochondrial ultrastructure, as marked by 3D morphological changes, across time in tubular kidney cells. Serial block facing-scanning electron microscope (SBF-SEM) and manual segmentation using the Amira software were used to visualize murine kidney samples during the aging process at 3 months (young) and 2 years (old). We found that 2-year mitochondria are more fragmented, compared to the 3-month, with many uniquely shaped mitochondria observed across aging, concomitant with shifts in ROS, metabolomics, and lipid homeostasis. Furthermore, we show that the mitochondrial contact site and cristae organizing system (MICOS) complex is impaired in the kidney due to aging. Disruption of the MICOS complex shows altered mitochondrial calcium uptake and calcium retention capacity, as well as generation of oxidative stress. We found significant, detrimental structural changes to aged kidney tubule mitochondria suggesting a potential mechanism underlying why kidney diseases occur more readily with age. We hypothesize that disruption in the MICOS complex further exacerbates mitochondrial dysfunction, creating a vicious cycle of mitochondrial degradation and oxidative stress, thus impacting kidney health. Translational StatementDue to aging, the efficiency of kidney functions begins to decrease and the risk of kidney diseases may increase, but specific regulators of mitochondrial age-related changes are poorly explained. This study demonstrates the MICOS complex may be a target for mitigating age-related changes in mitochondria. The MICOS complex can be associated with oxidative stress and calcium dysregulation, which also arise in many kidney pathologies. Graphical AbstractKidney aging causes a decline in the MICOS complex, concomitant with metabolic, lipidomic, and mitochondrial structural alterations. 

Abstract “Synthetic recombinant” populations have emerged as a useful tool for dissecting the genetics of complex traits. They can be used to derive inbred lines for fine QTL mapping, or the populations themselves can be sampled for experimental evolution. In the latter application, investigators generally value maximizing genetic variation in constructed populations. This is because in evolution experiments initiated from such populations, adaptation is primarily fueled by standing genetic variation. Despite this reality, little has been done to systematically evaluate how different methods of constructing synthetic populations shape initial patterns of variation. Here we seek to address this issue by comparing outcomes in synthetic recombinant Saccharomyces cerevisiae populations created using one of two strategies: pairwise crossing of isogenic strains or simple mixing of strains in equal proportion. We also explore the impact of the varying the number of parental strains. We find that more genetic variation is initially present and maintained when population construction includes a round of pairwise crossing. As perhaps expected, we also observe that increasing the number of parental strains typically increases genetic diversity. In summary, we suggest that when constructing populations for use in evolution experiments, simply mixing founder strains in equal proportion may limit the adaptive potential. 

This article shows how mitochondria in murine cardiac changes, importantly elucidating age-related changes. It also is the first to show that the MICOS complex may play a role in outer membrane mitochondrial structure. 

Abstract Experimental evolution allows the observation of change over time as laboratory populations evolve in response to novel, controlled environments. Microbial evolution experiments take advantage of cryopreservation to archive experimental populations in glycerol media, creating a frozen, living “fossil” record. Prior research with Escherichia coli has shown that cryopreservation conditions can affect cell viability and that allele frequencies across the genome can change in response to a freeze-thaw event. We expand on these observations by characterizing fitness and genomic consequences of multiple freeze-thaw cycles in diploid yeast populations. Our study system is a highly recombinant Saccharomyces cerevisiae population (SGRP-4X) which harbors standing genetic variation that cryopreservation may threaten. We also investigate the four parental isogenic strains crossed to create the SGRP-4X. We measure cell viability over 5 consecutive freeze-thaw cycles; while we find that viability increases over time in the evolved recombinant populations, we observe no such viability improvements in the parental strains. We also collect genome-wide sequence data from experimental populations initially, after one freeze-thaw, and after five freeze-thaw cycles. In the recombinant evolved populations, we find a region of significant allele frequency change on chromosome 15 containing the ALR1 gene. In the parental strains, we find little evidence for new mutations. We conclude that cryopreserving yeast populations with standing genetic variation may have both phenotypic and genomic consequences, though these same cryopreservation practices may have only small impacts on populations with little or no initial variation. 

We present the status and plans for the Keck All sky Precision Adaptive optics (KAPA) program. KAPA includes (1) an upgrade to the Keck I laser guide star adaptive optics (AO) facility to improve image quality and sky coverage, (2) the inclusion of AO telemetry-based point spread function estimates with all science exposures, (3) four key science programs, and (4) an educational component focused on broadening the participation of women and underrepresented groups in instrumentation. For this conference we focus on the KAPA upgrades since the 2020 SPIE proceedings1 including implementation of a laser asterism generator, wavefront sensor, real-time controller, asterism and turbulence simulators, the laser tomography system itself along with new operations software and science tools, and modifications to an existing near-infrared tip-tilt sensor to support multiple natural guide star and focus measurements. We will also report on the results of daytime and on-sky calibrations and testing. 

Abstract M dwarfs are common host stars to exoplanets but often lack atmospheric abundance measurements. Late-M dwarfs are also good analogs to the youngest substellar companions, which share similarT_eff∼ 2300–2800 K. We present atmospheric analyses for the M7.5 companion HIP 55507 B and its K6V primary star with Keck/KPIC high-resolution (R∼ 35,000)K-band spectroscopy. First, by including KPIC relative radial velocities between the primary and secondary in the orbit fit, we improve the dynamical mass precision by 60% and find $M_B={88.0}_{-3.2}^{+3.4}{M}_{\mathrm{Jup}}$, putting HIP 55507 B above the stellar–substellar boundary. We also find that HIP 55507 B orbits its K6V primary star with $a={38}_{-3}^{+4}$au ande= 0.40 ± 0.04. From atmospheric retrievals of HIP 55507 B, we measure [C/H] = 0.24 ± 0.13, [O/H] = 0.15 ± 0.13, and C/O = 0.67 ± 0.04. Moreover, we strongly detect¹³CO (7.8σsignificance) and tentatively detect ${\mathrm{H}}_2^{18}\mathrm{O}$(3.7σsignificance) in the companion’s atmosphere and measure ${}^{12}\mathrm{CO}{/}^{13}\mathrm{CO}={98}_{-22}^{+28}$and ${\mathrm{H}}_2^{16}\mathrm{O}/{\mathrm{H}}_2^{18}\mathrm{O}={240}_{-80}^{+145}$after accounting for systematic errors. From a simplified retrieval analysis of HIP 55507 A, we measure ${}^{12}\mathrm{CO}{/}^{13}\mathrm{CO}={79}_{-16}^{+21}$and ${\mathrm{C}}^{16}\mathrm{O}/{\mathrm{C}}^{18}\mathrm{O}={288}_{-70}^{+125}$for the primary star. These results demonstrate that HIP 55507 A and B have consistent¹²C/¹³C and¹⁶O/¹⁸O to the <1σlevel, as expected for a chemically homogeneous binary system. Given the similar flux ratios and separations between HIP 55507 AB and systems with young substellar companions, our results open the door to systematically measuring¹³CO and ${\mathrm{H}}_2^{18}\mathrm{O}$abundances in the atmospheres of substellar or even planetary-mass companions with similar spectral types.