Transiently silencing genes associated with voluntary physical activity using intravenous injection of Vivo‐morpholinos

Physical inactivity has been associated with several diseases and conditions with multiple candidate genes proposed to regulate voluntary physical activity. However, there has not been a reliable method to silence candidate genes in vivo to determine causal mechanisms of physical activity regulation. The novel molecular biology tool, Vivo‐morpholinos, is a potential method to transiently silence specific genes. Thus, the aim of this study was to validate the use of Vivo‐morpholinos in a mouse model for voluntary physical activity with several sub‐objectives. We observed that Vivomorpholinos achieved between 60 – 97% knockdown of Drd1‐, Vmat2‐, and Glut4‐protein in skeletal muscle, the delivery moiety of Vivo‐morpholinos (scramble) did not influence physical activity and that a cocktail of multiple Vivo‐morpholinos can be given in a single treatment to achieve protein knockdown of two different targeted proteins in skeletal muscle simultaneously. Knocking down Drd1, Vmat2, or Glut4 protein in skeletal muscle did not affect physical activity. Vivo‐morpholinos injected intravenously alone did not significantly knockdown Vmat2‐protein expression in the brain (p=0.28). However, the use of a bradykinin analog to increase blood‐brain‐barrier permeability in conjunction with the Vivomorpholinos significantly (p=0.0001) decreased Vmat2‐protein in the brain with a corresponding later over‐expression of Vmat2 coincident with a significant (p=0.0016) increase in physical activity. We conclude that with appropriate research design, Vivo‐morpholinos can be a valuable tool in determining causal gene‐phenotype relationships in whole animal models

Stepping Stones: A Leadership Development Program to Inspire and Promote Reflection Among Women Faculty and Staff

Women frequently benefit from focused faculty development opportunities not because they need to be “fixed,” but rather it is a means to demonstrate that success, even in chilly environments, is possible. The Stepping Stones program uses a unique design to provide participants with inspiration, time for reflection, and strategies for how to navigate one's career, through hearing about the journeys of successful women. In this article, we describe the program and evaluation results. Post‐event and longitudinal follow‐up surveys indicate that the program and its unique narrative format help to debunk the superwoman myth and leave participants with a sense of optimism about their future careers

Comparative population genomics of latitudinal variation in \u3ci\u3eDrosophila simulans\u3c/i\u3e and \u3ci\u3eDrosophila melanogaster\u3c/i\u3e

Examples of clinal variation in phenotypes and genotypes across latitudinal transects have served as important models for understanding how spatially varying selection and demographic forces shape variation within species. Here, we examine the selective and demographic contributions to latitudinal variation through the largest comparative genomic study to date of Drosophila simulans and Drosophila melanogaster, with genomic sequence data from 382 individual fruit flies, collected across a spatial transect of 19 degrees latitude and at multiple time points over 2 years. Consistent with phenotypic studies, we find less clinal variation in D. simulans than D. melanogaster, particularly for the autosomes. Moreover, we find that clinally varying loci in D. simulans are less stable over multiple years than comparable clines in D. melanogaster. D. simulans shows a significantly weaker pattern of isolation by distance than D. melanogaster and we find evidence for a stronger contribution of migration to D. simulans population genetic structure. While population bottlenecks and migration can plausibly explain the differences in stability of clinal variation between the two species, we also observe a significant enrichment of shared clinal genes, suggesting that the selective forces associated with climate are acting on the same genes and phenotypes in D. simulans and D. melanogaster. Includes supplementary materials

Comparative population genomics of latitudinal variation in \u3ci\u3eDrosophila simulans\u3c/i\u3e and \u3ci\u3eDrosophila melanogaster\u3c/i\u3e

Examples of clinal variation in phenotypes and genotypes across latitudinal transects have served as important models for understanding how spatially varying selection and demographic forces shape variation within species. Here, we examine the selective and demographic contributions to latitudinal variation through the largest comparative genomic study to date of Drosophila simulans and Drosophila melanogaster, with genomic sequence data from 382 individual fruit flies, collected across a spatial transect of 19 degrees latitude and at multiple time points over 2 years. Consistent with phenotypic studies, we find less clinal variation in D. simulans than D. melanogaster, particularly for the autosomes. Moreover, we find that clinally varying loci in D. simulans are less stable over multiple years than comparable clines in D. melanogaster. D. simulans shows a significantly weaker pattern of isolation by distance than D. melanogaster and we find evidence for a stronger contribution of migration to D. simulans population genetic structure. While population bottlenecks and migration can plausibly explain the differences in stability of clinal variation between the two species, we also observe a significant enrichment of shared clinal genes, suggesting that the selective forces associated with climate are acting on the same genes and phenotypes in D. simulans and D. melanogaster. Includes supplementary materials

Warming and elevated CO2 promote rapid incorporation and degradation of plant-derived organic matter in an ombrotrophic peatland

Rising temperatures have the potential to directly affect carbon cycling in peatlands by enhancing organic matter (OM) decomposition, contributing to the release of CO2 and CH4 to the atmosphere. In turn, increasing atmospheric CO2 concentration may stimulate photosynthesis, potentially increasing plant litter inputs belowground and transferring carbon from the atmosphere into terrestrial ecosystems. Key questions remain about the magnitude and rate of these interacting and opposing environmental change drivers. Here, we assess the incorporation and degradation of plant- and microbe-derived OM in an ombrotrophic peatland after 4 years of whole-ecosystem warming (+0, +2.25, +4.5, +6.75 and +9°C) and two years of elevated CO2 manipulation (500 ppm above ambient). We show that OM molecular composition was substantially altered in the aerobic acrotelm, highlighting the sensitivity of acrotelm carbon to rising temperatures and atmospheric CO2 concentration. While warming accelerated OM decomposition under ambient CO2, new carbon incorporation into peat increased in warming × elevated CO2 treatments for both plant- and microbe-derived OM. Using the isotopic signature of the applied CO2 enrichment as a label for recently photosynthesized OM, our data demonstrate that new plant inputs have been rapidly incorporated into peat carbon. Our results suggest that under current hydrological conditions, rising temperatures and atmospheric CO2 levels will likely offset each other in boreal peatlands

Rewiring the Sex-Determination Pathway During the Evolution of Self-Fertility.

Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The TRA-2 domain that mediates contact with TRA-1 is conserved in Caenorhabditis. By comparing the interaction of these proteins in two species, we identified a striking change in how sexual development is controlled. Identical mutations in this domain promote oogenesis in Caenorhabditis elegans but promote spermatogenesis in Caenorhabditis briggsae. Furthermore, the effects of these mutations involve the male-promoting gene fem-3 in C. elegans but are independent of fem-3 in C. briggsae. Finally, reciprocal mutations in these genes show that C. briggsae TRA-2 binds TRA-1 to prevent expression of spermatogenesis regulators. By contrast, in C. elegans TRA-1 sequesters TRA-2 in the germ line, allowing FEM-3 to initiate spermatogenesis. Thus, we propose that the flow of information within the sex determination pathway has switched directions during evolution. This result has important implications for how evolutionary change can occur

Novel M4 Pediatrics Chief Program Utilizing Near-peer Teaching and Mentoring to Enhance Clerkship Curricula

Introduction: Near-peer teachers add many benefits to the academic, clinical performance, and enjoyment of near-peer learners in medical education. This enterprise describes and examines how the Creighton University School of Medicine M4 Pediatrics Chief Program fills a gap in medical education by offering an organized and formal methodology for near-peer teaching. The Creighton University M4 Pediatrics Chief Program utilizes select fourth year medical students to orient, teach basic clinical skills, mentor, and participate in curriculum development for the third year Pediatric clerkship students. Methods: Third year students (n=43) in their Pediatrics clerkship from September 2020 to February 2021 completed surveys at the end of the clerkship to assess the quality and effectiveness of the M4 Pediatrics Chief Program. Results: Students rated effectiveness of the Chiefs most highly as clerkship guides (4.29, SD=0.79), teachers (4.21, SD=0.92), and mentors (4.19, SD=0.75). Near-peer perspectives, education, provision of pertinent content, serving as a clerkship resource, and being a source of encouragement were the most beneficial aspects of the program. Students reported strong agreement all clerkships should have an M4 Chief Program (4.53, SD=0.88). Discussion: Because of the positive reviews by the third years students, the M4 Pediatrics Chief Program is now a permanent part of the Pediatric Clerkship. Additionally, other third year clerkships at Creighton University School of Medicine are adopting this model. Finally, the M4 students acting as the chiefs gain valuable leadership and educational skills. Conclusion: Based on positive perceptions of the “M4 Chief Program”, the authors recommend other medical schools consider initiating similar programs within their third year clerkships.https://digitalcommons.unmc.edu/chri_forum/1037/thumbnail.jp

Spectroscopic Discovery of the Broad-Lined Type Ic Supernova 2010bh Associated with the Low-Redshift GRB 100316D

We present the spectroscopic discovery of a broad-lined Type Ic supernova (SN 2010bh) associated with the nearby long-duration gamma-ray burst (GRB) 100316D. At z = 0.0593, this is the third-nearest GRB-SN. Nightly optical spectra obtained with the Magellan telescopes during the first week after explosion reveal the gradual emergence of very broad spectral features superposed on a blue continuum. The supernova features are typical of broad-lined SNe Ic and are generally consistent with previous supernovae associated with low-redshift GRBs. However, the inferred velocities of SN 2010bh at 21 days after explosion are a factor of ~2 times larger than those of the prototypical SN 1998bw at similar epochs, with v ~ 26,000 km/s, indicating a larger explosion energy or a different ejecta structure. A near-infrared spectrum taken 13.8 days after explosion shows no strong evidence for He I at 1.083 microns, implying that the progenitor was largely stripped of its helium envelope. The host galaxy is of low luminosity (M_R ~ -18.5 mag) and low metallicity (Z < 0.4 Z_solar), similar to the hosts of other low-redshift GRB-SNe.Comment: 6 pages, 4 figures, 1 table, submitted to ApJ Letter

Whole-soil warming decreases abundance and modifies the community structure of microorganisms in the subsoil but not in surface soil

The microbial community composition in subsoils remains understudied, and it is largely unknown whether subsoil microorganisms show a similar response to global warming as microorganisms at the soil surface do. Since microorganisms are the key drivers of soil organic carbon decomposition, this knowledge gap causes uncertainty in the predictions of future carbon cycling in the subsoil carbon pool (> 50 % of the soil organic carbon stocks are below 30 cm soil depth). In the Blodgett Forest field warming experiment (California, USA) we investigated how +4 ∘C warming in the whole-soil profile to 100 cm soil depth for 4.5 years has affected the abundance and community structure of microorganisms. We used proxies for bulk microbial biomass carbon (MBC) and functional microbial groups based on lipid biomarkers, such as phospholipid fatty acids (PLFAs) and branched glycerol dialkyl glycerol tetraethers (brGDGTs). With depth, the microbial biomass decreased and the community composition changed. Our results show that the concentration of PLFAs decreased with warming in the subsoil (below 30 cm) by 28 % but was not affected in the topsoil. Phospholipid fatty acid concentrations changed in concert with soil organic carbon. The microbial community response to warming was depth dependent. The relative abundance of Actinobacteria increased in warmed subsoil, and Gram+ bacteria in subsoils adapted their cell membrane structure to warming-induced stress, as indicated by the ratio of anteiso to iso branched PLFAs. Our results show for the first time that subsoil microorganisms can be more affected by warming compared to topsoil microorganisms. These microbial responses could be explained by the observed decrease in subsoil organic carbon concentrations in the warmed plots. A decrease in microbial abundance in warmed subsoils might reduce the magnitude of the respiration response over time. The shift in the subsoil microbial community towards more Actinobacteria might disproportionately enhance the degradation of previously stable subsoil carbon, as this group is able to metabolize complex carbon sources

2MASSJ035523.51+113337.4: A Young, Dusty, Nearby, Isolated Brown Dwarf Resembling A Giant Exoplanet

We present parallax and proper motion measurements, near-infrared spectra, and WISE photometry for the low surface gravity L5gamma dwarf 2MASSJ035523.37+113343.7 (2M0355). We use these data to evaluate photometric, spectral, and kinematic signatures of youth as 2M0355 is the reddest isolated L dwarf yet classified. We confirm its low-gravity spectral morphology and find a strong resemblance to the sharp triangular shaped $H$-band spectrum of the 10 Myr planetary-mass object 2M1207b. We find that 2M0355 is underluminous compared to a normal field L5 dwarf in the optical and MKO J,H, and K bands and transitions to being overluminous from 3-12 microns, indicating that enhanced photospheric dust shifts flux to longer wavelengths for young, low-gravity objects, creating a red spectral energy distribution. Investigating the near-infrared color magnitude diagram for brown dwarfs confirms that 2M0355 is redder and underluminous compared to the known brown dwarf population, similar to the peculiarities of directly imaged exoplanets 2M1207b and HR8799bcd. We calculate UVW space velocities and find that the motion of 2M0355 is consistent with young disk objects (< 2-3 Gyr) and it shows a high likelihood of membership in the AB Doradus association.Comment: 23 pages, 10 figures, 5 Tables, Submitted to AJ 13 May 201