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The efficacy of the various pedagogies that are used in human anatomy laboratories has been extensively debated. Nevertheless, an important question remains relatively unexamined--how the learning experience in the anatomy laboratory impacts students' mastery and application of anatomical knowledge beyond the laboratory setting. In this study, the effect of a prosection-based anatomy laboratory on overall comprehension and mastery of anatomical knowledge was evaluated in an upper division undergraduate anatomy curriculum that consists of a mandatory lecture course and an optional laboratory course. This flexible curricular structure permitted assessing the merit of laboratory learning on the written examination performance of the lecture course. In 2019 and 2022, the anatomy laboratory was taught in-person using prosections, while in 2021 due to the COVID-19 pandemic related regulations, it was taught remotely with live-streaming of prosections using document cameras. In both in-person and remote instructive formats, written examination scores of the lecture course were compared between two cohorts of students: Those enrolled in lecture only and those enrolled in both lecture and laboratory. Results showed that the cohort enrolled in both lecture and laboratory courses consistently outperformed the lecture-only cohort by one full letter grade. Furthermore, when the degrees of improvement on written examination scores were compared between the two instructive formats, in-person laboratory had a greater increase compared to remote laboratory. Altogether this study demonstrates that the prosection-based anatomy laboratory enhances students' mastery of anatomical knowledge beyond the laboratory setting by promoting comprehension of spatial relationships of anatomical structures.

Aaron S. Gross, The Question of the Animal and Religion: Theoretical Stakes, Practical Implications New York: Columbia University Press, 2015, 292 pp. What is religion? Aaron S. Gross's audacious book [...]

Global warming is amplified in the Arctic. However, numerical models struggle to represent key processes that determine Arctic weather and climate. To collect data that help to constrain the models, the HALO–(𝒜𝒞)3 aircraft campaign was conducted over the Norwegian and Greenland seas, the Fram Strait, and the central Arctic Ocean in March and April 2022. The campaign focused on one specific challenge posed by the models, namely the reasonable representation of transformations of air masses during their meridional transport into and out of the Arctic via northward moist- and warm-air intrusions (WAIs) and southward marine cold-air outbreaks (CAOs). Observations were made over areas of open ocean, the marginal sea ice zone, and the central Arctic sea ice. Two low-flying and one long-range, high-altitude research aircraft were flown in colocated formation whenever possible. To follow the air mass transformations, a quasi-Lagrangian flight strategy using trajectory calculations was realized, enabling us to sample the same moving-air parcels twice along their trajectories. Seven distinct WAI and 12 CAO cases were probed. From the quasi-Lagrangian measurements, we have quantified the diabatic heating/cooling and moistening/drying of the transported air masses. During CAOs, maximum values of 3 K h−1 warming and 0.3 g kg−1 h−1 moistening were obtained below 1 km altitude. From the observations of WAIs, diabatic cooling rates of up to 0.4 K h−1 and a moisture loss of up to 0.1 g kg−1 h−1 from the ground to about 5.5 km altitude were derived. Furthermore, the development of cloud macrophysical (cloud-top height and horizontal cloud cover) and microphysical (liquid water path, precipitation, and ice index) properties along the southward pathways of the air masses were documented during CAOs, and the moisture budget during a specific WAI event was estimated. In addition, we discuss the statistical frequency of occurrence of the different thermodynamic phases of Arctic low-level clouds, the interaction of Arctic cirrus clouds with sea ice and water vapor, and the characteristics of microphysical and chemical properties of Arctic aerosol particles. Finally, we provide a proof of concept to measure mesoscale divergence and subsidence in the Arctic using data from dropsondes released during the flights.

Mixed-phase clouds are not well represented in climate and weather forecasting models, due to a lack of the key processes controlling their life cycle. Developing methods to study these clouds is therefore essential, despite the complexity of mixed-phase cloud processes and the difficulty of observing two cloud phases simultaneously. We propose in this paper a new method to retrieve the microphysical properties of mixed-phase clouds, ice clouds and supercooled water clouds using airborne or satellite radar and lidar measurements, called VarPy-mix. This new approach extends an existing variational method developed for ice cloud retrieval using lidar, radar and passive radiometers. We assume that the lidar attenuated backscatter β at 532 nm is more sensitive to particle concentration and is consequently mainly sensitive to the presence of supercooled water. In addition, radar reflectivity Z at 95 GHz is sensitive to the size of hydrometeors and hence more sensitive to the presence of ice particles. Consequently, in the mixed phase the supercooled droplets are retrieved with the lidar signal and the ice particles with the radar signal, meaning that the retrievals rely strongly on a priori and error values. This method retrieves simultaneously the visible extinction for ice αice and liquid αliq particles, the ice and liquid water contents IWC and LWC, the effective radius of ice re,ice and liquid re,liq particles, and the ice and liquid number concentrations Nice and Nliq. Moreover, total extinction αtot, total water content (TWC) and total number concentration Ntot can also be estimated. As the retrieval of ice and liquid is different, it is necessary to correctly identify each phase of the cloud. To this end, a cloud-phase classification is used as input to the algorithm and has been adapted for mixed-phase retrieval. The data used in this study are from DARDAR-MASK v2.23 products, based on the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) and Cloud Profiling Radar (CPR) observations from the CALIPSO and CloudSat satellites, respectively, belonging to the A-Train constellation launched in 2006. Airborne in situ measurements performed on 7 April 2007 during the Arctic Study of Tropospheric Aerosol, Clouds and Radiation (ASTAR) campaign and collected under the track of CloudSat–CALIPSO are compared with the retrievals of the new algorithm to validate its performance. Visible extinctions, water contents, effective radii and number concentrations derived from in situ measurements and the retrievals showed similar trends and are globally in good agreement. The mean percent error between the retrievals and in situ measurements is 39 % for αliq, 398 % for αice, 49 % for LWC and 75 % for IWC. It is also important to note that temporal and spatial collocations are not perfect, with a maximum spatial shift of 1.68 km and a maximum temporal shift of about 10 min between the two platforms. In addition, the sensitivity of remote sensing and that of in situ measurements is not the same, and in situ measurement uncertainties are between 25 % and 60 %.

In insects and mammals, 3D genome topology has been linked to transcriptional states yet whether this link holds for other eukaryotes is unclear. Using both ligation proximity and fluorescence microscopy assays, we show that in Saccharomyces cerevisiae, Heat Shock Response (HSR) genes dispersed across multiple chromosomes and under the control of Heat Shock Factor (Hsf1) rapidly reposition in cells exposed to acute ethanol stress and engage in concerted, Hsf1-dependent intergenic interactions. Accompanying 3D genome reconfiguration is equally rapid formation of Hsf1-containing condensates. However, in contrast to the transience of Hsf1-driven intergenic interactions that peak within 10–20 min and dissipate within 1 hr in the presence of 8.5% (v/v) ethanol, transcriptional condensates are stably maintained for hours. Moreover, under the same conditions, Pol II occupancy of HSR genes, chromatin remodeling, and RNA expression are detectable only later in the response and peak much later (>1 hr). This contrasts with the coordinate response of HSR genes to thermal stress (39°C) where Pol II occupancy, transcription, histone eviction, intergenic interactions, and formation of Hsf1 condensates are all rapid yet transient (peak within 2.5–10 min and dissipate within 1 hr). Therefore, Hsf1 forms condensates, restructures the genome and transcriptionally activates HSR genes in response to both forms of proteotoxic stress but does so with strikingly different kinetics. In cells subjected to ethanol stress, Hsf1 forms condensates and repositions target genes before transcriptionally activating them.

Warm-air intrusions (WAIs) are responsible for the transportation of warm and moist air masses from the mid-latitudes into the high Arctic (> 70° N). In this work, we study cirrus clouds that form during WAI events (WAI cirrus) and during undisturbed Arctic conditions (AC cirrus) and investigate possible differences between the two cloud types based on their macrophysical and optical properties with a focus on relative humidity over ice (RHi). We use airborne measurements from the combined high-spectral-resolution and differential-absorption lidar, WALES, performed during the HALO-(AC)3 campaign. We classify each research flight and the measured clouds as either AC or WAI, based on the ambient conditions, and study the macrophysical, geometrical and optical characteristics for each cirrus group. As our main parameter we choose the relative humidity over ice (RHi), which we calculate RHi by combining the lidar water vapor measurements with model temperatures. Ice formation occurs at certain RHi values depending on the dominant nucleation process taking place. RHi can thus be used as an indication of the nucleation process and the structure of cirrus clouds. We find that during WAI events the Arctic is warmer and moister and WAI cirrus clouds are both geometrically and optically thicker compared to AC cirrus. WAI cirrus clouds and the layer directly surrounding them are more frequently supersaturated, also at high supersaturations over the threshold for homogeneous ice nucleation (HOM). AC cirrus clouds have a supersaturation-dominated cloud top and a subsaturated cloud base. WAI cirrus clouds also have high supersaturations at cloud top but also at cloud base.

Abstract Background Heterotopic ossification (HO) is a frequent and debilitating complication of traumatic musculoskeletal injuries and orthopedic procedures. Prophylactic dosing of botulinum toxin type A (BTxA) holds potential as a novel treatment option if accurately distributed throughout soft-tissue volumes where protection is clinically desired. We developed a high-resolution, microcomputed tomography (microCT)-based imaging strategy to assess drug distribution and validated this platform by quantifying distribution achieved via a prototype delivery system versus a single-bolus injection. Methods We injected an iodine-containing contrast agent (iodixanol 320 mg I/mL) into dissected rabbit musculature followed by microCT imaging and analysis. To contrast the performance of distributed versus bolus injections, a three-dimensional (3D) 64-cm3-printed soft-tissue holder was developed. A centered 2-cm3 volume of interest (VOI) was targeted with a single-bolus injection or an equal volume distributed injection delivered via a 3D-printed prototype. VOI drug coverage was quantified as a percentage of the VOI volume that was < 1.0 mm from the injected fluid. Results The microCT-based approach enabled high-resolution quantification of injection distribution within soft tissue. The distributed dosing prototype provided significantly greater tissue coverage of the targeted VOI (72 ± 3%, mean ± standard deviation) when compared to an equal volume bolus dose (43 ± 5%, p = 0.031) while also enhancing the precision of injection targeting. Conclusions A microCT-based imaging technique precisely quantifies drug distribution within a soft-tissue VOI, providing a path to overcome a barrier for clinical translation of prophylactic inhibition of HO by BTxA. Relevance statement This platform will facilitate rapid optimization of injection parameters for clinical devices used to effectively and safely inhibit the formation of heterotopic ossification. Key points • MicroCT provides high-resolution quantification of soft-tissue drug distribution. • Distributed dosing is required to maximize soft-tissue drug coverage. • Imaging platform will enable rapid screening of 3D-printed drug distribution prototypes. Graphical Abstract

Aviation has a large impact on the Earth's atmosphere and climate by various processes. Line-shaped contrails and contrail cirrus clouds lead to changes in the natural cirrus cloud cover and have a major contribution to the effective radiative forcing from aviation. In addition, aviation-induced aerosols might also change the microphysical properties and optical properties of naturally formed cirrus clouds. Latter aerosol–cloud interactions show large differences in the resulting effective radiative forcing, and our understanding on how aviation-induced aerosols affect cirrus cloud properties is still poor. Up to now, observations of this aviation-induced aerosol effect have been rare. In this study, we use combined airborne lidar and in situ ice cloud measurements to investigate differences in the microphysical and optical properties of naturally formed cirrus clouds, which formed in regions that are highly affected by aviation-induced aerosol emissions and, of those, which formed in regions rather unaffected by aviation. Urbanek et al. (2018) showed that those cirrus clouds, which are more affected by aviation-induced soot emission, are characterized by larger values of the particle linear depolarization ratio (PLDR). In this follow-on study we relate collocated lidar measurements performed aboard HALO during the ML-CIRRUS mission of the particle linear depolarization ratio with in situ cloud probe measurements of the number concentration and effective diameter of the ice particles. In situ measurements for both cloud types (high-PLDR-mode – aviation-affected – and low-PLDR-mode – pristine – cirrus) can be reliably compared in a temperature range between 210 and 215 K. Within this temperature range we find that high-PLDR-mode cirrus clouds tend to show larger effective ice particle diameters with a median value of 61.4 compared to 50.7 µm for low-PLDR-mode pristine cirrus clouds. Larger effective ice particles in aviation-influenced (high-PLDR-mode) cirrus are connected to lower ice particle number concentration with a median value of 0.05 compared to 0.11 cm−3 (low-PLDR-mode), which evolved in more pristine regions with only little impact from aviation. We suspect that a suppression of homogeneous ice formation by the heterogeneously freezing soot aerosol particles included in the areas affected by air traffic is the cause of the reduced ice crystal concentrations.

Abstract Numerous factors influence the timing of spring migration in birds, yet the relative importance of intrinsic and extrinsic variables on migration initiation remains unclear. To test for interactions among weather, migration distance, parasitism, and physiology in determining spring departure date, we used the Dark‐eyed Junco (Junco hyemalis) as a model migratory species known to harbor diverse and common haemosporidian parasites. Prior to spring migration departure from their wintering grounds in Indiana, USA, we quantified the intrinsic variables of fat, body condition (i.e., mass ~ tarsus residuals), physiological stress (i.e., ratio of heterophils to lymphocytes), cellular immunity (i.e., leukocyte composition and total count), migration distance (i.e., distance to the breeding grounds) using stable isotopes of hydrogen from feathers, and haemosporidian parasite intensity. We then attached nanotags to determine the timing of spring migration departure date using the Motus Wildlife Tracking System. We used additive Cox proportional hazard mixed models to test how risk of spring migratory departure was predicted by the combined intrinsic measures, along with meteorological predictors on the evening of departure (i.e., average wind speed and direction, relative humidity, and temperature). Model comparisons found that the best predictor of spring departure date was average nightly wind direction and a principal component combining relative humidity and temperature. Juncos were more likely to depart for spring migration on nights with largely southwestern winds and on warmer and drier evenings (relative to cooler and more humid evenings). Our results indicate that weather conditions at take‐off are more critical to departure decisions than the measured physiological and parasitism variables.

Abstract Mitochondrial diseases are a heterogeneous group of monogenic disorders that result from impaired oxidative phosphorylation (OXPHOS). As neuromuscular tissues are highly energy‐dependent, mitochondrial diseases often affect skeletal muscle. Although genetic and bioenergetic causes of OXPHOS impairment in human mitochondrial myopathies are well established, there is a limited understanding of metabolic drivers of muscle degeneration. This knowledge gap contributes to the lack of effective treatments for these disorders. Here, we discovered fundamental muscle metabolic remodeling mechanisms shared by mitochondrial disease patients and a mouse model of mitochondrial myopathy. This metabolic remodeling is triggered by a starvation‐like response that evokes accelerated oxidation of amino acids through a truncated Krebs cycle. While initially adaptive, this response evolves in an integrated multiorgan catabolic signaling, lipid store mobilization, and intramuscular lipid accumulation. We show that this multiorgan feed‐forward metabolic response involves leptin and glucocorticoid signaling. This study elucidates systemic metabolic dyshomeostasis mechanisms that underlie human mitochondrial myopathies and identifies potential new targets for metabolic intervention.

Abstract Genetically engineered mouse models (GEMMs) are important immunocompetent models for research into the roles of individual genes in cancer and the development of novel therapies. Here we use inducible CRISPR-Cas9 systems to develop two GEMMs which aim to model the extensive chromosome p3 deletion frequently observed in clear cell renal cell carcinoma (ccRCC). We cloned paired guide RNAs targeting early exons of Bap1, Pbrm1, and Setd2 in a construct containing a Cas9D10A (nickase, hSpCsn1n) driven by tetracycline (tet)-responsive elements (TRE3G) to develop our first GEMM. The founder mouse was crossed with two previously established transgenic lines, one carrying the tet-transactivator (tTA, Tet-Off) and one with a triple-mutant stabilized HIF1A-M3 (TRAnsgenic Cancer of the Kidney, TRACK), both driven by a truncated, proximal tubule-specific γ-glutamyltransferase 1 (ggt or γGT) promoter, to create triple-transgenic animals. Our results indicate that this model (BPS-TA) induces low numbers of somatic mutations in Bap1 and Pbrm1 (but not in Setd2), known tumor suppressor genes in human ccRCC. These mutations, largely restricted to kidneys and testis, induced no detectable tissue transformation in a cohort of 13 month old mice (N = 10). To gain insights into the low frequencies of insertions and deletions (indels) in BPS-TA mice we analyzed wild type (WT, N = 7) and BPS-TA (N = 4) kidneys by RNAseq. This showed activation of both DNA damage and immune response, suggesting activation of tumor suppressive mechanisms in response to genome editing. We then modified our approach by generating a second model in which a ggt-driven, cre-regulated Cas9WT(hSpCsn1) was employed to introduce Bap1, Pbrm1, and Setd2 genome edits in the TRACK line (BPS-Cre). The BPS-TA and BPS-Cre lines are both tightly controlled in a spatiotemporal manner with doxycycline (dox) and tamoxifen (tam), respectively. In addition, whereas the BPS-TA line relies on paired guide RNAs (gRNAs), the BPS-Cre line requires only single gRNAs for gene perturbation. In the BPS-Cre we identified increased Pbrm1 gene-editing frequencies compared to the BPS-TA model. Whereas we did not detect Setd2 edits in the BPS-TA kidneys, we found extensive editing of Setd2 in the BPS-Cre model. Bap1 editing efficiencies were comparable between the two models. Although no gross malignancies were observed in our study, this is the first reported GEMM which models the extensive chromosome 3p deletion frequently observed in kidney cancer patients. Further studies are required (1) to model more extensive 3p deletions, e.g. impacting additional genes, and (2) to increase the cellular resolution, e.g. by employing single-cell RNAseq to ascertain the effects of specific combinatorial gene inactivation.

Resolving the orbital structure of single atoms is challenging and of great importance for understanding basic chemistry. Here, the authors demonstrate that the orbital occupation difference of single Fe/Co atoms within molecules can be distinguished with high resolution AFM imaging and spectroscopy.

Water vapor measurements of midlatitude cirrus clouds, obtained by the WAter vapour Lidar Experiment in Space (WALES) lidar system during the Mid-Latitude Cirrus (ML-CIRRUS) airborne campaign, which took place in the spring of 2014 over central Europe and the NE Atlantic Ocean, are combined with model temperatures from the European Centre for Medium-Range Weather Forecasts (ECMWF) and analyzed. Our main focus is to derive the distribution and temporal evolution of humidity with respect to ice within cirrus clouds and in their adjacent cloud-free air. We find that 34.1 % of in-cloud data points are supersaturated with respect to ice. Supersaturation is also detected in 6.8 % of the cloud-free data points. When the probability density of the relative humidity over ice (RHi) is calculated with respect to temperature for the in-cloud data points from the ML-CIRRUS dataset, there are two peaks: one around 225 K and close to saturation, RHi = 100 %, and a second one at colder temperatures around 218 K in subsaturation, RHi = 79 %. These two regions seem to represent two cirrus cloud categories: in situ formed and liquid origin. Regarding their vertical structure, most clouds have higher supersaturations close to the cloud top and become subsaturated near the cloud bottom. Finally, we find that the vertical structure of RHi within the clouds is also indicative of their life stage. RHi skewness tends to go from positive to negative values as the cloud ages. RHi modes are close to saturation in young clouds, supersaturated in mature clouds and subsaturated in dissipating clouds.