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The contribution of pre-mRNA processing mechanisms to the regulation of immune responses remains poorly studied despite emerging examples of their role as regulators of immune defenses. We sought to investigate the role of mRNA processing in the cellular responses of human macrophages to live bacterial infections. Here, we used mRNA sequencing to quantify gene expression and isoform abundances in primary macrophages from 60 individuals, before and after infection with Listeria monocytogenes and Salmonella typhimurium. In response to both bacteria we identified thousands of genes that significantly change isoform usage in response to infection, characterized by an overall increase in isoform diversity after infection. In response to both bacteria, we found global shifts towards (i) the inclusion of cassette exons and (ii) shorter 3' UTRs, with near-universal shifts towards usage of more upstream polyadenylation sites. Using complementary data collected in non-human primates, we show that these features are evolutionarily conserved among primates. Following infection, we identify candidate RNA processing factors whose expression is associated with individual-specific variation in isoform abundance. Finally, by profiling microRNA levels, we show that 3' UTRs with reduced abundance after infection are significantly enriched for target sites for particular miRNAs. These results suggest that the pervasive usage of shorter 3' UTRs is a mechanism for particular genes to evade repression by immune-activated miRNAs. Collectively, our results suggest that dynamic changes in RNA processing may play key roles in the regulation of innate immune responses.

In Heliconius butterflies, wing colour pattern diversity and scale types are controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation. One of these genes, cortex , has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knockouts in multiple Heliconius species and show that cortex is a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identified cis -regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In the H. melpomene/timareta lineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting that cis -regulatory structural variation underlies these mimetic adaptations. Our work shows that cortex functionally controls scale colour fate and that its cis -regulatory regions control a phenotypic switch in a modular and pattern-specific fashion. Heliconius butterflies have bright patterns on their wings that tell potential predators that they are toxic. As a result, predators learn to avoid eating them. Over time, unrelated species of butterflies have evolved similar patterns to avoid predation through a process known as Müllerian mimicry. Worldwide, there are over 180,000 species of butterflies and moths, most of which have different wing patterns. How do genes create this pattern diversity? And do butterflies use similar genes to create similar wing patterns? One of the genes involved in creating wing patterns is called cortex . This gene has a large region of DNA around it that does not code for proteins, but instead, controls whether cortex is on or off in different parts of the wing. Changes in this non-coding region can act like switches, turning regions of the wing into different colours and creating complex patterns, but it is unclear how these switches have evolved. Butterfly wings get their colour from tiny structures called scales, which each have their own unique set of pigments. In Heliconius butterflies, there are three types of scales: yellow/white scales, black scales, and red/orange/brown scales. Livraghi et al. used a DNA editing technique called CRISPR to find out whether the cortex gene affects scale type. First, Livraghi et al. confirmed that deleting cortex turned black and red scales yellow. Next, they used the same technique to manipulate the non-coding DNA around the cortex gene to see the effect on the wing pattern. This manipulation turned a black-winged butterfly into a butterfly with a yellow wing band, a pattern that occurs naturally in Heliconius butterflies. The next step was to find the mutation responsible for the appearance of yellow wing bands in nature. It turns out that a bit of extra genetic code, derived from so-called ‘jumping genes’, had inserted itself into the non-coding DNA around the cortex gene, ‘flipping’ the switch and leading to the appearance of the yellow scales. Genetic information contains the instructions to generate shape and form in most organisms. These instructions evolve over millions of years, creating everything from bacteria to blue whales. Butterfly wings are visual evidence of evolution, but the way their genes create new patterns isn't specific to butterflies. Understanding wing patterns can help researchers to learn how genetic switches control diversity across other species too.

Cuvier’s beaked whales Ziphius cavirostris are wide-ranging, deep-diving cetaceans that are particularly sensitive to anthropogenic noise. Current stock assessments assume a single population in the western North Atlantic Ocean, but knowledge of the residency patterns and distribution of the species is currently lacking in the region. Here we describe the spatial ecology of 20 Cuvier’s beaked whales equipped with satellite-linked tags off Cape Hatteras, North Carolina, USA, between 2014 and 2017. We applied a hierarchical switching state-space model to filter location estimates and define behavioral states of area-restricted search (ARS) and transit. We used kernel density estimation to identify high use areas, and net squared displacement analyses to assess residency. The vast majority (96%) of locations were classified as ARS behavior, suggesting that tagged whales allocated much of their time to foraging. Maximum net displacement had a sample median of 50 km, and 81% of individual whales were classified as demonstrating a resident, or ‘home range,’ movement pattern. Overall, our research indicates a localized population of Cuvier’s beaked whales occupying the area off Cape Hatteras. The tagged animals demonstrated a small, defined core use area and exhibited little displacement from the region. These patterns of movement and spatial use can inform future conservation and management of this species, which is vulnerable to anthropogenic disturbances caused by several sources, including mid-frequency active sonar and seismic exploration.

Background Animal-borne telemetry instruments (tags) have greatly advanced our understanding of species that are challenging to observe. Recently, non-recoverable instruments attached to cetaceans have increased in use, but these devices have limitations in data transmission bandwidth. We analyze trade-offs in the longevity, resolution, and continuity of data records from non-recoverable satellite-linked tags on deep-diving Ziphius cavirostris in the context of a behavioral response study of acute noise exposure. We present one data collection programming scheme that balances resolution and continuity against longevity to address specific questions about the behavioral responses of animals to noise exposure in experimental contexts. We compare outputs between two programming regimes on a commercially available satellite-linked tag: (1) dive behavior summary defined by conductivity thresholds and (2) depth time-series at various temporal resolutions. Results We found that time-series data vary from the more precisely defined dives from a dive summary record data stream by an acceptable error range for our application. We determined a 5-min time-series data stream collected for 14 days balanced resolution with longevity, achieving complete or nearly complete diving records in 6 out of 8 deployments. We increased our data message reception rate several fold by employing a boat based data capture system. Finally, a tag deployed in a group concurrently with a high-resolution depth recorder showed high depth concordance. Conclusions We present the conceptual framework and iterative process for matching telemetry tag programming to research questions that we used and which should be applicable to a wide range of studies. Although designing new hardware for our specific questions was not feasible at the time, we were able to optimize the sampling regime of a commercially available instrument to meet the needs of our research questions and proposed analyses. Nevertheless, for other study species or designs, the complicated intersection between animal behavior and bandwidth of telemetry systems can often create a severe mismatch among research questions, data collection, and analysis tools. More flexible programming and purpose-built instruments will increase the efficacy of these studies and increase the scientific yield relative to the inherently higher risk of invasive studies.

Shelf break systems are ecologically important regions of the ocean, and are often characterized by enhanced productivity and high densities of species from lower to upper trophic levels. Along with associated submarine canyons, shelf break regions provide important foraging habitat for deep-diving odontocetes such as pilot whales. Short-finned pilot whales Globicephala macrorhynchus are found throughout tropical and subtropical waters, but there is little information on the habitat use of this species in the northwest Atlantic. We examined the movements and foraging behavior of short-finned pilot whales using data from satellite tags (n = 33) deployed off Cape Hatteras, North Carolina, USA in 2014 and 2015. Pilot whale tracks ranged from Cape Lookout, North Carolina north to Georges Bank, with movements and habitat use primarily focused north of Cape Hatteras. We observed 2 distinct modes of behavior, with most pilot whales showing a strong affinity for the continental shelf break and others following offshore meanders of the Gulf Stream for all or part of the observed track. We used first passage time (FPT) to assess area-restricted search behavior, and found that FPT was significantly higher close to the shelf break and in submarine canyons. Our results demonstrate the importance of steep bathymetric features to the foraging habitat and distribution of short-finned pilot whales in this region. In addition, our findings suggest that pilot whales in the Mid-Atlantic Bight may have developed specialized foraging behaviors for targeting steep bathymetric gradients, and that their latitudinal distribution may be limited to regions where this foraging strategy is effective.

Background: Personal and professional biases can affect decision-making regarding important issues in pediatric sports medicine. Gaining insight into the opinions of health care professionals who specialize in pediatric sports medicine will provide information that may be useful for directing ongoing research in this field. Hypothesis: It was hypothesized that surgeons would demonstrate bias toward early surgical intervention versus nonsurgeons. In addition, it was hypothesized that youth sports medicine professionals who were parents of a child with a previous major sports injury or concussion would be less likely to allow their child to play American tackle football or return to football after a concussion. Study Design: Cross-sectional study. Methods: An online survey was provided to the active members of the Pediatric Research in Sports Medicine Society. We used both professional background information and responses to questions related to personal experiences with youth sports injuries to determine potential factors associated with underlying biases. Survey responses among subgroups were compared using the Fisher exact test. The Pearson correlation coefficient was used to evaluate years in practice versus opioid use. Results: Of the survey participants, 62.5% were pediatric surgeons, and 37.5% represented different nonsurgical youth sports medicine professions. Surgeons were less likely than nonsurgeons to agree to allow their child to return to football after sustaining a concussion and completing a concussion protocol (48% vs 76%, P = .013). Surgeons were more likely than nonsurgeons to agree to both elective shoulder stabilization after a first-time dislocation and elective drilling of a stable knee osteochondritis dissecans (OCD) before nonoperative treatment (41% vs 10%, P = .003 and 52% vs 23%, P = .013, respectively). Those who reported having a child with a concussion history were more likely to support him or her returning to football after a concussion (65% vs 33%, P = .026). Conclusion: Surgeons were more likely to favor elective shoulder-stabilization surgery after a first-time dislocation and drilling of a stable knee OCD instead of nonoperative management. Personal experience of having a child who sustained a major sports injury or concussion did not demonstrate a bias against participation in football or return to football after a concussion.

Glycerol-3-phosphate acyltransferase (GPAT)1 is a mitochondrial outer membrane protein that catalyzes the first step of de novo glycerolipid biosynthesis. Hepatic expression of GPAT1 is linked to liver fat accumulation and the severity of nonalcoholic fatty liver diseases. Here we present the cryo-EM structures of human GPAT1 in substrate analog-bound and product-bound states. The structures reveal an N-terminal acyltransferase domain that harbors important catalytic motifs and a tightly associated C-terminal domain that is critical for proper protein folding. Unexpectedly, GPAT1 has no transmembrane regions as previously proposed but instead associates with the membrane via an amphipathic surface patch and an N-terminal loop–helix region that contains a mitochondrial-targeting signal. Combined structural, computational and functional studies uncover a hydrophobic pathway within GPAT1 for lipid trafficking. The results presented herein lay a framework for rational inhibitor development for GPAT1. GPAT1 is a mitochondrial outer membrane protein that catalyzes the first step of glycerolipid biosynthesis. Cryo-EM structures and functional studies of human GPAT1 uncover the molecular architecture and mechanism of this important acyltransferase.

The aim of this study was to determine if learned helplessness, self-efficacy, and cognitive distortions would predict depression in a sample of 80 individuals with multiple sclerosis (MS) and 80 individuals with a spinal cord injury (SCI). As MS and SCI usually present with disparate disease courses and etiologies, a secondary objective was to determine if individuals with MS would exhibit greater levels of helplessness, cognitive distortions, and depression and lower levels of self-efficacy than those with SCI. Results indicated that helplessness and self-efficacy significantly predicted depression for both the MS and SCI groups after controlling for confounding variables. Cognitive distortions had no independent effect, indicating that cognitive distortions may have caused feelings of helplessness and low self-efficacy and, in this way, had indirect effects on depression. The MS group exhibited significantly greater levels of depression and helplessness and significantly lower levels of self-efficacy than the SCI group. It was hypothesized that it may have been the combination of an unpredictable course of disease activity and the possibility of being affected by MS in many different ways that produced greater feelings of depression, helplessness, and low self-efficacy in the MS group.

Supernova (SN) 2014C is a rare transitional event that exploded as a hydrogen-poor, helium-rich Type Ib SN and subsequently interacted with a hydrogen-rich circumstellar medium (CSM) a few months post-explosion. This unique interacting object provides an opportunity to probe the mass-loss history of a stripped-envelope SN progenitor. Using the James Webb Space Telescope (JWST), we observed SN 2014C with the Mid-Infrared Instrument Medium Resolution Spectrometer at 3477 days post-explosion (rest frame), and the Near-Infrared Spectrograph Integral Field Unit at 3568 days post-explosion, covering 1.7 to 25 \\(\\)m. The bolometric luminosity indicates that the SN is still interacting with the same CSM that was observed with the Spitzer Space Telescope 40--1920 days post-explosion. JWST spectra and near-contemporaneous optical and near-infrared spectra show strong [Ne II] 12.831 \\(\\)m, He 1.083 \\(\\)m, H\\(\\), and forbidden oxygen ([O I]$\\lambda$ $\\lambda\\(6300, 6364, [O II] \\)\\lambda$ $\\lambda\\(7319, 7330, and [O III] \\)\\lambda$ $\\lambda\\(4959, 5007) emission lines with asymmetric profiles, suggesting a highly asymmetric CSM. The mid-IR continuum can be explained by ~\\)0.036 \\ M_\\odot\\( of carbonaceous dust at ~300 K and ~0.043 \\)M_\\odot$of silicate dust at ~200 K. The observed dust mass has increased tenfold since the last Spitzer observation 4 yr ago, with evidence suggesting that new grains have condensed in the cold dense shell between the forward and reverse shocks. This dust mass places SN 2014C among the dustiest SNe in the mid-IR and supports the emerging observational trend that SN explosions produce enough dust to explain the observed dust mass at high redshifts.