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The Snapshot: Climate issue of Southern Cultures includes photography and reflections on climate impacts across the southern states by Jenny Adler, Austin Anthony, Kate Auger, Arden Barnes, Monica Patrice Barra, Robin Boggs, Jared Bramblett, Lily Brooks, Hannah Brown, Becca Burton, Matthew Busch, Gordon Campbell, Natalie Chanin, Vanessa Charlot, Walter Coker, Justin Cook, Cameron Davidson, Marquetta Dickens, Brandon Dill, Benjamin Dimmitt, Rory Doyle, Ryan Emanuel, Cameron Evans, J Henry Fair, Megan Faust, Annie Flanagan, Kathleen Flynn, Jerod Foster, John Gaulden, Hermina Glass-Hill, Allison Grant, Jerry Dickson Greer, Joshua Dudley Greer, Anna Hamilton, Virginia Hanusik, John Lusk Hathaway, Chuck Hemard, Tom Kimmerer, Virginie Kippelen, Jeremy M. Lange, Nate Larson, Mark Long, Jordan Lovejoy, Megan May, Roger May, Lisette Morales McCabe, Rob McDonald, Andrew Moore, Stephen B. Morton, Anna Gage Norton, Jocelyn Painter, Elena Peterman, Daniel Pullen, Tom Rankin, Robert Rausch, Jeff Rich, Beth Roach, Derek Slagle, Michael O. Snyder, Michael K. Steinberg, Bryan Thomas, Jacqui Thurlow-Lippisch, Simon Tye, Turcois Vazquez, Jordan Vonderhaar, Jason Matthew Walker, Will Warasila, Carlton Ward Jr., Brooke White, William Widmer, and Devin Wright.

Jointed plain concrete pavements use dowel bars to transfer load across transverse joints. The job of the designer is to optimize the number, size, and location of the dowels in a given pavement. This research used data from two different construction locations. The first project evaluated the performance of standard 1.5 inch round and elliptical shaped dowel bars at different spacing intervals using full dowel baskets. The performance potential of standard 1.5 inch round and elliptical dowels placed in the wheel paths only was also evaluated on the same project. The second project compared corrosion resistant dowel bar (stainless steel and glass fiber reinforced polymer (GFRP) dowel bars) performance to round 1.5 inch epoxy-coated steel dowel bars. The stainless steel and GFRP bars are for possible use in environments where steel corrosion may be an issue. Performance data was measured on both projects in terms of deflections, using falling weight deflectometer (FWD) data collected biannually. Joint faulting data was collected over the five-year test period for both projects. Roughness data was collected for only the elliptical dowel bar project over the five-year test period. Resilient modulus values were found by triaxial testing of the pavement subgrade samples. Performance criteria graphed verses resilient modulus allowed for the comparison of different dowels as the subgrade resilient modulus changed. The elliptical dowel bar study indicated medium elliptical dowel bars at 12 inch or 15 inch spacing perform equally to the standard 1.5 inch round dowel bars at 12 inch spacing. The elliptical study also indicated the potential use of medium elliptical dowel bars in wheel paths only. The corrosion resistance study indicated stainless steel dowels spaced at eight inch intervals were the only dowels to outperform the 12 inch spaced round 1.5 inch epoxy-coated bars.

While immunologic correlates of COVID-19 have been widely reported, their associations with post-acute sequelae of COVID-19 (PASC) remain less clear. Due to the wide array of PASC presentations, understanding if specific disease features associate with discrete immune processes and therapeutic opportunities is important. Here we profile patients in the recovery phase of COVID-19 via proteomics screening and machine learning to find signatures of ongoing antiviral B cell development, immune-mediated fibrosis, and markers of cell death in PASC patients but not in controls with uncomplicated recovery. Plasma and immune cell profiling further allow the stratification of PASC into inflammatory and non-inflammatory types. Inflammatory PASC, identifiable through a refined set of 12 blood markers, displays evidence of ongoing neutrophil activity, B cell memory alterations, and building autoreactivity more than a year post COVID-19. Our work thus helps refine PASC categorization to aid in both therapeutic targeting and epidemiological investigation of PASC. Post-acute sequelae of COVID-19 (PASC) has heterogenous presentation and complex etiology. Here the authors profile peripheral blood of patients with PASC and analyze by machine-learning to identify immune and serology features that allow the stratification of PASC into inflammatory and non-inflammatory types for better diagnosis and therapy-planning.

Engineering domains in ferroelectric thin films is crucial for realizing technological applications including non-volatile data storage and solar energy harvesting. Size and shape of domains strongly depend on the electrical and mechanical boundary conditions. Here we report the origin of nonswitchable polarization under external bias that leads to energetically unfavourable head-to-head domain walls in as-grown epitaxial PbZr 0.2 Ti 0.8 O 3 thin films. By mapping electrostatic potentials and electric fields using off-axis electron holography and electron-beam-induced current with in situ electrical biasing in a transmission electron microscope, we show that electronic band bending across film/substrate interfaces locks local polarization direction and further produces unidirectional biasing fields, inducing nonswitchable domains near the interface. Presence of oxygen vacancies near the film surface, as revealed by electron-energy loss spectroscopy, stabilizes the charged domain walls. The formation of charged domain walls and nonswitchable domains reported in this study can be an origin for imprint and retention loss in ferroelectric thin films. Domain walls play an important role in the switching of ferroelectrics. Here, mapping out electric fields within ferroelectric thin films, the authors uncover electronic band bending as the origin of head-to-head domain walls that are difficult to switch and may hamper ferroelectric device performance.

There has been an increased focus on the neurological sequelae of repetitive mild traumatic brain injury (TBI), particularly neurodegenerative syndromes, such as chronic traumatic encephalopathy (CTE); however, no animal model exists that captures the behavioral spectrum of this phenomenon. We sought to develop an animal model of CTE. Our novel model is a modification and fusion of two of the most popular models of TBI and allows for controlled closed-head impacts to unanesthetized mice. Two-hundred and eighty 12-week-old mice were divided into control, single mild TBI (mTBI), and repetitive mTBI groups. Repetitive mTBI mice received six concussive impacts daily for 7 days. Behavior was assessed at various time points. Neurological Severity Score (NSS) was computed and vestibulomotor function tested with the wire grip test (WGT). Cognitive function was assessed with the Morris water maze (MWM), anxiety/risk-taking behavior with the elevated plus maze, and depression-like behavior with the forced swim/tail suspension tests. Sleep electroencephalogram/electromyography studies were performed at 1 month. NSS was elevated, compared to controls, in both TBI groups and improved over time. Repetitive mTBI mice demonstrated transient vestibulomotor deficits on WGT. Repetitive mTBI mice also demonstrated deficits in MWM testing. Both mTBI groups demonstrated increased anxiety at 2 weeks, but repetitive mTBI mice developed increased risk-taking behaviors at 1 month that persist at 6 months. Repetitive mTBI mice exhibit depression-like behavior at 1 month. Both groups demonstrate sleep disturbances. We describe the neurological sequelae of repetitive mTBI in a novel mouse model, which resemble several of the neuropsychiatric behaviors observed clinically in patients sustaining repetitive mild head injury.

The Wnt signaling pathways play pivotal roles in carcinogenesis. Modulation of the cell-surface abundance of Wnt receptors is emerging as an important mechanism for regulating sensitivity to Wnt ligands. Endocytosis and degradation of the Wnt receptors Frizzled (Fzd) and lipoprotein-related protein 6 (LRP6) are regulated by the E3 ubiquitin ligases zinc and ring finger 3 (ZNRF3) and ring finger protein 43 (RNF43), which are disrupted in cancer. In a genome-wide small interfering RNA screen, we identified the deubiquitylase ubiquitin-specific protease 6 (USP6) as a potent activator of Wnt signaling. USP6 enhances Wnt signaling by deubiquitylating Fzds, thereby increasing their cell-surface abundance. Chromosomal translocations in nodular fasciitis result in USP6 overexpression, leading to transcriptional activation of the Wnt/β-catenin pathway. Inhibition of Wnt signaling using Dickkopf-1 (DKK1) or a Porcupine (PORCN) inhibitor significantly decreased the growth of USP6-driven xenograft tumors, indicating that Wnt signaling is a key target of USP6 during tumorigenesis. Our study defines an additional route to ectopic Wnt pathway activation in human disease, and identifies a potential approach to modulate Wnt signaling for therapeutic benefit.

The genetic basis of autoantibody production is largely unknown outside of associations located in the major histocompatibility complex (MHC) human leukocyte antigen (HLA) region. The aim of this study is the discovery of new genetic associations with autoantibody positivity using genome-wide association scan single nucleotide polymorphism (SNP) data in type 1 diabetes (T1D) patients with autoantibody measurements. We measured two anti-islet autoantibodies, glutamate decarboxylase (GADA, n = 2,506), insulinoma-associated antigen 2 (IA-2A, n = 2,498), antibodies to the autoimmune thyroid (Graves') disease (AITD) autoantigen thyroid peroxidase (TPOA, n = 8,300), and antibodies against gastric parietal cells (PCA, n = 4,328) that are associated with autoimmune gastritis. Two loci passed a stringent genome-wide significance level (p<10(-10)): 1q23/FCRL3 with IA-2A and 9q34/ABO with PCA. Eleven of 52 non-MHC T1D loci showed evidence of association with at least one autoantibody at a false discovery rate of 16%: 16p11/IL27-IA-2A, 2q24/IFIH1-IA-2A and PCA, 2q32/STAT4-TPOA, 10p15/IL2RA-GADA, 6q15/BACH2-TPOA, 21q22/UBASH3A-TPOA, 1p13/PTPN22-TPOA, 2q33/CTLA4-TPOA, 4q27/IL2/TPOA, 15q14/RASGRP1/TPOA, and 12q24/SH2B3-GADA and TPOA. Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A).

Fall risk assessment needs contemporary approaches based on habitual data. Currently, inertial measurement unit (IMU)-based wearables are used to inform free-living spatio-temporal gait characteristics to inform mobility assessment. Typically, a fluctuation of those characteristics will infer an increased fall risk. However, current approaches with IMUs alone remain limited, as there are no contextual data to comprehensively determine if underlying mechanistic (intrinsic) or environmental (extrinsic) factors impact mobility and, therefore, fall risk. Here, a case study is used to explore and discuss how contemporary video-based wearables could be used to supplement arising mobility-based IMU gait data to better inform habitual fall risk assessment. A single stroke survivor was recruited, and he conducted a series of mobility tasks in a lab and beyond while wearing video-based glasses and a single IMU. The latter generated topical gait characteristics that were discussed according to current research practices. Although current IMU-based approaches are beginning to provide habitual data, they remain limited. Given the plethora of extrinsic factors that may influence mobility-based gait, there is a need to corroborate IMUs with video data to comprehensively inform fall risk assessment. Use of artificial intelligence (AI)-based computer vision approaches could drastically aid the processing of video data in a timely and ethical manner. Many off-the-shelf AI tools exist to aid this current need and provide a means to automate contextual analysis to better inform mobility from IMU gait data for an individualized and contemporary approach to habitual fall risk assessment.

Extreme weather events perturb ecosystems and increasingly threaten biodiversity 1 . Ecologists emphasize the need to forecast and mitigate the impacts of these events, which requires knowledge of how risk is distributed among species and environments. However, the scale and unpredictability of extreme events complicate risk assessment 1 – 4 —especially for large animals (megafauna), which are ecologically important and disproportionately threatened but are wide-ranging and difficult to monitor 5 . Traits such as body size, dispersal ability and habitat affiliation are hypothesized to determine the vulnerability of animals to natural hazards 1 , 6 , 7 . Yet it has rarely been possible to test these hypotheses or, more generally, to link the short-term and long-term ecological effects of weather-related disturbance 8 , 9 . Here we show how large herbivores and carnivores in Mozambique responded to Intense Tropical Cyclone Idai, the deadliest storm on record in Africa, across scales ranging from individual decisions in the hours after landfall to changes in community composition nearly 2 years later. Animals responded behaviourally to rising floodwaters by moving upslope and shifting their diets. Body size and habitat association independently predicted population-level impacts: five of the smallest and most lowland-affiliated herbivore species declined by an average of 28% in the 20 months after landfall, while four of the largest and most upland-affiliated species increased by an average of 26%. We attribute the sensitivity of small-bodied species to their limited mobility and physiological constraints, which restricted their ability to avoid the flood and endure subsequent reductions in the quantity and quality of food. Our results identify general traits that govern animal responses to severe weather, which may help to inform wildlife conservation in a volatile climate. A study that tracked mammal populations before, during and after a severe storm in Mozambique’s Gorongosa National Park finds that behavioural responses and survival are linked to body size, with increased mortality of small species owing to limited mobility and changes in food availability.