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Clinical presentation, outcomes, and duration of COVID-19 has ranged dramatically. While some individuals recover quickly, others suffer from persistent symptoms, collectively known as long COVID, or post-acute sequelae of SARS-CoV-2 (PASC). Most PASC research has focused on hospitalized COVID-19 patients with moderate to severe disease. We used data from a diverse population-based cohort of Arizonans to estimate prevalence of PASC, defined as experiencing at least one symptom 30 days or longer, and prevalence of individual symptoms. There were 303 non-hospitalized individuals with a positive lab-confirmed COVID-19 test who were followed for a median of 61 days (range 30-250). COVID-19 positive participants were mostly female (70%), non-Hispanic white (68%), and on average 44 years old. Prevalence of PASC at 30 days post-infection was 68.7% (95% confidence interval: 63.4, 73.9). The most common symptoms were fatigue (37.5%), shortness-of-breath (37.5%), brain fog (30.8%), and stress/anxiety (30.8%). The median number of symptoms was 3 (range 1-20). Amongst 157 participants with longer follow-up (≥60 days), PASC prevalence was 77.1%.

In the Northern Rockies of the United States, predators like wolves (Canis lupus) and mountain lions (Puma concolor) have been implicated in fluctuations or declines in populations of game species like elk (Cervus canadensis) and mule deer (Odocoileus hemionus). In particular, local distributions of these predators may affect ungulate behavior, use of space, and dynamics. Our goal was to develop generalizable predictions of habitat selection by wolves and mountain lions across western Montana. We hypothesized both predator species would select habitat that maximized their chances of encountering and killing ungulates and that minimized their chances of encountering humans. We assessed habitat selection by these predators during summer using within-home range (3rd order) resource selection functions (RSFs) in multiple study areas throughout western Montana, and tested how generalizable RSF predictions were by applying them to out-of-sample telemetry data from separate study areas. Selection for vegetation cover-types varied substantially among wolves in different study areas. Nonetheless, our predictions of 3rd order selection by wolves were highly generalizable across different study areas. Wolves consistently selected simple topography where ungulate prey may be more susceptible to their cursorial hunting mode. Topographic features may serve as better proxies of predation risk by wolves than vegetation cover-types. Predictions of mountain lion distribution were less generalizable. Use of rugged terrain by mountain lions varied across ecosystem-types, likely because mountain lions targeted the habitats of different prey species in each study area. Our findings suggest that features that facilitate the hunting mode of a predator (i.e. simple topography for cursorial predators and hiding cover for stalking predators) may be more generalizable predictors of their habitat selection than features associated with local prey densities.

As the need for new modalities of energy storage becomes increasingly important, all-solid-state secondary ion batteries seem poised to address a portion of tomorrow’s energy needs. The success of such batteries is contingent on the solid-state electrolyte (SSE) meeting a set of material demands, including high bulk and interfacial ionic conductivity, processability with electrodes, electrode interfacial stability, thermal stability, etc. The demanding criteria for an ideal SSE has translated into decades of research devoted to discovering new electrolytes and modifying their structure/processing to improve their properties. While much research has focused on the electrolyte properties of polycrystalline ceramics, non-crystalline materials (glasses, amorphous solids, and partially crystallized materials) have demonstrated unique advantages in processability, stability, tunability, etc. These non-crystalline electrolytes are also fundamentally interesting for their potential contributions toward understanding ionic conduction in the solid state. In this review, we first review a decade of advances in two distinct families of non-crystalline lithium-ion electrolytes: lithium thiophosphate and lithium phosphate oxynitride. In doing so, we demonstrate two pathways for non-crystalline electrolytes to address the barriers toward development of all-solid-state batteries, viz., interfacial stability and conduction. Finally, we conclude with some discussion of the development of fundamental models of ionic conduction in the non-crystalline state, including the ongoing debate between strong and weak electrolyte theories. Collectively, these discussions make a promising case for the role of non-crystalline electrolytes in the next generation of energy storage technology.

Background: Dietary protein serves a pivotal role in providing the body with essential amino acids, which are required for the maintenance of body proteins, and the assimilation of structural and functional components required for basic survival. Understanding how dietary protein sources potentially vary for different population subgroups will allow for future nutrition interventions to be more targeted for specific needs.Objective: The purpose of this analysis was to identify the top ten food category sources of dietary protein by age and race and ethnicity in a nationally representative sample.Methods: Cross-sectional data on adults (18+ years) from the National Health and Nutrition Examination Survey (NHANES) 2011–2016 with one 24-h dietary recall were analyzed (n = 15,697). Population proportions were calculated based on protein intake (g/day) for What We Eat In America food categories.Results: The analytic sample (n = 15,697) was 15.0% Hispanic (95% CI [12.1, 17.9], 65.0% non-Hispanic White (95% CI [60.8, 69.3]), 11.5% non-Hispanic Black (95% CI [9.1, 13.9]), 5.4% non-Hispanic Asian (95% CI [4.3, 6.6]), and 3.1% other (95% CI [2.5, 3.6]). In all racial and ethnic groups, as well as age categories, chicken (whole pieces) was the top-ranked source of dietary protein. In addition to chicken (whole pieces), beef (excludes ground), eggs and omelets, and meat mixed dishes food categories ranked in the top ten sources of protein for every race/ethnicity. Only two solely plant-based proteins appeared in the top ten sources: beans, peas and legumes for Hispanics, and nuts and seeds for Other. For all age categories, beef (excludes ground) was among the top five sources and egg/omelets appear in the top ten sources.Conclusion: The top ten sources of protein accounted for over 40% of dietary protein irrespective of race/ethnicity or age category, having major implications for the sustainability of our nation's food supply. Public health strategies that encourage diversity in protein sources in food preparation and incorporate legumes and nuts along with poultry have the potential to shift the overall population protein intake distribution toward improving overall diet quality.

Abstract Environmental DNA (eDNA) is the DNA suspended in the environment (e.g., water column), which includes cells, gametes, and other material derived from but not limited to shedding of tissue, scales, mucus, and fecal matter. Amplifying and sequencing marker genes (i.e., metabarcoding) from eDNA can reveal the wide range of taxa present in an ecosystem through analysis of a single water sample. Metabarcoding of eDNA provides higher resolution data than visual surveys, aiding in assessments of ecosystem health. This study conducted eDNA metabarcoding of two molecular markers (cytochrome c oxidase I (COI) and 18S ribosomal RNA (rRNA) genes) to survey eukaryotic diversity across multiple trophic levels in surface water samples collected at three sites along the coral reef tract within the Florida Keys National Marine Sanctuary (FKNMS) during four research cruises in 2015. The 18S rRNA gene sequences recovered 785 genera while the COI gene sequences recovered 115 genera, with only 33 genera shared between the two datasets, emphasizing the complementarity of these marker genes. Community composition for both genetic markers clustered by month of sample collection, suggesting that temporal variation has a larger effect on biodiversity than spatial variability in the FKNMS surface waters. Sequences from both marker genes were dominated by copepods, but each marker recovered distinct phytoplankton groups, with 18S rRNA gene sequences dominated by dinoflagellates and COI sequences dominated by coccolithophores. Although eDNA samples were collected from surface waters, many benthic species such as sponges, crustaceans, and corals were identified. These results show the utility of eDNA metabarcoding for cataloging biodiversity to establish an ecosystem baseline against which future samples can be compared in order to monitor community changes.

Notch pathway haploinsufficiency can cause severe developmental syndromes with highly variable penetrance. Currently, we have a limited mechanistic understanding of phenotype variability due to gene dosage. Here, we unexpectedly found that inserting an enhancer containing pioneer transcription factor sites coupled to Notch dimer sites can induce a subset of Notch haploinsufficiency phenotypes in Drosophila with wild type Notch gene dose. Using Drosophila genetics, we show that this enhancer induces Notch phenotypes in a Cdk8-dependent, transcription-independent manner. We further combined mathematical modeling with quantitative trait and expression analysis to build a model that describes how changes in Notch signal production versus degradation differentially impact cellular outcomes that require long versus short signal duration. Altogether, these findings support a ‘bind and discard’ mechanism in which enhancers with specific binding sites promote rapid Cdk8-dependent Notch turnover, and thereby reduce Notch-dependent transcription at other loci and sensitize tissues to gene dose based upon signal duration.

Overexpression of oncoproteins is a major cause of treatment failure using current chemotherapeutic drugs. Drug‐induced degradation of oncoproteins is feasible and can improve clinical outcomes in diverse types of cancers. Mortalin‐2 (mot‐2) is a dominant oncoprotein in several tumors, including colorectal cancer (CRC). In addition to inactivating the p53 tumor suppressor protein, mot‐2 enhances tumor cell invasion and migration. Thus, mot‐2 is considered a potential therapeutic target in several cancer types. The current study investigated the biological role of a ubiquitin‐like protein called UBXN2A in the regulation of mot‐2 turnover. An orthogonal ubiquitin transfer technology followed by immunoprecipitation, in vitro ubiquitination, and Magnetic Beads TUBE2 pull‐down experiments revealed that UBXN2A promotes carboxyl terminus of the HSP70‐interacting protein (CHIP)‐dependent ubiquitination of mot‐2. We subsequently showed that UBXN2A increases proteasomal degradation of mot‐2. A subcellular compartmentalization experiment revealed that induced UBXN2A decreases the level of mot‐2 and its chaperone partner, HSP60. Pharmacological upregulation of UBXN2A using a small molecule, veratridine (VTD), decreases the level of mot‐2 in cancer cells. Consistent with the in vitro results, UBXN2A+/− mice exhibited selective elevation of mot‐2 in colon tissues. An in vitro Anti‐K48 TUBE isolation approach showed that recombinant UBXN2A enhances proteasomal degradation of mot‐2 in mouse colon tissues. Finally, we observed enhanced association of CHIP with the UBXN2A‐mot‐2 complex in tumors in an azoxymethane/dextran sulfate sodium‐induced mouse CRC model. The existence of a multiprotein complex containing UBXN2A, CHIP, and mot‐2 suggests a synergistic tumor suppressor activity of UBXN2A and CHIP in mot‐2‐enriched tumors. This finding validates the UBXN2A‐CHIP axis as a novel and potential therapeutic target in CRC.

Polypharmacy of psychotropic medications predisposes older adults to adverse drug events (ADEs). One contributing factor is inhibition of metabolic pathways between substrates (competitive inhibition) or between substrates and inhibitors of the same cytochrome P450 (CYP450) isoforms. The purpose of this case report is to demonstrate observed sedation and difficulty concentrating from augmentation therapy for resistant major depressive disorder (MDD) and to highlight the value of clinical tools to identify opportunities for treatment optimization to reduce ADEs. The pharmacist identified significant medication burden and competitive inhibition of drug metabolism in the CYP450 system during a telehealth medication therapy management consultation with a 69-year-old male. The pharmacist recommended clinical monitoring and communicated concerns about medication-induced sedation, difficulty concentrating, and other medication-related problems (MRP) to providers. Several recommendations were implemented which helped improved patient’s outcomes. Individualizing MDD pharmacotherapy based on pharmacokinetic and pharmacodynamic drug interactions and geriatric dosage considerations may lead to better outcomes and tolerability among older adults.

Sediment management is a fundamental part of reservoir operation, but it is often complicated by metal(loid) enrichment in sediments. Knowledge concerning the sources of potential contaminants is therefore of important significance. To address this issue, the concentrations and the mobile fractions of metal(loid)s were determined in the sediments and the respective catchment areas of six reservoirs. The results indicate that reservoirs generally have a high potential for contaminated sediment accumulation due to preferential deposition of fine particles. The median values of the element-specific enrichment factor (EF) demonstrates slight enrichments of arsenic (EF: 3.4), chromium (EF: 2.8), and vanadium (EF: 2.9) for reservoir sediments. The enrichments of cadmium (EF: 8.2), manganese (EF: 3.9), nickel (EF: 4.8), and zinc (EF: 5.0) are significantly higher. This is enabled by a diffuse element release from the soils into the impounded streams, which is particularly favored by soil acidity. Leaching from the catchment soils partially enriches elements in stream sediments before their fine-grained portions in particular are deposited as reservoir sediment. We assume that this effect is of high relevance especially for reservoirs impounding small streams with forested catchments and weakly acid buffering parent material of soil formation.

Soils contain an increasing number of different pollutants, which are often released into the environment by human activity. Among the “new” potential pollutants are plastics and microplastics. “Recognized” pollutants such as heavy metals, of geogenic and anthropogenic origin, now meet purely anthropogenic contaminants such as plastic particles. Those can meet especially in floodplain landscapes and floodplain soils, because of their function as a temporary sink for sediments, nutrients, and pollutants. Based on a geospatial sampling approach, we analyzed the soil properties and heavy metal contents (ICP-MS) in soil material and macroplastic particles, and calculated total plastic concentrations (Ptot) from preliminary studies. Those data were used to investigate spatial connections between both groups of pollutants. Our results from the example of the Lahn river catchment show a low-to-moderate contamination of the floodplain soils with heavy metals and a wide distribution of plastic contents up to a depth of two meters. Furthermore, we were able to document heavy metal contents in macroplastic particles. Spatial and statistical correlations between both pollutants were found. Those correlations are mainly expressed by a comparable variability in concentrations across the catchment and in a common accumulation in topsoil and upper soil or sediment layers (0–50 cm). The results indicate comparable deposition conditions of both pollutants in the floodplain system.

The crystal structure of complexes of 3,4,5-trimethyl-1H-pyrazole with CuCl2·2H2O and Cu(NO3)2·2.5H2O are presented, namely di-μ-chlorido-bis[chloridobis(3,4,5-trimethyl-1H-pyrazole-κN2)copper(II)], [Cu2Cl4(C6H10N2)4] (1) and aquatetrakis(3,4,5-trimethyl-1H-pyrazole-κN2)copper(II) dinitrate, [Cu(C6H10N2)4(H2O)](NO3)2 (2), and compared to the previously determined structures for 3-methyl-1H-pyrazole and 3,5-dimethyl-1H-pyrazole. CuCl2 forms a 2:1 ligand-to-metal chloride-bridged complex with 3,4,5-trimethyl-1H-pyrazole, with a square-pyramidal coordination geometry about each copper(II) center. Similarly to the previously obtained 3,5-dimethyl-1H-pyrazole complex with CuCl2, the pyrazole ligands are cis to each other, with two chloride ions bridging the two copper(II) centers, and a terminal chloride ion occupying the axial position. Cu(NO3)2 forms a 4:1 ligand-to-metal complex with 3,4,5-trimethyl-1H-pyrazole that is also arranged in a square-pyramidal geometry about CuII. The newly obtained copper(II) complex has the same coordination geometry as the 3,5-dimethyl-1H-pyrazole complex, including an axial water molecule, two nitrate ions hydrogen-bonded to the water molecule, and four pyrazole ligands in the equatorial plane, suggesting that similar steric forces are at play in the formation of these complexes.

The degree of relaxation in any glass sample is a governing property in every property of the glass. It plays an important role in every major glass product commercially available, but has required individual groups to develop their own relaxation codes. RelaxPy is a Python-based script designed to be used in a Python interpreter or Linux terminal. Given an input temperature path and set of material properties including the nonequilibrium viscosity parameters, RelaxPy returns the evolution of the composite fictive temperature, viscosity, and relaxation time. Optionally, the software can also return the individual values of the fictive temperature components using a Prony series fit to approximate the stretched exponential relaxation form. RelaxPy aims to provide a flexible, open-source framework for glass relaxation modeling where new advances in glass physics can be easily incorporated and shared with the community. Keywords: Glass, Thermodynamics, Viscosity, Relaxation, Fictive temperature, Kinetics

Facioscapulohumeral muscular dystrophy is a severe myopathy that is caused by abnormal activation of DUX4, and for which a suitable mouse model does not exist. Here, the authors generate a novel mouse model with titratable expression of DUX4, and show that it recapitulates several features of the human pathology.

Monitoring aquatic species by identification of environmental DNA (eDNA) is becoming more common. To obtain quantitative eDNA datasets for individual species, organism-specific quantitative PCR (qPCR) assays are required. Here, we present detailed methodology of qPCR assay design and testing, including in silico, in vitro, and in vivo testing, and comment on the challenges associated with assay design and performance. We use the presented methodology to design assays for three important marine organisms common in the California Current Ecosystem (CCE): humpback whale (Megaptera novaeangliae), shortbelly rockfish (Sebastes jordani), and common murre (Uria aalge). All three assays have excellent sensitivity and high efficiencies ranging from 92% to 99%. However, specificities of the assays varied from species-specific in the case of common murre, genus-specific for the shortbelly rockfish assay, and broadly whale-specific for the humpback whale assay, which cross-amplified with other two other whale species, including one in a different family. All assays detected their associated targets in complex environmental water samples.

Energy landscapes are a powerful tool for describing the kinetics of complex systems at the atomic scale. However, because of the large disparity of time scales of kinetic processes, it can be difficult to calculate the evolution of properties over long (e.g., experimental) time scales. KineticPy is a Python-based program designed to calculate the evolution of occupational probabilities of every basin in an energy landscape (or enthalpy landscape), taking advantage of the disparate time scales of the system to accelerate the calculations utilizing the framework of broken ergodicity. Given the relevant parameters of the energy landscape (i.e., the set of inherent structures, transition points, and corresponding property values) and a desired temperature path, KineticPy calculates the kinetics of the landscape on any arbitrary time scale. KineticPy offers a unified platform for exploring energy landscapes and calculating the evolution of property values for any system of interest. KineticPy is open source and structured in a modular fashion to facilitate future extensions to the code.

Environmental DNA (eDNA) metabarcoding is a new approach for assessing marine biodiversity that may overcome challenges of traditional monitoring and complement both existing surveys and biodiversity assessments. There are limited eDNA studies that evaluate vertebrate biodiversity in the marine environment or compare patterns of biodiversity with traditional methods. This study uses eDNA metabarcoding of the mitochondrial 12S rRNA genes present in seawater samples to characterize vertebrate biodiversity and distribution within National Marine Sanctuaries located in the California Current upwelling ecosystem. The epipelagic community in the study region has been monitored using traditional (mid-water trawl and marine mammal) survey methods since 1983. During 2016 and 2017, we concurrently sampled the epipelagic community using traditional survey methods and water for eDNA analysis to assess agreement among the methods. We collected replicate eDNA samples from 25 stations at depths of 10, 40, and 80 m, resulting in 131 small volume (1 L) environmental water samples to examine eDNA sequences. Across the eDNA and traditional survey methods, 80 taxa were identified. Taxa identified by eDNA partially overlapped with taxa through trawl and marine mammal surveys, but more taxa were identified by eDNA. Diversity and distribution patterns of marine vertebrates inferred from eDNA sequences reflected known spatial distribution patterns in species occurrence and community structure (e.g., cross-shelf and alongshore patterns). During both years, we identified fishery taxa Sebastes (rockfish), Merluccius (hake), Citharichthys (sanddab), and Engraulis (anchovy) across the majority of the stations using eDNA metabarcoding. The marine vertebrate assemblage identified by eDNA in 2016 was statistically different from the 2017 assemblage and more marine mammals were identified in 2017 than in 2016. Differences in assemblages identified by eDNA were coincident with different oceanographic conditions (e.g., upwelling and stratification). In 2016, weak upwelling and warmer than average conditions were measured, and vertebrate assemblages were not different among ecological regions [Point Reyes, Pescadero, and Monterey Bay]. While in 2017, average upwelling conditions returned, vertebrate assemblages differed at each region. This study illustrates that eDNA provides a new baseline for vertebrate assessments that can both augment traditional biomonitoring surveys and aid our understanding of changes in biodiversity.

Crimean-Congo hemorrhagic fever (CCHF) is the most medically important tick-borne viral disease of humans and tuberculosis is the leading cause of death worldwide by a bacterial pathogen. These two diseases overlap geographically, however, concurrent infection of CCHF virus (CCHFV) with mycobacterial infection has not been assessed nor has the ability of virus to persist and cause long-term sequela in a primate model. In this study, we compared the disease progression of two diverse strains of CCHFV in the recently described cynomolgus macaque model. All animals demonstrated signs of clinical illness, viremia, significant changes in clinical chemistry and hematology values, and serum cytokine profiles consistent with CCHF in humans. The European and Asian CCHFV strains caused very similar disease profiles in monkeys, which demonstrates that medical countermeasures can be evaluated in this animal model against multiple CCHFV strains. We identified evidence of CCHFV persistence in the testes of three male monkeys that survived infection. Furthermore, the histopathology unexpectedly revealed that six additional animals had evidence of a latent mycobacterial infection with granulomatous lesions. Interestingly, CCHFV persisted within the granulomas of two animals. This study is the first to demonstrate the persistence of CCHFV in the testes and within the granulomas of non-human primates with concurrent latent tuberculosis. Our results have important public health implications in overlapping endemic regions for these emerging pathogens.

Lithium borate glasses exhibit the “boron anomaly” and clustering of the lithium ions. Bødker et.al (Bødker, Mauro, Youngman, & Smedskjaer, 2019) predicted the Tg using statistical mechanics and topological constraint theory (TCT) over a wide range of contents (to 65 mol% Li2O). Although Bødker's model predicted the fraction of the structures present, this paper examines the linkage between intermediate-range structures and properties of the glasses. Tg was found using TCT with the structural model of Feller, Dell, and Bray (Feller, Dell, Bray, 1982). The topology of the intermediate-range structure was related to rigidity, and to lithium clustering. Keywords: Borate, Structure, Topological constraint theory, Conductivity, Tg, Modeling

The elastic response of glass is one of its most important properties for a wide range of applications in architecture, transportation, information display, and healthcare. Unfortunately, there is currently no model to predict quantitatively accurate values of elastic moduli from the underlying network topology of the glass. Here we introduce a topological model to calculate the Young's modulus of glass in terms of the free energy density of rigid constraints in the network. The model shows quantitatively accurate agreement with glasses across a variety of compositional families. More remarkably, the variation of modulus with temperature can also be predicted by accounting for the temperature dependence of the constraints, including the approach to the viscoelastic region near the glass transition. Keywords: Disordered solids, Glasses, Elasticity, Elastic moduli

In order to quantify the temporal effects on the glass transition at relativistic speeds, the Deborah number is analyzed incorporating the Maxwell relation for relaxation time. Using the time dilation coefficient proposed by Einstein for special relativity, the new observation times are calculated, and the corresponding shear modulus is used to determine the shift in the glass transition temperature. The new glass transition temperature is incorporated into the MYEGA expression to estimate the relativistic viscosity curve. B2O3 glass is used as an example to show the impact of relativistic time scales on viscosity and the glass transition. Keywords: Glass transition, Relativity, Viscosity

Loss of crop protection products when agricultural spray applications drift has economic and ecological consequences. Modification of the spray solution through tank additives and product formulation is an important drift reduction strategy that could mitigate these effects, but has been studied less than most other strategies. Therefore, an experimental field study was conducted to evaluate spray drift resulting from agricultural ground applications of an insecticide formulated as a suspension concentrate (SC) and as a wettable powder (WP), with and without two adjuvants. Droplet sizes were also measured in a wind tunnel to determine if indirect methods could be substituted for field experimentation to quantify spray drift from these technologies. Results suggest that spray drift was reduced by 37% when comparing the SC to the WP formulation. As much as 63% drift reduction was achieved by incorporating certain spray adjuvants, but this depended on the formulation/adjuvant combination. The wind tunnel data for droplet spectra showed strong agreement with field deposition trends, suggesting that droplet statistics could be used to estimate drift reduction of spray solutions. These findings can be used to develop a classification scheme for formulated products and tank additives based on their potential for reducing spray drift.

The rapid response of photosynthetic organisms to fluctuations in ambient light intensity is incompletely understood at both the molecular and membrane levels. In this review, we describe research from our group over a 10-year period aimed at identifying the photophysical mechanisms used by plants, algae and mosses to control the efficiency of light harvesting by photosystem II on the seconds-to-minutes time scale. To complement the spectroscopic data, we describe three models capable of describing the measured response at a quantitative level. The review attempts to provide an integrated view that has emerged from our work, and briefly looks forward to future experimental and modelling efforts that will refine and expand our understanding of a process that significantly influences crop yields.

A central goal of photoprotective energy dissipation processes is the regulation of singlet oxygen (1O2*) and reactive oxygen species in the photosynthetic apparatus. Despite the involvement of 1O2* in photodamage and cell signaling, few studies directly correlate 1O2* formation to nonphotochemical quenching (NPQ) or lack thereof. Here, we combine spin-trapping electron paramagnetic resonance (EPR) and time-resolved fluorescence spectroscopies to track in real time the involvement of 1O2* during photoprotection in plant thylakoid membranes. The EPR spin-trapping method for detection of 1O2* was first optimized for photosensitization in dye-based chemical systems and then used to establish methods for monitoring the temporal dynamics of 1O2* in chlorophyll-containing photosynthetic membranes. We find that the apparent 1O2* concentration in membranes changes throughout a 1 h period of continuous illumination. During an initial response to high light intensity, the concentration of 1O2* decreased in parallel with a decrease in the chlorophyll fluorescence lifetime via NPQ. Treatment of membranes with nigericin, an uncoupler of the transmembrane proton gradient, delayed the activation of NPQ and the associated quenching of 1O2* during high light. Upon saturation of NPQ, the concentration of 1O2* increased in both untreated and nigericin-treated membranes, reflecting the utility of excess energy dissipation in mitigating photooxidative stress in the short term (i.e., the initial ∼10 min of high light).

The field of cardiovascular fetal programming has emphasized the importance of the uterine environment on postnatal cardiovascular health. Studies have linked increased fetal glucocorticoid exposure, either from exogenous sources (such as dexamethasone (Dex) injections), or from maternal stress, to the development of adult cardiovascular pathologies. Although the mechanisms are not fully understood, alterations in gene expression driven by altered oxidative stress and epigenetic pathways are implicated in glucocorticoid-mediated cardiovascular programming. Antioxidants, such as the naturally occurring polyphenol epigallocatechin gallate (EGCG), or the superoxide dismutase (SOD) 4-hydroxy-TEMPO (TEMPOL), have shown promise in the prevention of cardiovascular dysfunction and programming. This study investigated maternal antioxidant administration with EGCG or TEMPOL and their ability to attenuate the fetal programming of hypertension via Dex injections in WKY rats. Results from this study indicate that, while Dex-programming increased blood pressure in male and female adult offspring, administration of EGCG or TEMPOL via maternal drinking water attenuated Dex-programmed increases in blood pressure, as well as changes in adrenal mRNA and protein levels of catecholamine biosynthetic enzymes phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), dopamine beta hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT), in a sex-specific manner. Furthermore, programmed male offspring displayed reduced antioxidant glutathione peroxidase 1 (Gpx1) expression, increased superoxide dismutase 1 (SOD1) and catalase (CAT) expression, and increased pro-oxidant NADPH oxidase activator 1 (Noxa1) expression in the adrenal glands. In addition, prenatal Dex exposure alters expression of epigenetic regulators histone deacetylase (HDAC) 1, 5, 6, 7, 11, in male and HDAC7 in female offspring. These results suggest that glucocorticoids may mediate the fetal programming of hypertension via alteration of epigenetic machinery and oxidative stress pathways.

Carbon-based electrodes combined with fast-scan cyclic voltammetry (FSCV) enable neurochemical sensing with high spatiotemporal resolution and sensitivity. While their attractive electrochemical and conductive properties have established a long history of use in the detection of neurotransmitters both in vitro and in vivo, carbon fiber microelectrodes (CFMEs) also have limitations in their fabrication, flexibility, and chronic stability. Diamond is a form of carbon with a more rigid bonding structure (sp3-hybridized) which can become conductive when boron-doped. Boron-doped diamond (BDD) is characterized by an extremely wide potential window, low background current, and good biocompatibility. Additionally, methods for processing and patterning diamond allow for high-throughput batch fabrication and customization of electrode arrays with unique architectures. While tradeoffs in sensitivity can undermine the advantages of BDD as a neurochemical sensor, there are numerous untapped opportunities to further improve performance, including anodic pretreatment, or optimization of the FSCV waveform, instrumentation, sp2/sp3 character, doping, surface characteristics, and signal processing. Here, we review the state-of-the-art in diamond electrodes for neurochemical sensing and discuss potential opportunities for future advancements of the technology. We highlight our team’s progress with the development of an all-diamond fiber ultramicroelectrode as a novel approach to advance the performance and applications of diamond-based neurochemical sensors.

The development of various biosensors has revolutionized the healthcare industry by providing rapid and reliable detection capability. Printed circuit board (PCB) technology has a well-established industry widely available around the world. In addition to electronics, this technology has been utilized to fabricate electrical parts, including electrodes for different biological and chemical sensors. High reproducibility achieved through long-lasting standard processes and low-cost resulting from an abundance of competitive manufacturing services makes this fabrication method a prime candidate for patterning electrodes and electrical parts of biosensors. The adoption of this approach in the fabrication of sensing platforms facilitates the integration of electronics and microfluidics with biosensors. In this review paper, the underlying principles and advances of printed board circuit technology are discussed. In addition, an overview of recent advancements in the development of PCB-based biosensors is provided. Finally, the challenges and outlook of PCB-based sensors are elaborated.

Climate change is projected to aggravate water quality impairment and to endanger drinking water supply. The effects of global warming on water quality must be understood better to develop targeted mitigation strategies. We conducted water and sediment analyses in the eutrophicated Antrift catchment (Hesse, Germany) in the uncommonly warm years 2018/2019 to take an empirical look into the future under climate change conditions. In our study, algae blooms persisted long into autumn 2018 (November), and started early in spring 2019 (April). We found excessive phosphorus (P) concentrations throughout the year. At high flow in winter, P desorption from sediments fostered high P concentrations in the surface waters. We lead this back to the natural catchment-specific geochemical constraints of sediment P reactions (dilution- and pH-driven). Under natural conditions, the temporal dynamics of these constraints most likely led to high P concentrations, but probably did not cause algae blooms. Since the construction of a dammed reservoir, frequent algae blooms with sporadic fish kills have been occurring. Thus, management should focus less on reducing catchment P concentrations, but on counteracting summerly dissolved oxygen (DO) depletion in the reservoir. Particular attention should be paid to the monitoring and control of sediment P concentrations, especially under climate change.

Antibody titers against a viral pathogen are typically measured using an antigen binding assay, such as an enzyme-linked immunosorbent assay (ELISA), which only measures the ability of antibodies to identify a viral antigen of interest. Neutralization assays measure the presence of virus-neutralizing antibodies in a sample. Traditional neutralization assays, such as the plaque reduction neutralization test (PRNT), are often difficult to use on a large scale due to being both labor and resource intensive. Here we describe an Ebola virus fluorescence reduction neutralization assay (FRNA), which tests for neutralizing antibodies, that requires only a small volume of sample in a 96-well format and is easy to automate. The readout of the FRNA is the percentage of Ebola virus-infected cells measured with an optical reader or overall chemiluminescence that can be generated by multiple reading platforms. Using blinded human clinical samples (EVD survivors or contacts) obtained in Liberia during the 2013-2016 Ebola virus disease outbreak, we demonstrate there was a high degree of agreement between the FRNA-measured antibody titers and the Filovirus Animal Non-clinical Group (FANG) ELISA titers with the FRNA providing information on the neutralizing capabilities of the antibodies.

PurposeThe Ponseti Method has dramatically altered the management of clubfoot, with particular implications for limited-resource settings. We sought to describe outcomes of care and risk factors for sub-optimal results using the Ponseti Method in Haiti.MethodsWe conducted a records review of patients presenting from 2011-2015 to a CURE Clubfoot clinic in Port-au-Prince, Haiti. We report patient characteristics (demographics and clinical), treatment patterns (cast number/duration and tenotomy rates), and outcomes (relapse and complications). We compared treatment with benchmarks in high-income nations and used generalized linear models to identify risk factors for delayed presentation, increased number of casts, and relapse.ResultsAmongst 168 children, age at presentation ranged from 0 days (birth) to 4.4 years, 62% were male, 35% were born at home, 63% had bilateral disease, and 46% had idiopathic clubfeet. Prior treatment (RR 6.33, 95% CI 3.18-12.62) was associated with a higher risk of delayed presentation. Risk factors for requiring ≥ 10 casts included having a non-idiopathic diagnosis (RR 2.28, 95% CI 1.08-4.83) and higher Pirani score (RR 2.78 per 0.5 increase, 95% CI 1.17-6.64). Female sex (RR 1.54, 95% CI 1.01-2.34) and higher Pirani score (RR 1.09 per 0.5 increase, 95% CI 1.00-1.17) were risk factors for relapse. Compared to North American benchmarks, children presented later (median 4.1 wks [IQR 1.6-18.1] vs. 1 wk), with longer casting (12.5 wks [SD 9.8] vs. 7.1 wks), and higher relapse (43% vs. 22%).ConclusionsHigher Pirani score, prior treatment, non-idiopathic diagnosis, and female sex were associated with a higher risk of sub-optimal outcomes in this low-resource setting. Compared to high-income nations, serial casting began later, with longer duration and higher relapse. Identifying patients at risk for poor outcomes in a low-resource setting can guide counseling, program development, and resource allocation.

Favourable body composition has been associated with higher dietary protein intake. However, little is known regarding this relationship in a population of Chinese Americans (CHA), who have lower BMI compared with other populations. The aim of the present study was to assess the relationship between dietary protein intake, fat mass (FM) and fat-free mass (FFM) in CHA. Data were from the Chinese American Cardiovascular Health Assessment (CHA CHA) 2010–2011 (n 1707); dietary intake was assessed using an adapted and validated FFQ. Body composition was assessed using bioelectrical impedance analysis. The associations between protein intake (% energy intake) and BMI, percentage FM (FM%), percentage FFM (FFM%), FM index (FMI) and FFM index (FFMI) were examined using multiple linear regression adjusted for age, sex, physical activity, acculturation, total energy intake, sedentary time, smoking status, education, employment and income. There was a significant positive association between dietary protein and BMI (B = 0·056, 95 % CI 0·017, 0·104; P = 0·005), FM (B = 0·106, 95 % CI 0·029, 0·184; P = 0·007), FM% (B = 0·112, 95 % CI 0·031, 0·194; P = 0·007) and FMI (B = 0·045, 95 % CI 0·016, 0·073; P = 0·002). There was a significant negative association between dietary protein and FFM% (B = −0·116, 95 % CI −0·196, −0·036; P = 0·004). In conclusion, higher dietary protein intake was associated with higher adiposity; however, absolute FFM and FFMI were not associated with dietary protein intake. Future work examining the relationship between protein source (i.e. animal) and body composition is warranted in this population of CHA.

Summary: Circadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults and plays a critical role in brain health and disease. We report that the core circadian clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism and a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation and inflammatory gene expression in vitro and in vivo, mediated in part by suppression of glutathione-S-transferase signaling. Functionally, loss of Bmal1 in astrocytes promotes neuronal death in vitro. Our results demonstrate that the core clock protein BMAL1 regulates astrocyte activation and function in vivo, elucidating a mechanism by which the circadian clock could influence many aspects of brain function and neurological disease. : Lananna et al. show that the circadian clock protein BMAL1 regulates astrocyte activation via a cell-autonomous mechanism involving diminished glutathione-S-transferase signaling. This finding elucidates a function of the core circadian clock in astrocytes and reveals BMAL1 as a modulator of astrogliosis. Keywords: astrocyte, circadian, astrogliosis, Bmal1, rhythm, neuroinflammation, glutathione

The immune system is increasingly recognized for its role in the genesis and progression of hypertension. The adrenal gland is a major site that coordinates the stress response via the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal system. Catecholamines released from the adrenal medulla function in the neuro-hormonal regulation of blood pressure and have a well-established link to hypertension. The immune system has an active role in the progression of hypertension and cytokines are powerful modulators of adrenal cell function. Adrenal medullary cells integrate neural, hormonal, and immune signals. Changes in adrenal cytokines during the progression of hypertension may promote blood pressure elevation by influencing catecholamine biosynthesis. This review highlights the potential interactions of cytokine signaling networks with those of catecholamine biosynthesis within the adrenal, and discusses the role of cytokines in the coordination of blood pressure regulation and the stress response.

Metabarcoding of marine environmental DNA (eDNA), originating from tissue, cells, or extracellular DNA, offers the opportunity to survey the biological composition of communities across multiple trophic levels from a non-invasive seawater sample. Here we compare results of eDNA metabarcoding of multiple trophic levels from individual seawater samples collected from a kelp forest in Monterey Bay, California in order to establish methods for future cross-trophic level eDNA analysis. Triplicate 1 L water samples were filtered using five different 47 mm diameter membrane filters (PVDF, PES, GFF, PCTE, and NC) and DNA was extracted from triplicates of each filter-type using three widely-used extraction methods (the DNeasy Blood and Tissue kit, the MoBio PowerWater DNA Isolation kit, and standard phenol/chloroform methods) resulting in 45 individual eDNA samples prepared with 15 workflow combinations. Each DNA extract was amplified using PCR primers for the 16S rRNA gene (microorganisms; Bacteria and Archaea), 18S rRNA gene (phytoplankton), and the 12S rRNA gene (vertebrates), and PCR products were sequenced on an Illumina MiSeq platform. The richness and community composition of microbial, phytoplankton, and vertebrate OTUs were not significantly different between any of the 0.2 μm pore-size filter types extracted with the DNeasy or MoBio kits. However, phenol/chloroform extraction resulted in significantly different community structures. This study provides insight into multiple choices for extraction and filtration methods to use eDNA metabarcoding for biodiversity assessment of multiple trophic levels from a single sample. We recommend any combination of either DNeasy or MoBio with PES, PCTE, PVDF, or NC filters for a cross trophic level comparison.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus capable of causing a severe hemorrhagic fever disease in humans. There are currently no licensed vaccines to prevent CCHFV-associated disease. We developed a DNA vaccine expressing the M-segment glycoprotein precursor gene of CCHFV and assessed its immunogenicity and protective efficacy in two lethal mouse models of disease: type I interferon receptor knockout (IFNAR-/-) mice; and a novel transiently immune suppressed (IS) mouse model. Vaccination of mice by muscle electroporation of the M-segment DNA vaccine elicited strong antigen-specific humoral immune responses with neutralizing titers after three vaccinations in both IFNAR-/- and IS mouse models. To compare the protective efficacy of the vaccine in the two models, groups of vaccinated mice (7-10 per group) were intraperitoneally (IP) challenged with a lethal dose of CCHFV strain IbAr 10200. Weight loss was markedly reduced in CCHFV DNA-vaccinated mice as compared to controls. Furthermore, whereas all vector-control vaccinated mice succumbed to disease by day 5, the DNA vaccine protected >60% of the animals from lethal disease. Mice from both models developed comparable levels of antibodies, but the IS mice had a more balanced Th1/Th2 response to vaccination. There were no statistical differences in the protective efficacies of the vaccine in the two models. Our results provide the first comparison of these two mouse models for assessing a vaccine against CCHFV and offer supportive data indicating that a DNA vaccine expressing the glycoprotein genes of CCHFV elicits protective immunity against CCHFV.

There are relatively few experimental studies and risk assessments of the effects on non-target insects from ultra-low volume (ULV) insecticides used for management of adult mosquitoes. Therefore, we evaluated factors that may influence the ability of an insect to intercept the insecticide at the time of application by using Hippodamia convergens (Coleoptera: Coccinellidae) in field bioassay experiments in 2011 and 2015. Treatment factors included different distances, two cage heights (ground-level and 1.5 m above ground) to the point of the application, and covered vs. uncovered cage faces (2015 only). Insecticides used included a water-based formulation (Aqua-Reslin®) and an oil-based formulation (Permanone® 30-30) of permethrin. Cage height was highly significant both years, with much less acute (i.e., short-term exposure) mortality at ground-level compared with 1.5 m. In 2011, acute mortality was less at ground-level (mean = 3.2%, median = 0%) compared to 1.5 m (mean = 85.2%, median = 100%). Cage type also was highly significant, with less mortality in covered cages compared to uncovered cages. Mortality by cage height and cage type was as follows: ground level, covered cage (mean = 2.8%, median = 0.1%); ground level, uncovered cage (mean = 41.9%, median = 9.6%); 1.5 m, covered cage (mean = 6.8%, median = 0%); 1.5 m, uncovered cage (mean = 83.7%, median = 100%). Results suggest that acute mortality to non-target insects may vary considerably based on their height and their ability to directly intercept the insecticide as the aerosol passes through the area being sprayed.

PurposeModel-constrained reconstruction with Fourier-based undersampling (MoReFUn) is introduced to accelerate the acquisition of dynamic MRI using hyperpolarized [1-13 C]-pyruvate.MethodsThe MoReFUn method resolves spatial aliasing using constraints introduced by a pharmacokinetic model that describes the signal evolution of both pyruvate and lactate. Acceleration was evaluated on three single-channel data sets: a numerical digital phantom that is used to validate the accuracy of reconstruction and model parameter restoration under various SNR and undersampling ratios, prospectively and retrospectively sampled data of an in vitro dynamic multispectral phantom, and retrospectively undersampled imaging data from a prostate cancer patient to test the fidelity of reconstructed metabolite time series.ResultsAll three data sets showed successful reconstruction using MoReFUn. In simulation and retrospective phantom data, the restored time series of pyruvate and lactate maintained the image details, and the mean square residual error of the accelerated reconstruction increased only slightly (

In the originally published version of this Article, an incorrect grant number, RO1 NS083549, was acknowledged. The correct grant number is RO1 AR055685. This error has now been corrected in both the PDF and HTML versions of the Article.

In the last two decades, genetic and genomic studies have revealed the astonishing diversity and ubiquity of microorganisms. Emergence and expansion of the human microbiome project has reshaped our thinking about how microbes control host health – not only as pathogens, but also as symbionts. In coral reef environments, scientists have begun to examine the role that microorganisms play in coral life history. Herein we review the current literature on coral-microbe interactions within the context of their role in evolution, development, and ecology. We ask the following questions, first posed by McFall-Ngai et al., 2013 in their review of animal evolution, with specific attention to how coral-microbial interactions may be affected under future environmental conditions: 1) How do corals and their microbiome affect each other’s genomes? 2) How does coral development depend on microbial partners? 3) How is homeostasis maintained between corals and their microbial symbionts? 4) How can ecological approaches deepen our understanding of the multiple levels of coral-microbial interactions? Elucidating the role that microorganisms play in the structure and function of the holobiont is essential for understanding how corals maintain homeostasis and acclimate to changing environmental conditions.

Echinoderms, positioned taxonomically at the base of deuterostomes, provide an important system for the study of the evolution of the immune system. However, there is little known about the cellular components and genes associated with echinoderm immunity. The 2013-2014 sea star wasting disease outbreak is an emergent, rapidly spreading disease, which has led to large population declines of asteroids in the North American Pacific. While evidence suggests that the signs of this disease, twisting arms and lesions, may be attributed to a viral infection, the host response to infection is still poorly understood. In order to examine transcriptional responses of the sea star Pycnopodia helianthoides to sea star wasting disease, we injected a viral sized fraction (0.2 μm) homogenate prepared from symptomatic P. helianthoides into apparently healthy stars. Nine days following injection, when all stars were displaying signs of the disease, specimens were sacrificed and coelomocytes were extracted for RNA-seq analyses. A number of immune genes, including those involved in Toll signaling pathways, complement cascade, melanization response, and arachidonic acid metabolism, were differentially expressed. Furthermore, genes involved in nervous system processes and tissue remodeling were also differentially expressed, pointing to transcriptional changes underlying the signs of sea star wasting disease. The genomic resources presented here not only increase understanding of host response to sea star wasting disease, but also provide greater insight into the mechanisms underlying immune function in echinoderms.