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Presented here are NOEMA interferometric observations of the neighboring hot cores W3(H _2 O) and W3(OH). The presence of two star-forming cores at different evolutionary stages within the same parent cloud presents a unique opportunity to study how the physics of the source and its evolutionary stage impact the chemistry. Through spectral analysis and imaging, we identify over 20 molecules in these cores. Most notably, we have detected HDO and CH _3 CH _2 CN in W3(OH), which were previously not detected in this core. We have imaged the molecular emission, revealing new structural features within these sources. W3(OH) shows absorption in a “dusty cocoon” surrounded by molecular emission. These observations also reveal extended emission that is potentially indicative of a low-velocity shock. From the information obtained herein, we have constructed column density and temperature maps for methanol and compared this information to the molecular images. By comparing the spatial distribution of molecules that may be destroyed at later stages of star formation, this work demonstrates the impact of physical environment on chemistry in star-forming regions at different evolutionary stages.

European heritage breeds, such as the Blonde (B), Red (R), and Swallow-bellied (SB) Mangalica pig, display an extreme propensity to fatten and are reputed to produce superior quality pork. This suggests that Mangalica pork should command a higher price, and the Mangalica is a candidate breed to target niche markets within the United States. Our objectives were to test this hypothesis by (1) directly comparing growth performance and carcass merit of purebred Yorkshire (Y), B, R, and SB Mangalica pigs to identify the best breed for adoption, and (2) comparing indices of pork quality in purebred R, Y, and crossbred (R × Y) pigs to determine if crossbreeding represented a viable alternative to the adoption of purebred Mangalica. Daily feed intake, average daily gain (ADG), and feed efficiency were highest in Y and lowest in SB pigs with B and R ranked intermediately (p < 0.001). Backfat thickness was greatest in B and lowest in Y with R and SB ranked intermediately (p < 0.001). Marbling score was greatest in R pigs and lowest in Y pigs with B and SB ranked intermediately (p < 0.01). In contrast, loin eye area (LEA) was greatest in Y pigs compared to B, R, and SB (p < 0.001). Indices of meat quality were then compared in R, R × Y, and Y pigs. Backfat thickness and marbling scores were greater in R than R × Y and Y pigs (p < 0.001) while LEA was greater in Y than R × Y and R pigs (p < 0.001). Loin and ham ultimate pH, color, and firmness scores were significantly greater in R than R × Y or Y pigs (p < 0.05). Meanwhile, cook loss was significantly less in R than Y pigs (p < 0.007) while Warner-Bratzler Shear Force (WBS) was not different in chops between groups (p < 0.11). These data indicate that though Mangalica exhibit poorer growth performance, Mangalica pork exhibits superior pork quality attributes, suggesting that higher price points for Mangalica pork in niche markets are justified.

Spinal direct current stimulation (sDCS) modulates motoneuron (MN) excitability beyond the stimulation period, making it a potential neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS), a MN degenerative disease in which MN excitability dysfunction plays a critical and complex role. Recent evidence confirms induced changes in MN excitability via measured MN electrophysiological properties in the SOD1 ALS mouse during and following invasive subcutaneous sDCS (ssDCS). The first aim of our pilot study was to determine the clinical potential of these excitability changes at symptom onset (P90-P105) in ALS via a novel non-invasive transcutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice. The primary outcomes were motor function and survival. Unfortunately, skin damage avoidance limited the strength of applied stimulation intensity, likewise limiting measurable primary effects. The second aim of this study was to determine which orientation of stimulation (anodal vs cathodal, which are expected to have opposing effects) is beneficial vs harmful in ALS. Despite the lack of measured primary effects, strong trends in survival of the anodal stimulation group, combined with an analysis of survival variance and correlations among symptoms, suggest anodal stimulation is harmful at symptom onset. Therefore, cathodal stimulation may be beneficial at symptom onset if a higher stimulation intensity can be safely achieved via subcutaneously implanted electrodes or alternative methods. Importantly, the many logistical, physical, and stimulation parameters explored in developing this novel non-invasive treatment paradigm on unanesthetized mice provide insight into an appropriate and feasible methodology for future tsDCS study designs and potential clinical translation.

Methicillin-resistant Staphylococcus aureus (MRSA) represents one of the most serious infectious disease concerns worldwide, with the CDC labeling it a “serious threat” in 2019. The current arsenal of antibiotics works by targeting bacterial growth and survival, which exerts great selective pressure for the development of resistance. The development of novel anti-infectives that inhibit quorum sensing and thus virulence in MRSA has been recurrently proposed as a promising therapeutic approach. In a follow-up of a study examining the MRSA quorum sensing inhibitory activity of extracts of Italian plants used in local traditional medicine, 224C-F2 was reported as a bioactive fraction of a Castanea sativa (European chestnut) leaf extract. The fraction demonstrated high activity in vitro and effective attenuation of MRSA pathogenicity in a mouse model of skin infection. Through further bioassay-guided fractionation using reverse-phase high performance liquid chromatography, a novel hydroperoxy cycloartane triterpenoid, castaneroxy A (1), was isolated. Its structure was established by nuclear magnetic resonance, mass spectrometry and X-ray diffraction analyses. Isomers of 1 were also detected in an adjacent fraction. In a series of assays assessing inhibition of markers of MRSA virulence, 1 exerted activities in the low micromolar range. It inhibited agr::P3 activation (IC50 = 31.72 µM), δ-toxin production (IC50 = 31.72 µM in NRS385), supernatant cytotoxicity to HaCaT human keratinocytes (IC50 = 7.93 µM in NRS385), and rabbit erythrocyte hemolytic activity (IC50 = 7.93 µM in LAC). Compound 1 did not inhibit biofilm production, and at high concentrations it exerted cytotoxicity against human keratinocytes greater than that of 224C-F2. Finally, 1 reduced dermonecrosis in a murine model of MRSA infection. The results establish 1 as a promising antivirulence candidate for development against MRSA.

Abstract The COVID‐19 pandemic is a public health crisis, having killed more than 514 000 US adults as of March 2, 2021. COVID‐19 mitigation strategies have unintended consequences on managing chronic conditions such as hypertension, a leading cause of cardiovascular disease and health disparities in the United States. During the first wave of the pandemic in the United States, the combination of observed racial/ethnic inequities in COVID‐19 deaths and social unrest reinvigorated a national conversation about systemic racism in health care and society. The 4th Annual University of Utah Translational Hypertension Symposium gathered frontline clinicians, researchers, and leaders from diverse backgrounds to discuss the intersection of these 2 critical social and public health phenomena and to highlight preexisting disparities in hypertension treatment and control exacerbated by COVID‐19. The discussion underscored environmental and socioeconomic factors that are deeply embedded in US health care and research that impact inequities in hypertension. Structural racism plays a central role at both the health system and individual levels. At the same time, virtual healthcare platforms are being accelerated into widespread use by COVID‐19, which may widen the divide in healthcare access across levels of wealth, geography, and education. Blood pressure control rates are declining, especially among communities of color and those without health insurance or access to health care. Hypertension awareness, therapeutic lifestyle changes, and evidence‐based pharmacotherapy are essential. There is a need to improve the implementation of community‐based interventions and blood pressure self‐monitoring, which can help build patient trust and increase healthcare engagement.

Lesbian, Gay, Bisexual, Transgender, Queer, and other sexual and gender minority (LGBTQ+) youth and young adults (YYAs) have poorer mental health outcomes than their cisgender, heterosexual peers in large part due to multilevel stigmatization and minority stress. This was exacerbated by psychological stressors stemming from the COVID-19 pandemic; these experiences intersected with YYA unique developmental stage. Here we explored LGBTQ+ YYA's pandemic-related experiences, focusing on intersections between stigma and belonging, developmental processes, and their relationship to mental health. We conducted qualitative interviews from August to November 2021 with 34 LGBTQ+ YYA ages 14 to 24; interviews were nested within a quantitative study on YYA experiences during COVID-19. Interviews were transcribed and coded using thematic analysis. YYA described how pandemic impacts like quarantine and isolation directly impacted their mental health; these coalesced around four types of thematic shifts: shifts in (1) time; (2) living situations; (3) community supports; and (4) social and political climate. Multilevel stigmatization also created new mechanisms of norm enforcement for LGBTQ+ YYA. Interviews demonstrated how the pandemic also impacted key developmental processes including identity formation and autonomy seeking. The potential consequences of these pandemic-related shifts largely depended on YYA's experiences of stigma and/or belonging throughout the pandemic. Findings suggested that isolation from the COVID-19 pandemic intersected with existing socio-ecological structures in LGBTQ+ young people's lives. Efforts to investigate longitudinal impacts of the pandemic, as well as to intervene to reduce the stigmatization experienced by LGBTQ+ YYA, remain urgent.

School-based mental health professionals consistently report that they are either not prepared to support grieving students, or do not have time to integrate crisis intervention support into their hectic schedule. Given that inadequate school mental health services can increase a bereaved student's risk of developing emotional problems, it is critical that school psychologists increase their comfort in grief. This study surveyed 75 school psychologists in the Northwestern United States regarding their training and experience in grief support. A reflexive thematic analysis identified four themes related to the challenges and recommendations in grief support: lack of training, limited role of the school psychologist, lack of formalized grief response system, and lack of school and community resources. Furthermore, only 3% of participants reported taking the lead in providing grief support and 64% provide grief support fewer than five times a year. The majority (81%) reported that they had zero courses devoted to grief support during their graduate degree, with more participants (67%) obtaining grief training postdegree. Study limitations, areas for further research, and implications for schools and school psychologists are also discussed.

Abstract Background Central cancer registries are often used to survey population-based samples of cancer survivors. These surveys are typically administered via paper or telephone. In most populations, web surveys obtain much lower response rates than paper surveys. This study assessed the feasibility of web surveys for collecting patient-reported outcomes via a central cancer registry. Methods Potential participants were sampled from Utah Cancer Registry records. Sample members were randomly assigned to receive a web or paper survey, and then randomized to either receive or not receive an informative brochure describing the cancer registry. We calculated adjusted risk ratios with 95% confidence intervals to compare response likelihood and the demographic profile of respondents across study arms. Results The web survey response rate (43.2%) was lower than the paper survey (50.4%), but this difference was not statistically significant (adjusted risk ratio = 0.88, 95% confidence interval = 0.72, 1.07). The brochure also did not significantly influence the proportion responding (adjusted risk ratio = 1.03, 95% confidence interval = 0.85, 1.25). There were few differences in the demographic profiles of respondents across the survey modes. Older age increased likelihood of response to a paper questionnaire but not a web questionnaire. Conclusions Web surveys of cancer survivors are feasible without significantly influencing response rates, but providing a paper response option may be advisable particularly when surveying older individuals. Further examination of the varying effects of brochure enclosures across different survey modes is warranted.

Abstract Introduction The purpose of this study was to evaluate intraocular pressure (IOP) lowering and safety of XEN® stent in medically refractory, progressive, open-angle glaucoma (OAG). Methods Forty-seven eyes of 42 patients were treated with XEN® stent alone or combined with phacoemulsification. Results Mean IOP decreased from 22.34 ± 7.34 mmHg to 12.91 ± 4.21, 12.95 ± 4.36, 13.49 ± 3.91, and 13.36 ± 3.63 mmHg at 1, 3, 6, and 12 months (95% confidence interval [CI] [20.24, 24.44], [11.71, 14.12], [11.63, 14.27], [12.36, 14.62], and [12.10, 14.62]), respectively. Mean number of medications decreased from 2.96 ± 1.20 (95% CI [2.62, 3.30]) at baseline to 0.75 ± 1.27 (95% CI [0.31, 1.19]) at 1 year. At 1 year (n = 32), complete success was achieved in 68.8% (n = 22/32) (i.e., IOP reduction ≥ 20% and IOP

Abstract Laccases are multicopper oxidases that are being studied for their potential application in pretreatment strategies of lignocellulosic feedstocks for bioethanol production. Here, we report the expression and characterization of a predicted laccase (LAC_2.9) from the thermophilic bacterial strain Thermus sp. 2.9 and investigate its capacity to delignify lignocellulosic biomass. The purified enzyme displayed a blue color typical of laccases, showed strict copper dependence and retained 80% of its activity after 16 h at 70 °C. At 60 °C, the enzyme oxidized 2,2′-azino-di-(3-ethylbenzthiazoline sulfonate) (ABTS) and 2,6-dimethoxyphenol (DMP) at optimal pH of 5 and 6, respectively. LAC_2.9 had higher substrate specificity (k cat/K M) for DMP with a calculated value that accounts for one of the highest reported for laccases. Further, the enzyme oxidized a phenolic lignin model dimer. The incubation of steam-exploded eucalyptus biomass with LAC_2.9 and 1-hydroxybenzotriazole (HBT) as mediator changed the structural properties of the lignocellulose as evidenced by Fourier transform infrared (FTIR) spectroscopy and thermo-gravimetric analysis (TGA). However, this did not increase the yield of sugars released by enzymatic saccharification. In conclusion, LAC_2.9 is a thermostable laccase with potential application in the delignification of lignocellulosic biomass.

Summary Stem cells are unique cell populations able to copy themselves exactly as well as specialize into new cell types. Stem cells isolated from early stages of embryo development are pluripotent, i.e., can be differentiated into multiple different cell types. In addition, scientists have found a way of reverting specialized cells from an adult into an embryonic‐like state. These cells, that are as effective as cells isolated from early embryos, are termed induced pluripotent stem cells (iPSCs). The potency of iPSC technology is recently being employed by researchers aimed at helping wildlife and environmental conservation efforts. Ambitious attempts using iPSCs are being made to preserve endangered animals as well as reanimate extinct species, merging science fiction with reality. Other research to sustain natural resources and promote animal welfare are exploring iPSCs for laboratory grown animal products without harm to animals offering unorthodox options for creating meat, leather, and fur. There is great potential in iPSC technology and what can be achieved in consumerism, animal welfare, and environmental protection and conservation. Here, we discuss current research in the field of iPSCs and how these research groups are attempting to achieve their goals. Stem Cells Translational Medicine 2019;8:7–13

The success of performance in basketball relies on both optimal body composition and nutrient intake. The purpose of this study was to examine seasonal changes in body composition (BC), resting metabolic rate (RMR) and respiratory quotient (RQ), as well as dietary intake of National Collegiate Athletic Association (NCAA) Division I (DI) male basketball players. BC, RMR and RQ were assessed during pre-season, in-season, and post-season (September, December, and March) while dietary assessment data were collected in September and February. Results of this study indicated that players received inadequate energy (p < 0.0001), protein (p < 0.001) and carbohydrate (p < 0.0001) relative to the recommendations for exercising individuals during the September baseline period. However, following diet analysis and consultations and relative to recommendations, athletes received adequate amounts of energy and protein during follow-up, yet intakes of carbohydrate (p = 0.0025) were still significantly different than recommended. Results also indicated that there was a decrease in percent body fat (%BF) during season, an increase in lean body mass (LBM) from pre- to post-season, a peak in RMR during season and an increase in RQ post-season. These findings reveal that significant metabolic and body composition changes occur in players over the season and suggest that nutritional strategies employed concomitantly may be beneficial.

Microbial interactions in harmful algal bloom (HAB) communities have been examined in marine systems, but are poorly studied in fresh waters. To investigate HAB-microbe interactions, we isolated bacteria with close associations to bloom-forming cyanobacteria, Microcystis spp., during a 2017 bloom in the western basin of Lake Erie. The genomes of five isolates (Exiguobacterium sp. JMULE1, Enterobacter sp. JMULE2, Deinococcus sp. JMULE3, Paenibacillus sp. JMULE4, and Acidovorax sp. JMULE5.) were sequenced on a PacBio Sequel system. These genomes ranged in size from 3.1 Mbp (Exiguobacterium sp. JMULE1) to 5.7 Mbp (Enterobacter sp. JMULE2). The genomes were analyzed for genes relating to critical metabolic functions, including nitrogen reduction and carbon utilization. All five of the sequenced genomes contained genes that could be used in potential signaling and nutrient exchange between the bacteria and cyanobacteria such as Microcystis. Gene expression signatures of algal-derived carbon utilization for two isolates were identified in Microcystis blooms in Lake Erie and Lake Tai (Taihu) at low levels, suggesting these organisms are active and may have a functional role during Microcystis blooms in aggregates, but were largely missing from whole water samples. These findings build on the growing evidence that the bacterial microbiome associated with bloom-forming algae have the functional potential to contribute to nutrient exchange within bloom communities and interact with important bloom formers like Microcystis.

Vitamin D is well known for its traditional role in bone mineral homeostasis; however, recent evidence suggests that vitamin D also plays a significant role in metabolic control. This study served to investigate putative linkages between vitamin D deficiency (VDD) and metabolic disruption of bioactive lipids by MS imaging. Our approach employed infrared-matrix-assisted laser desorption electrospray ionization MS imaging for lipid metabolite profiling in 6-month-old zebrafish fed either a VDD or a vitamin D-sufficient (VDS) diet. Using a lipidomics pipeline, we found that VDD zebrafish had a greater abundance of bioactive lipids (N-acyls, endocannabinoids [ECs], diacylglycerols/triacylglycerols, bile acids/bile alcohols, and vitamin D derivatives) suggestive of increased EC tone compared with VDS zebrafish. Tandem MS was performed on several differentially expressed metabolites with sufficient ion abundances to aid in structural elucidation and provide additional support for MS annotations. To confirm activation of the EC pathways, we subsequently examined expression of genes involved in EC biosynthesis, metabolism, and receptor signaling in adipose tissue and liver from VDD and VDS zebrafish. Gene expression changes were congruent with increased EC tone, with VDD zebrafish demonstrating increased synthesis and metabolism of anandamide compared with VDS zebrafish. Taken together, our data suggest that VDD may promote accumulation of bioactive lipids and increased EC tone in zebrafish.

One method for the evaluation of sensorimotor therapeutic interventions, the horizontal ladder walking task, analyzes locomotor changes that may occur after disease, injury, or by external manipulation. Although this task is well suited for detection of large effects, it may overlook smaller changes. The inability to detect small effect sizes may be due to a neural compensatory mechanism known as "cross limb transfer", or the contribution of the contralateral limb to estimate an injured or perturbed limb's position. The robust transfer of compensation from the contralateral limb may obscure subtle locomotor outcomes that are evoked by clinically relevant therapies, in the early onset of disease, or between higher levels of recovery. Here, we propose angled rungs as a novel modification to the horizontal ladder walking task. Easily-adjustable angled rungs force rats to locomote across a different locomotion path for each hindlimb and may therefore make information from the contralateral limb less useful. Using hM3Dq (excitatory) Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) expressed in large diameter peripheral afferents of the hindlimb in the intact animal, we characterized the sensitivity of our design to detect stepping differences by comparing locomotor changes observed on angled rungs to those observed on a standard horizontal ladder. On our novel asymmetrical ladder, activation of DREADDs resulted in significant differences in rung misses (p = 0.000011) and weight-supporting events (p = 0.049). By comparison, on a standard ladder, we did not observe differences in these parameters (p = 0.86 and p = 0.98, respectively). Additionally, no locomotor differences were detected in baseline and inactivated DREADDs trials when we compared ladder types, suggesting that the angled rungs do not change animal gait behavior unless intervention or injury is introduced. Significant changes observed with angled rungs may demonstrate more sensitive probing of locomotor changes due to the decoupling of cross limb transfer.

Candida albicans is a commensal member of the human microbiota that colonizes multiple niches in the body including the skin, oral cavity, and gastrointestinal and genitourinary tracts of healthy individuals. It is also the most common human fungal pathogen isolated from patients in clinical settings. C. albicans can cause a number of superficial and invasive infections, especially in immunocompromised individuals. The ability of C. albicans to succeed as both a commensal and a pathogen, and to thrive in a wide range of environmental niches within the host, requires sophisticated transcriptional regulatory programs that can integrate and respond to host specific environmental signals. Identifying and characterizing the transcriptional regulatory networks that control important developmental processes in C. albicans will shed new light on the strategies used by C. albicans to colonize and infect its host. Here, we discuss the transcriptional regulatory circuits controlling three major developmental processes in C. albicans: biofilm formation, the white-opaque phenotypic switch, and the commensal-pathogen transition. Each of these three circuits are tightly knit and, through our analyses, we show that they are integrated together by extensive regulatory crosstalk between the core regulators that comprise each circuit.

Our skin is our first line of defense against environmental and pathogenic challenges. It is densely populated by a flora of bacteria, fungi, and viruses that normally interact with each other and with our immune system to promote skin health and homeostasis. Staphylococcus epidermidis is one of the most abundant bacterial colonizers of healthy human skin. While the field has historically assumed that all S. epidermidis isolates behave similarly, emerging evidence suggests that colonization by specific strains of S. epidermidis can either help or hurt the skin barrier depending on the context. In this short review, we discuss what is currently understood about S. epidermidis strain-level diversity and evaluate costs and benefits of S. epidermidis skin colonization. We challenge the current dogma that "all S. epidermidis strains behave equally" and posit that behavior is in fact highly context and strain dependent. Finally, in light of current proposals to use skin commensals as nonantibiotic treatments for acute or chronic skin diseases, we conclude that more work is urgently needed to fully understand the pathogenic and protective roles of commensals before we use them therapeutically.

Abstract Growth monitoring and promotion (GMP) is both a service for diagnosing inadequate child growth in its earliest stages and a delivery platform for nutrition counselling. The widespread use of GMP services in developing countries has the potential to substantially reduce persistent child undernutrition through early diagnosis and by linking caregivers and their children to key health and nutrition services. However, researchers have questioned the effectiveness of GMP services, which are frequently undermined by underdeveloped health systems and inconsistent implementation. This analysis examined both supply‐ and demand‐side factors for GMP utility in Nepal from the perspectives of beneficiaries and service providers, particularly focusing on three components of GMP: growth assessment, analysis of growth status and counselling. The most common factors influencing GMP uptake included beneficiaries' perceptions of the relative importance of GMP and the knowledge and skill of frontline workers. Both providers and beneficiaries viewed GMP as a secondary health and nutrition activity and therefore less important than curative services. We found deficits in GMP‐related knowledge and skills among providers (i.e. health workers and female community health volunteers), as well as indications of poor training quality and coverage. Furthermore, we found variation in GMP utilization by maternal age, education and residency (alone, nuclear or extended), as well as household socio‐economic well‐being and rurality. This study is the first to assess factors influencing both beneficiaries and service providers for GMP utilization. Further research is needed to explore the implementation of improved GMP protocols and to evaluate facility‐level implementation barriers.

ABSTRACT Water bloom development due to eutrophication constitutes a case of niche specialization among planktonic cyanobacteria, but the genomic repertoire allowing bloom formation in only some species has not been fully characterized. We posited that the habitat relevance of a trait begets its underlying genomic complexity, so that traits within the repertoire would be differentially more complex in species successfully thriving in that habitat than in close species that cannot. To test this for the case of bloom-forming cyanobacteria, we curated 17 potentially relevant query metabolic pathways and five core pathways selected according to existing ecophysiological literature. The available 113 genomes were split into those of blooming (45) or nonblooming (68) strains, and an index of genomic complexity for each strain’s version of each pathway was derived. We show that strain versions of all query pathways were significantly more complex in bloomers, with complexity in fact correlating positively with strain blooming incidence in 14 of those pathways. Five core pathways, relevant everywhere, showed no differential complexity or correlations. Gas vesicle, toxin and fatty acid synthesis, amino acid uptake, and C, N, and S acquisition systems were most strikingly relevant in the blooming repertoire. Further, we validated our findings using metagenomic gene expression analyses of blooming and nonblooming cyanobacteria in natural settings, where pathways in the repertoire were differentially overexpressed according to their relative complexity in bloomers, but not in nonbloomers. We expect that this approach may find applications to other habitats and organismal groups. IMPORTANCE We pragmatically delineate the trait repertoire that enables organismal niche specialization. We based our approach on the tenet, derived from evolutionary and complex-system considerations, that genomic units that can significantly contribute to fitness in a certain habitat will be comparatively more complex in organisms specialized to that habitat than their genomic homologs found in organisms from other habitats. We tested this in cyanobacteria forming harmful water blooms, for which decades-long efforts in ecological physiology and genomics exist. Our results essentially confirm that genomics and ecology can be linked through comparative complexity analyses, providing a tool that should be of general applicability for any group of organisms and any habitat, and enabling the posing of grounded hypotheses regarding the ecogenomic basis for diversification.

Microcystins are potent hepatotoxins that are frequently detected in fresh water lakes plagued by toxic cyanobacteria. Microbial biodegradation has been referred to as the most important avenue for removal of microcystin from aquatic environments. The biochemical pathway most commonly associated with the degradation of microcystin is encoded by the mlrABCD (mlr) cassette. The ecological significance of this pathway remains unclear as no studies have examined the expression of these genes in natural environments. Six metatranscriptomes were generated from microcystin-producing Microcystis blooms and analyzed to assess the activity of this pathway in environmental samples. Seventy-eight samples were collected from Lake Erie, United States/Canada and Lake Tai (Taihu), China, and screened for the presence of mlr gene transcripts. Read mapping to the mlr cassette indicated transcripts for these genes were absent, with only 77 of the collective 3.7 billion reads mapping to any part of the mlr cassette. Analysis of the assembled metatranscriptomes supported this, with only distantly related sequences identified as mlrABC-like. These observations were made despite the presence of microcystin and over 500,000 reads mapping to the mcy cassette for microcystin production. Glutathione S-transferases and alkaline proteases have been previously hypothesized to be alternative pathways for microcystin biodegradation, and expression of these genes was detected across space and time in both lakes. While the activity of these alternative pathways needs to be experimentally confirmed, they may be individually or collectively more important than mlr genes in the natural environment. Importantly, the lack of mlr expression could indicate microcystin biodegradation was not occurring in the analyzed samples. This study raises interesting questions about the ubiquity, specificity and locality of microcystin biodegradation, and highlights the need for the characterization of relevant mechanisms in natural communities to understand the fate of microcystin in the environment and risk to public health.

In 2016, room-and-pillar mining provided nearly 40% of underground coal production in the United States. Over the past decade, rib falls have resulted in 12 fatalities, representing 28% of the ground fall fatalities in U.S. underground coal mines. Nine of these 12 fatalities (75%) have occurred in room-and-pillar mines. The objective of this research is to study the geomechanics of bench room-and-pillar mining and the associated response of high pillar ribs at overburden depths greater than 300 m. This paper provides a definition of the bench technique, the pillar response due to loading, observational data for a case history, a calibrated numerical model of the observed rib response, and application of this calibrated model to a second site. Keywords: Deep cover, Bench mining, Thick seam, Retreat mining, Rib response, Rib support

Families of quasiracemic materials constructed from 3- and 4-substituted chiral diarylamide molecular frameworks were prepared, where the imposed functional group differences systematically varied from H to CF3–9 unique components for each isomeric framework. Cocrystallization from the melt via hot stage thermomicroscopy using all possible racemic and quasiracemic combinations probed the structural boundaries of quasiracemate formation. The crystal structures and lattice energies (differential scanning calorimetry and lattice energy calculations) for many of these systems showed that quasienantiomeric components organize with near inversion symmetry and lattice energetics closely resembling those found in the racemic counterparts. This study also compared the shape space of pairs of quasienantiomers using an in silico alignment-based method to approximate the differences in molecular shape and provide a diagnostic tool for quasiracemate prediction. Comparing these results to our recent report on related 2-substituted diarylamide quasiracemates shows that functional group position can have a marked effect on quasiracemic behavior and provide critical insight to a more complete shape space, essential for defining molecular recognition processes.

Risk factors for severe COVID-19 pathology are currently being investigated worldwide. The emergence of this highly infectious respiratory disease has plagued the world, with varying severity across populations of different age, race, and socio-economic level. These data suggest that other environmental or social factors may contribute to this disease’s severity. Using a mouse model, we identify heavy alcohol and cannabinoid consumption as risk factors for increased pulmonary pathology in the setting of exposure to a microbial pulmonary pathogen (K. pneumoniae). We present observational evidence that pneumonia patients admitted to North Carolina hospitals have longer lengths of stay when they endorse alcohol use or have conditions considered alcohol attributable. We are concerned that the observed increase in alcohol and legal cannabinoid sales during lockdown and quarantine may contribute to increased pulmonary pathology among patients who become infected with COVID-19.

Why do some room and pillar retreat panels encounter abnormal conditions? What factors deserve the most consideration during the planning and execution phases of mining and what can be done to mitigate those abnormal conditions when they are encountered? To help answer these questions, and to determine some of the relevant factors influencing the conditions of room and pillar (R & P) retreat mining entries, four consecutive R & P retreat panels were evaluated. This evaluation was intended to reinforce the influence of topographic changes, depth of cover, multiple-seam interactions, geological conditions, and mining geometry. This paper details observations were made in four consecutive R & P retreat panels and the data were collected from an instrumentation site during retreat mining. The primary focus was on the differences observed among the four panels and within the panels themselves. The instrumentation study was initially planned to evaluate the interactions between primary and secondary support, but produced rather interesting results relating to the loading encountered under the current mining conditions. In addition to the observation and instrumentation, numerical modeling was performed to evaluate the stress conditions. Both the LaModel 3.0 and Rocscience Phase 2 programs were used to evaluate these four panels. The results of both models indicated a drastic reduction in the vertical stresses experienced in these panels due to the full extraction mining in overlying seams when compared to the full overburden load. Both models showed a higher level of stress associated with the outside entries of the panels. These results agree quite well with the observations and instrumentation studies performed at the mine. These efforts provided two overarching conclusions concerning R & P retreat mine planning and execution. The first was that there are four areas that should not be overlooked during R & P retreat mining: topographic relief, multiple-seam stress relief, stress concentrations near the gob edge, and geologic changes in the immediate roof. The second is that in order to successfully retreat an R & P panel, a three-phased approach to the design and analysis of the panel should be conducted: the planning phase, evaluation phase, and monitoring phase. Keywords: Room and pillar, Retreat mining, Deep cover, Safety, Multiple seam

Summary: Background: WHO recommends daily iron supplementation for pregnant women, but adherence is poor because of side-effects, effectiveness is low, and there are concerns about possible harm. The iron-regulatory hormone hepcidin can signal when an individual is ready-and-safe to receive iron. We tested whether a hepcidin-guided screen-and-treat approach to combat iron-deficiency anaemia could achieve equivalent efficacy to universal administration, but with lower exposure to iron. Methods: We did a three-arm, randomised, double-blind, non-inferiority trial in 19 rural communities in the Jarra West and Kiang East districts of The Gambia. Eligible participants were pregnant women aged 18–45 years at between 14 weeks and 22 weeks of gestation. We randomly allocated women to either WHO's recommended regimen (ie, a daily UN University, UNICEF, and WHO international multiple-micronutrient preparation [UNIMMAP] containing 60 mg iron), a 60 mg screen-and-treat approach (ie, daily UNIMMAP containing 60 mg iron for 7 days if weekly hepcidin was

The bacterial catabolism of aromatic compounds has considerable promise to convert lignin depolymerization products to commercial chemicals. Alkylphenols are a key class of depolymerization products whose catabolism is not well-elucidated. We isolated Rhodococcus rhodochrous EP4 on 4-ethylphenol and applied genomic and transcriptomic approaches to elucidate alkylphenol catabolism in EP4 and Rhodococcus jostii RHA1. RNA-Seq and RT-qPCR revealed a pathway encoded by the aphABCDEFGHIQRS genes that degrades 4-ethylphenol via the meta-cleavage of 4-ethylcatechol. This process was initiated by a two-component alkylphenol hydroxylase, encoded by the aphAB genes, which were upregulated ~3,000-fold. Purified AphAB from EP4 had highest specific activity for 4-ethylphenol and 4-propylphenol (~2,000 U/mg) but did not detectably transform phenol. Nevertheless, a ΔaphA mutant in RHA1 grew on 4-ethylphenol by compensatory upregulation of phenol hydroxylase genes (pheA1-3). Deletion of aphC, encoding an extradiol dioxygenase, prevented growth on 4-alkylphenols but not phenol. Disruption of pcaL in the β-ketoadipate pathway prevented growth on phenol but not 4-alkylphenols. Thus, 4-alkylphenols are catabolized exclusively via meta-cleavage in rhodococci while phenol is subject to ortho-cleavage. A putative genomic island encoding aph genes was identified in EP4 and several other rhodococci. Overall, this study identifies a 4-alkylphenol pathway in rhodococci, demonstrates key enzymes involved, and presents evidence that the pathway is encoded in a genomic island. These advances are of particular importance for wide-ranging industrial applications of rhodococci, including upgrading of lignocellulose biomass.

Some giant viruses are ecological agents that are predicted to be involved in the top-down control of single-celled eukaryotic algae populations in aquatic ecosystems. Despite an increased interest in giant viruses since the discovery and characterization of Mimivirus and other viral giants, little is known about their physiology and ecology. In this study, we characterized the genome and functional potential of a giant virus that infects the freshwater haptophyte Chrysochromulina parva, originally isolated from Lake Ontario. This virus, CpV-BQ2, is a member of the nucleo-cytoplasmic large DNA virus (NCLDV) group and possesses a 437 kb genome encoding 503 ORFs with a GC content of 25%. Phylogenetic analyses of core NCLDV genes place CpV-BQ2 amongst the emerging group of algae-infecting Mimiviruses informally referred to as the “extended Mimiviridae,” making it the first virus of this group to be isolated from a freshwater ecosystem. During genome analyses, we also captured and described the genomes of three distinct virophages that co-occurred with CpV-BQ2 and likely exploit CpV for their own replication. These virophages belong to the polinton-like viruses (PLV) group and encompass 19–23 predicted genes, including all of the core PLV genes as well as several genes implicated in genome modifications. We used the CpV-BQ2 and virophage reference sequences to recruit reads from available environmental metatranscriptomic data to estimate their activity in fresh waters. We observed moderate recruitment of both virus and virophage transcripts in samples obtained during Microcystis aeruginosa blooms in Lake Erie and Lake Tai, China in 2013, with a spike in activity in one sample. Virophage transcript abundance for two of the three isolates strongly correlated with that of the CpV-BQ2. Together, the results highlight the importance of giant viruses in the environment and establish a foundation for future research on the physiology and ecology CpV-BQ2 as a model system for algal Mimivirus dynamics in freshwaters.

Human-centered design provides a means to help designers create products or systems with ‘people’ as the focus. Compassionate Design (CD), introduced in this paper, is an approach that addresses niche sensitive needs and involves a way of thinking where designers pay special attention to the users’ sense of dignity, empowerment, and security. These niche needs surfaced as a result of analyses of 12 cases situated in sensitive contexts where the users felt vulnerable, had a high level of emotional engagement and were negatively affected by the situation. The designers described their deep concern for the users in various talks and interviews. This paper explains the conception of CD and its development that resulted from iteratively and qualitatively analyzing these cases in which designers were intuitively focusing on niche user needs. Dignity, empowerment and security form the basis of CD and have been contextualized in Maslow’s hierarchy of needs after they emerged as a result of the analysis of data. This research sets the platform for a design approach that can help designers to consider the often unarticulated user needs of dignity, empowerment and security, in a more intentional manner and not be left to chance.

Colonocytes possess a specific carrier-mediated uptake process for the microbiota-generated thiamin (vitamin B1) pyrophosphate (TPP) that involves the TPP transporter (TPPT; product of the SLC44A4 gene). Little is known about the effect of exogenous factors (including enteric pathogens) on the colonic TPP uptake process. Our aim in this study was to investigate the effect of Enterohemorrhagic Escherichia coli (EHEC) infection on colonic uptake of TPP. We used human-derived colonic epithelial NCM460 cells and mice in our investigation. The results showed that infecting NCM460 cells with live EHEC (but not with heat-killed EHEC, EHEC culture supernatant, or with non-pathogenic E. Coli) to lead to a significant inhibition in carrier-mediated TPP uptake, as well as in level of expression of the TPPT protein and mRNA. Similarly, infecting mice with EHEC led to a significant inhibition in colonic TPP uptake and in level of expression of TPPT protein and mRNA. The inhibitory effect of EHEC on TPP uptake by NCM460 was found to be associated with reduction in the rate of transcription of the SLC44A4 gene as indicated by the significant reduction in the activity of the SLC44A4 promoter transfected into EHEC infected cells. The latter was also associated with a marked reduction in the level of expression of the transcription factors CREB-1 and ELF3, which are known to drive the activity of the SLC44A4 promoter. Finally, blocking the ERK1/2 and NF-kB signaling pathways in NCM460 cells significantly reversed the level of EHEC inhibition in TPP uptake and TPPT expression. Collectively, these findings show, for the first time, that EHEC infection significantly inhibit colonic uptake of TPP, and that this effect appears to be exerted at the level of SLC44A4 transcription and involves the ERK1/2 and NF-kB signaling pathways.

Latino smokers in the United States (US) are known to experience smoking cessation treatment disparities due to their under-utilization of services, limited access to health care, and poor smoking cessation treatment outcomes. A limited number of studies have focused on developing and testing smoking cessation treatments for Latino smokers in the US. The objectives of this study were to conduct a feasibility pilot randomized trial testing three smoking cessation interventions for Latinos. Twenty-five adult Latino smokers were randomized to one of three groups: Culturally-Tailored Smoking Cessation plus Adherence Enhancement (CT+AE), Culturally-Tailored Smoking Cessation (CTSC), and a Health Education (HE) control group. All participants received three counseling sessions along with nicotine replacement therapy (NRT). Data relating to intervention acceptability and NRT adherence were collected. Self-reported 7-day point prevalence smoking was collected at 3 and 6 month follow-up and biochemically verified with expired carbon monoxide testing. Overall, the interventions demonstrated high levels of feasibility and acceptability. Days of nicotine patch use were found to be higher in the CT+AE group (mean (M) = 81.3;standard deviation (SD) = 3.32) than the CTSC (M = 68.6;SD = 13.66) and HE (M = 64;SD = 17.70) groups. At 3-month follow-up, approximately 50% of the CT+AE group were smoking abstinent, 25% of the CTSC group, and 44% of the HE group. At 6-month follow-up, 37.5% of the CT+AE group were abstinent, 25% of the CTSC group, and 44.4% of the HE group. This study is the first to target Latino smokers in the US with a culturally-tailored intervention that addresses treatment adherence. Results support the preliminary feasibility and acceptability of the CT+AE intervention. Trial Registration: ClinicalTrials.gov NCT02596711.

While higher education disability resource professionals are required to use considerable professional judgment to make accommodation-related decisions, there is a lack of guidance on how to make these decisions. Because disability resource professionals commonly ascribe to a "common-sense standard" when making accommodation-related decisions, the purpose of this study was to investigate disability resource professionals' perceptions of the influence of their identities and experiences in accommodation-related decision-making. Using a qualitative approach, researchers engaged in semi-structured interviews with a total of 13 disability resource professionals across the United States. Participants described identities and experiences as influential in their work, discussed the impact of holding both convergent and divergent identities with students, and shared strategies in response to the influence of these identities and experiences. The authors conclude with implications for the disability resources field as well as directions for future research.

To replace the current professional paradigm of higher education disability resources, socially-just disability resources emerged as the next step for the field to progress relative to creating experiences for students with disabilities that are not only accessible and equitable but also socially-just. Overall, descriptions of socially-just disability resources take the social model approach a step further by directly mobilizing disability resource professionals to organize for greater change in higher education to holistically address barriers with an ideal outcome of reducing the need for accommodations altogether. However, because this is a novel framework, there is a paucity of research regarding its implementation. The purpose of this study was to understand what the ideal implementation of socially just disability resources would entail and how these practices can be sustained. Following a review of the findings from an appreciative inquiry initiative conducted with one disability resource center, implications are discussed.

The mitogen-activated protein kinase (MAPK) p38 is an essential family of kinases, regulating responses to environmental stress and inflammation. There is an ever-increasing plethora of physiological and pathophysiological conditions attributed to p38 activity, ranging from cell division and embryonic development to the control of a multitude of diseases including retinal, cardiovascular, and neurodegenerative diseases, diabetes, and cancer. Despite the decades of intense investigation, a viable therapeutic approach to disrupt p38 signaling remains elusive. A growing body of evidence supports the pathological significance of an understudied atypical p38 signaling pathway. Atypical p38 signaling is driven by a direct interaction between the adaptor protein TAB1 and p38α, driving p38 autophosphorylation independent from the classical MKK3 and MKK6 pathways. Unlike the classical MKK3/6 signaling pathway, atypical signaling is selective for just p38α, and at present has only been characterized during pathophysiological stimulation. Recent studies have linked atypical signaling to dermal and vascular inflammation, myocardial ischemia, cancer metastasis, diabetes, complications during pregnancy, and bacterial and viral infections. Additional studies are required to fully understand how, when, where, and why atypical p38 signaling is induced. Furthermore, the development of selective TAB1-p38 inhibitors represents an exciting new opportunity to selectively inhibit pathological p38 signaling in a wide array of diseases.

Student engagement is a growing challenge within higher education, especially as technology continues to evolve and competition for attention rises. As a business discipline, many marketing students struggle to connect with the theory presented in the classroom and seek interactive, experiential learning opportunities. The authors created the "Find the Marketing in the Music" playlist matching activity to address this challenge and provide students with an engaging application of marketing concepts. Music is a means of personal expression and broadens listeners' perspectives. Music can help ignite or explain feelings, highlight complexities of social situations, and serve as a vehicle driving understanding and compassion. This featured activity reveals that by pairing songs that illustrate marketing concepts with information discussed in class, students could connect to the material in a new way. This exercise allows students to leverage the creative and grounded aspects of critical thinking by connecting something artistic with concrete marketing concepts. Students note that this activity helps them better relate to the material and that the relevancy of things discussed in the classroom takes on a new level when integrated into their everyday lives.

School-based service providers must understand how to best measure academic skill development given its key role in improving long-term outcomes for individuals with autism spectrum disorder (ASD). Curriculum-based measurement (CBM), which has applications for foundational academic skill areas of reading, writing, and mathematics, may be one way to determine academic intervention targets and progress monitor academic skills for students with ASD, but the extent of the literature base is unknown. Results of this scoping review regarding use of CBM with autistic students indicated few studies, overall. Studies had a wide range of sample sizes and primarily focused on intervention, using CBM as progress or outcome measures. Numerous demographic characteristics and study elements were absent from the literature. Future directions for this area of research and the implications for assessment in response to instruction for students with ASD are presented.

Men who have sex with men (MSM) in Vietnam experience disproportionate rates of HIV infection. To advance understanding of how structural barriers may shape their engagement with HIV prevention services, we draw on 32 in-depth interviews and four focus groups (n = 31) conducted with MSM in Hanoi between October 2015- March 2016. Three primary factors emerged: (1) Diversity, both in relation to identity and income; Vietnamese MSM described themselves as segregated into Bóng kín (hidden, often heterosexually-identified MSM) and Bóng lộ ('out,' transgender, or effeminate MSM). Lower-income, 'hidden' MSM from rural areas were reluctant to access MSM-targeted services; (2) Stigma: MSM reported being stigmatized by the healthcare system, family, and other MSM; and (3) Healthcare access: this was limited due to economic barriers and lack of MSM-friendly services. Our research suggests the need for multiple strategies to reach diverse types of MSM as well as to address barriers in access to health services such as stigma and costs. While a great deal has been written about the diversity of MSM in relation to gender performance and sexual identities, our research points to the substantial structural-level barriers that must be addressed in order to achieve meaningful and effective HIV prevention for MSM worldwide.

Familiarity between conspecifics may influence how social affective cues shape social behaviors. In a social affective preference test, experimental rats, when given the choice to explore an unfamiliar stressed or a naive adult, will avoid interaction with a stressed conspecific. To determine if familiarity would influence social interactions with stressed conspecifics, male and female test rats underwent 2 social affective preference tests in isosexual triads where an experimental rat was presented with a naïve and a stressed target conspecific who were either familiar (cagemate) or unfamiliar. Male and female experimental rats avoided stressed unfamiliar conspecifics. However, experimental female rats demonstrated a preference to interact with their stressed, familiar cagemates. Male and female rats exhibited more self-grooming and immobility behavior in the presence of stressed conspecifics, which may indicate emotion contagion. These findings suggest a sex-specific role of familiarity in social approach and avoidance, and warrant further mechanistic exploration.

Diamond-based low-work function thermionic electron emitters are in high demand for applications ranging from electron guns and space thrusters to electrical energy converters. A key requirement of such diamond-based electron sources is hydrogen termination of the surfaces which can significantly reduce the emission barrier. However, at high temperatures (≤600°C), terminated hydrogen begins to desorb causing degradation in thermionic emission performance. The purpose of this study is to examine low-pressure hydrogen operating environments as a means to overcome this high-temperature performance limitation by enabling increased thermionic emission currents with improved stability at temperatures ≤600°C. A series of isothermal and isobaric experiments were performed in both nitrogen and hydrogen gas environments to determine the performance enhancement. Diamond electron emitters in both the as-grown and hydrogenated states were characterized at temperatures of 600, 625, and 650°C. An increase in thermionic emission current over vacuum operation was observed following the introduction of hydrogen. Upon evacuation of hydrogen to vacuum, the emission current decreased back to baseline levels. Further experiments in gas environments at a constant pressure (~5.5 × 10−6 Torr) were conducted at temperatures ranging from 700 to 900°C. It was observed that the hydrogen environment promoted increased emission current while also enabling the diamond electron emitters to stably emit at increased temperatures compared with vacuum operation. Analogous experiments using nitrogen environments did not show any measurable performance enhancements, thus verifying that hydrogen is responsible for the observed effect. These results suggest diamond-based electron emitters can have improved thermionic emission performance at temperatures ≤600°C when operating in hydrogen gas environments.

We have developed an electrical-biological hybrid system wherein an engineered microorganism consumes electrocatalytically produced formate from CO2 to supplement the bioproduction of isobutanol, a valuable fuel chemical. Biological CO2 sequestration is notoriously slow compared to electrochemical CO2 reduction, while electrochemical methods struggle to generate carbon-carbon bonds which readily form in biological systems. A hybrid system provides a promising method for combining the benefits of both biology and electrochemistry. Previously, Escherichia coli was engineered to assimilate formate and CO2 in central metabolism using the reductive glycine pathway. In this work, we have shown that chemical production in E. coli can benefit from single carbon substrates when equipped with the RGP. By installing the RGP and the isobutanol biosynthetic pathway into E. coli and by further genetic modifications, we have generated a strain of E. coli that can consume formate and produce isobutanol at a yield of >100% of theoretical maximum from glucose. Our results demonstrate that carbon produced from electrocatalytically reduced CO2 can bolster chemical production in E. coli. This study shows that E. coli can be engineered towards carbon efficient methods of chemical production.