High concentrations of floating neustonic life in the plastic-rich North Pacific Garbage Patch.

Floating life (obligate neuston) is a core component of the ocean surface food web. However, only 1 region of high neustonic abundance is known so far, the Sargasso Sea in the Subtropical North Atlantic gyre, where floating life provides critical habitat structure and ecosystem services. Here, we hypothesize that floating life is also concentrated in other gyres with converging surface currents. To test this hypothesis, we collected samples through the eastern North Pacific Subtropical Gyre in the area of the North Pacific "Garbage Patch" (NPGP) known to accumulate floating anthropogenic debris. We found that densities of floating life were higher inside the central NPGP than on its periphery and that there was a positive relationship between neuston abundance and plastic abundance for 3 out of 5 neuston taxa, Velella, Porpita, and Janthina. This work has implications for the ecology of subtropical oceanic gyre ecosystems.

Responses of intraspecific metabolic scaling to temperature and activity differ between water- and air-breathing ectothermic vertebrates.

Metabolism underpins all life-sustaining processes and varies profoundly with body size, temperature and locomotor activity. A current theory explains some of the size-dependence of metabolic rate (its mass exponent, b) through changes in metabolic level (L). We propose two predictive advances that: (a) combine the above theory with the evolved avoidance of oxygen limitation in water-breathers experiencing warming, and (b) quantify the overall magnitude of combined temperatures and degrees of locomotion on metabolic scaling across air- and water-breathers. We use intraspecific metabolic scaling responses to temperature (523 regressions) and activity (281 regressions) in diverse ectothermic vertebrates (fish, reptiles and amphibians) to show that b decreases with temperature-increased L in water-breathers, supporting surface area-related avoidance of oxygen limitation, whereas b increases with activity-increased L in air-breathers, following volume-related influences. This new theoretical integration quantitatively incorporates different influences (warming, locomotion) and respiration modes (aquatic, terrestrial) on animal energetics.

Disrupting HIV-1 capsid formation causes cGAS sensing of viral DNA.

Detection of viral DNA by cyclic GMP-AMP synthase (cGAS) is a first line of defence leading to the production of type I interferon (IFN). As HIV-1 replication is not a strong inducer of IFN, we hypothesised that an intact capsid physically cloaks viral DNA from cGAS. To test this, we generated defective viral particles by treatment with HIV-1 protease inhibitors or by genetic manipulation of gag. These viruses had defective Gag cleavage, reduced infectivity and diminished capacity to saturate TRIM5α. Importantly, unlike wild-type HIV-1, infection with cleavage defective HIV-1 triggered an IFN response in THP-1 cells that was dependent on viral DNA and cGAS. An IFN response was also observed in primary human macrophages infected with cleavage defective viruses. Infection in the presence of the capsid destabilising small molecule PF-74 also induced a cGAS-dependent IFN response. These data demonstrate a protective role for capsid and suggest that antiviral activity of capsid- and protease-targeting antivirals may benefit from enhanced innate and adaptive immunity in vivo.

The impact of the COVID-19 lockdowns on wildlife-vehicle collisions in the UK.

Wildlife-vehicle collisions (WVCs) cause millions of vertebrate mortalities globally, threatening population viability and influencing wildlife behaviour and survival. Traffic volume and speed can influence wildlife mortality on roads, but roadkill risk is species specific and depends on ecological traits. The COVID-19 pandemic, and associated UK-wide lockdowns, offered a unique opportunity to investigate how reducing traffic volume alters WVC. These periods of reduced human mobility have been coined the 'anthropause'. We used the anthropause to identify which ecological traits may render species vulnerable to WVC. We did this by comparing the relative change in WVC of species with differing traits before and during the anthropause. We used Generalised Additive Model predictions to assess which of the 19 species most frequently observed as WVC in the UK exhibited changes in road mortality during two lockdown periods, March-May 2020 and December 2020-March 2021, relative to the same time periods in previous years (2014-2019). Compositional data analysis was used to identify ecological traits associated with changes in the relative number of observations during lockdown periods compared to previous years. WVC were, across all species, 80% lower during the anthropause than predicted. Compositional data analysis revealed proportionally fewer reports of nocturnal mammals, urban visitors, mammals with greater brain mass and birds with a longer flight initiation distance. Species that have several of these traits, and correspondingly significantly lower than predicted WVC during lockdowns, included badgers Meles meles, foxes Vulpes vulpes, and pheasants, Phasianus colchicus; we posit they stand to benefit most from reduced traffic, and, of the species studied here, have highest mortality under 'normal' traffic levels. This study identifies traits and species that may have experienced a temporary reprieve during the anthropause, and highlights the impacts of traffic-induced mortality on species numbers and ultimately on trait frequency in a road-dominated landscape. By taking advantage of reductions in traffic offered by the anthropause, we can understand how vehicles influence wildlife survival and behaviour and may be exerting a selective force for certain species and traits.

Undergraduate college students' awareness and perception of nature - a photovoice study.

BACKGROUND: There has been limited research on college campus' green spaces and their benefits to students. This study aimed to identify relationships between a Texas campus's green spaces and students' knowledge of their health benefits and their perception of their health compared to the campus' indoor built environments. METHODS: Photovoice was utilized to answer this study's research questions. Participants were instructed to take a photograph inside a building on campus and one outdoors anywhere on campus. Participants answered a questionnaire containing health-related questions, demographics, and nature relationship questions. Additionally, there was an in-class analysis and discussion to characterize overarching themes, knowledge, and evoked emotions. Frequencies, percentages, and a paired t-test were utilized to investigate the hypothesis that through the application of photovoice, participants would display more knowledge of nature's health benefits and a better perception of areas providing emotional, mental, physical, and social health benefits when in these green spaces compared to the indoor built environments on campus. RESULTS: 122 students took photographs and answered the questionnaire. 91 students participated in the in-class discussion. Most students felt more positive (80%) and perceived better health with their outdoor location compared to their indoor. They also responded higher to having more positive overall health benefits (63%) outdoors than indoors. CONCLUSIONS: These findings further solidified nature improves overall mood, there is a positive relationship between health and nature, and people are aware of it. Future studies should attempt to identify barriers accessing campus green spaces and develop interventions to encourage students to utilize these spaces.

Group-based trajectory analysis identifies varying diabetes-related cost trajectories among type 2 diabetes patients in Texas: an empirical study using commercial insurance.

BACKGROUND: The trend of Type 2 diabetes-related costs over 4 years could be classified into different groups. Patient demographics, clinical factors (e.g., A1C, short- and long-term complications), and rurality could be associated with different trends of cost. Study objectives are to: (1) understand the trajectories of cost in different groups; (2) investigate the relationship between cost and key factors in each cost trajectory group; and (3) assess significant factors associated with different cost trajectories. METHODS: Commercial claims data in Texas from 2016 to 2019 were provided by a large commercial insurer and were analyzed using group-based trajectory analysis, longitudinal analysis of cost, and logistic regression analyses of different trends of cost. RESULTS: Five groups of distinct trends of Type 2 diabetes-related cost were identified. Close to 20% of patients had an increasing cost trend over the 4 years. High A1C values, diabetes complications, and other comorbidities were significantly associated with higher Type 2 diabetes costs and higher chances of increasing trend over time. Rurality was significantly associated with higher chances of increasing trend over time. CONCLUSIONS: Group-based trajectory analysis revealed distinct patient groups with increased cost and stable cost at low, medium, and high levels in the 4-year period. The significant associations found between the trend of cost and A1C, complications, and rurality have important policy and program implications for potentially improving health outcomes and constraining healthcare costs.

High-affinity oligoclonal TCRs define effective adoptive T cell therapy targeting mutant KRAS-G12D.

Complete cancer regression occurs in a subset of patients following adoptive T cell therapy (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs). However, the low success rate presents a great challenge to broader clinical application. To provide insight into TIL-based immunotherapy, we studied a successful case of ACT where regression was observed against tumors carrying the hotspot mutation G12D in the KRAS oncogene. Four T cell receptors (TCRs) made up the TIL infusion and recognized two KRAS-G12D neoantigens, a nonamer and a decamer, all restricted by human leukocyte antigen (HLA) C*08:02. Three of them (TCR9a, 9b, and 9c) were nonamer-specific, while one was decamer-specific (TCR10). We show that only mutant G12D but not the wild-type peptides stabilized HLA-C*08:02 due to the formation of a critical anchor salt bridge to HLA-C. Therapeutic TCRs exhibited high affinities, ranging from nanomolar to low micromolar. Intriguingly, TCR binding affinities to HLA-C inversely correlated with their persistence in vivo, suggesting the importance of antigenic affinity in the function of therapeutic T cells. Crystal structures of TCR-HLA-C complexes revealed that TCR9a to 9c recognized G12D nonamer with multiple conserved contacts through shared CDR2ß and CDR3α. This allowed CDR3ß variation to confer different affinities via a variable HLA-C contact, generating an oligoclonal response. TCR10 recognized an induced and distinct G12D decamer conformation. Thus, this successful case of ACT included oligoclonal TCRs of high affinity recognizing distinct conformations of neoantigens. Our study revealed the potential of a structural approach to inform clinical efforts in targeting KRAS-G12D tumors by immunotherapy and has general implications for T cell-based immunotherapies.

Developing a secretory AcGFP1-based IRES expression system for efficient production of mammalian recombinant proteins.

To generate stable cell lines that express high levels of recombinant genes often requires screening of a large number of transfected cells using ELISA. The most widely used alternative to ELISA screening is to use an intracellularly expressed GFP reporter construct which allows sorting of recombinant gene expression cells based on GFP fluorescence intensity. The disadvantage of cell sorting, however, is that the resulting population will be polyclonal with the danger of instability and overgrowth of low producers. In addition, GFP or its variants can be toxic to host cells at high concentrations, and thus may reduce growth and robustness of high producer cells or even cause them to become apoptotic. We have developed a new mammalian expression system in which a recombinant protein and a fluorescence protein, AcGFP1, are expressed on the same plasmid separated by an internal ribosome entry site (IRES). A signal peptide was incorporated upstream of AcGFP1 so that the fluorescent protein is secreted from cells, preventing cellular toxicity from intracellular accumulation and enabling convenient and accurate measurement of the protein. Expression tests of Ebola viral envelope GP1 and HIV gp120 proteins using this expression system in 293-H cells showed recombinant protein expression levels were closely correlated with AcGFP1 yield. Therefore, AcGFP1 can serve as an accurate reporter for recombinant protein expression and measuring AcGFP1 concentration provides a convenient, product independent and universal way for efficient clone screening.

Muscular heat shock protein response and muscle damage after semi-professional football match.

PURPOSE: A typical football match leads to neuromuscular fatigue and physical performance impairments up to 72-96 h post-match. While muscle damage is thought to be a major factor, damage on the ultrastructural level has never been documented. The purpose of this study was to investigate post-match cellular muscle damage by quantifying the heat shock protein (HSP) response as a proxy for protein damage. METHODS: Muscle biopsies, blood samples, countermovement jumps, and perception of muscle soreness were obtained from twelve semi-professional football players 1, 24, 48, and 72 h after a 90-min football match. Muscle biopsies were analyzed for αB-crystallin and HSP70 in the cytosolic and cytoskeletal sub-cellular fractions by Western blotting. Fiber type-specific αB-crystallin and HSP70 staining intensity, and tenascin-C immunoreactivity were analyzed with immunohistochemistry. Blood samples were analyzed for creatine kinase and myoglobin. RESULTS: Within 24 h post-match, a 2.7- and 9.9-fold increase in creatine kinase and myoglobin were observed, countermovement jump performance decreased by -9.7% and muscle soreness increased by 0.68 units. αB-crystallin and HSP70 accumulated in cytoskeletal structures evident by a 3.6- and 1.8-fold increase in the cytoskeletal fraction and a parallel decrease in the cytosolic fraction. In type I and II fibers, αB-crystallin staining intensity increased by 15%-41% and remained elevated at 72 h post-match. Lastly, the percentage of fibers with granular staining of αB-crystallin increased 2.2-fold. CONCLUSIONS: Football match play induced a muscular HSP stress response 1-72 h post-match. Specifically, the accumulation of HSPs in cytoskeletal structures and the granular staining of αB-crystallin suggests occurrence of ultrastructural damage. The damage, indicated by the HSP response, might be one reason for the typically 72 h decrease in force-generating capacity after football matches.

Sea of bodies: a medical discourse of the refugee crisis in Tears of Salt: A Doctor's Story.

In the memoir Tears of Salt: A Doctor's Story, Pietro Bartolo (2018) relates visceral descriptions of illness, injury and death endured by refugees on their journey of escape to the shores of Lampedusa in the Mediterranean. The medical gaze of the doctor/author further complicates the political and philosophical discourse of mass migration, foregrounding and calling into question the myriad ways in which the migrating human body is subjugated to forms of structural violence that render it ungrievable and inhuman. The migrating body, a production of and outcast from nation-states, is destined to make its way to news outlets where its suffering is gazed upon, sympathised with and later forgotten about. The surge of images revealing the realities of migrating bodies afflicted with pain, disease, trauma and sexual assault is illustrative of the asymmetric power of biopolitics at work, in which some bodies are, according to the formulations of Judith Butler and Giorgio Agamben, allowed to die or made killable. This paper will examine issues of illness, death and dying in relation to Bartolo's accounts of refugees in order to observe what is gained and what is lost in applying a medical gaze to the 'refugee crisis'. In addition to the memoir, we examine the scholarship of violence against the refugee body, the realities of ignoring their pain and how these exploited bodies are portrayed within a global narrative. This article reconfigures the detachment between the human as a socially constructed centre of subjectivity and the body in pain. The corporeality of illness and death that migrants face positions them in an abject position and distances them farther from the rhetoric of human rights. The ontological being of these individuals in medical discourse rarely goes beyond acknowledging that it is normal and expected for these bodies to be in pain. In what ways can we in the humanities gear the discussion towards the raw physicality of fragmentation, distortion and rejection of refugees and immigrants? What role can such a view play in building an ethic of lasting care for the dispossessed? Our research addresses these questions through our reading of the memoir.

Aromatic Residues at the Dimer-Dimer Interface in the Peroxiredoxin Tsa1 Facilitate Decamer Formation and Biological Function.

To prevent the accumulation of reactive oxygen species and limit associated damage to biological macromolecules, cells express a variety of oxidant-detoxifying enzymes, including peroxiredoxins. In Saccharomyces cerevisiae, the peroxiredoxin Tsa1 plays a key role in peroxide clearance and maintenance of genome stability. Five homodimers of Tsa1 can assemble into a toroid-shaped decamer, with the active sites in the enzyme being shared between individual dimers in the decamer. Here, we have examined whether two conserved aromatic residues at the decamer-building interface promote Tsa1 oligomerization, enzymatic activity, and biological function. When substituting either or both of these aromatic residues at the decamer-building interface with either alanine or leucine, we found that the Tsa1 decamer is destabilized, favoring dimeric species instead. These proteins exhibit varying abilities to rescue the phenotypes of oxidant sensitivity and genomic instability in yeast lacking Tsa1 and Tsa2, with the individual leucine substitutions at this interface partially complementing the deletion phenotypes. The ability of Tsa1 decamer interface variants to partially rescue peroxidase function in deletion strains is temperature-dependent and correlates with their relative rate of reactivity with hydrogen peroxide and their ability to interact with thioredoxin. Based on the combined results of in vitro and in vivo assays, our findings indicate that multiple steps in the catalytic cycle of Tsa1 may be impaired by introducing substitutions at its decamer-building interface, suggesting a multifaceted biological basis for its assembly into decamers.

Over-expression of a human CD62L ecto-domain and a potential role of RNA pseudoknot structures in recombinant protein expression.

L-selectin (CD62L) is an extracellular protein with a lectin-like domain that mediates rolling adhesion of leukocytes to vascular endothelial cell surfaces. Currently, there are no solved structures for the ectodomain of CD62L, nor of CD62L in complex with its ligand. We have developed a rapid mammalian recombinant protein expression system using an amplifiable glutamine synthase based vector. Here, we further developed and applied this method to express and purify the entire extracellular region of CD62L. This resulted in excess of 20 mg/L yield of recombinant CD62L. In an attempt to understand the different expression levels among four similar CD62L constructs that differ primarily in signal sequences, we calculated the presence of potential RNA pseudoknots in their signal sequences. The results showed the presence of pseudoknots involving the start codon and between the signal sequence and gene in the mRNA of the non-expressing constructs, suggesting a potential inhibitory role of RNA pseudoknots in recombinant protein expression.

Does the National Resident Match Program Rank List Predict Success in Emergency Medicine Residency Programs?

BACKGROUND: Emergency medicine (EM) residency programs use nonstandardized criteria to create applicant rank lists. One implicit assumption is that predictive associations exist between an applicant's rank and their future performance as a resident. To date, these associations have not been sufficiently demonstrated. OBJECTIVES: We hypothesized that a strong positive correlation exists between the National Resident Match Program (NRMP) match-list applicant rank, the United States Medical Licensing Examination (USMLE) Step 1 and In-Training Examination (ITE) scores, and the graduating resident rank. METHODS: A total of 286 residents from five EM programs over a 5-year period were studied. The applicant rank (AR) was derived from the applicant's relative rank list position on each programs' submitted NRMP rank list. The graduation rank (GR) was determined by a faculty consensus committee. GR was then correlated to AR using a Spearman's partial rank correlation. Additional correlations were sought with a ranking of the USMLE Step Score (UR) and the ITE Score (IR). RESULTS: Combining data for all five programs, weak positive correlations existed between GR and AR, UR, and IR. The majority of correlations ranged between. When comparing GR and AR, there was a weak correlation of 0.13 (p = 0.03). CONCLUSION: Our study found only weak correlations between GR and AR, UR, and IR, suggesting that those variables may not be strong predictors of resident performance. This has important implications for EM programs considering the resources devoted to applicant evaluation and ranking.

Profiles of low complexity regions in Apicomplexa.

BACKGROUND: Low complexity regions (LCRs) are a ubiquitous feature in genomes and yet their evolutionary history and functional roles are unclear. Previous studies have shown contrasting evidence in favor of both neutral and selective mechanisms of evolution for different sets of LCRs suggesting that modes of identification of these regions may play a role in our ability to discern their evolutionary history. To further investigate this issue, we used a multiple threshold approach to identify species-specific profiles of proteome complexity and, by comparing properties of these sets, determine the influence that starting parameters have on evolutionary inferences. RESULTS: We find that, although qualitatively similar, quantitatively each species has a unique LCR profile which represents the frequency of these regions within each genome. Inferences based on these profiles are more accurate in comparative analyses of genome complexity as they allow to determine the relative complexity of multiple genomes as well as the type of repetitiveness that is most common in each. Based on the multiple threshold LCR sets obtained, we identified predominant evolutionary mechanisms at different complexity levels, which show neutral mechanisms acting on highly repetitive LCRs (e.g., homopolymers) and selective forces becoming more important as heterogeneity of the LCRs increases. CONCLUSIONS: Our results show how inferences based on LCRs are influenced by the parameters used to identify these regions. Sets of LCRs are heterogeneous aggregates of regions that include homo- and heteropolymers and, as such, evolve according to different mechanisms. LCR profiles provide a new way to investigate genome complexity across species and to determine the driving mechanism of their evolution.

Effectiveness of glucagon in relieving esophageal foreign body impaction: a multicenter study.

PURPOSE: Glucagon is thought to decrease lower esophageal sphincter tone and is used as an alternative to invasive endoscopy for esophageal foreign body impaction (EFBI). The purpose of this study was to evaluate efficacy and safety of glucagon and identify characteristics associated with success. METHODS: A multicenter, retrospective study of patients receiving glucagon for EFBI at 2 academic emergency departments was conducted between 2006 and 2010. A control group of patients that did not receive glucagon was evaluated. Data collection included demographics, type of foreign body, glucagon dose, resolution of impaction, incidence of vomiting, additional medication, and endoscopy required. Descriptive and univariate analysis was performed as appropriate. RESULTS: A total of 133 doses of glucagon were administered in 127 patients. Glucagon-related resolution of EFBI occurred in 18 patients (14.2%) and vomiting in 16 patients (12.6%). No statistical differences between successful and unsuccessful groups were seen with the exception of concomitant medication administration (benzodiazepine or nitroglycerin) being associated with less glucagon success, 33.3% vs 59.6%, respectively (P = .04). Eighty-four percent of patients in the unsuccessful group underwent endoscopy. Comparing those that received glucagon (n = 127) and the control group (n = 29), there was no significant difference in resolution of EFBI, 14.2% vs 10.3%, respectively (P = .586). CONCLUSIONS: Glucagon-related resolution occurred in 14.2% of patients and was not significantly different compared with those that did not receive glucagon (10.3%). Concomitant medication administration was associated with lower success. Overall, glucagon had a low success rate, was related to adverse effects, and does not offer advantages for treatment.

Stochastic dynamics of a warmer Great Barrier Reef.

Pressure on natural communities from human activities continues to increase. Even unique ecosystems like the Great Barrier Reef (GBR), that until recently were considered near-pristine and well-protected, are showing signs of rapid degradation. We collated recent (1996-2006) spatiotemporal relationships between benthic community composition on the GBR and environmental variables (ocean temperature and local threats resulting from human activity). We built multivariate models of the effects of these variables on short-term dynamics, and developed an analytical approach to study their long-term consequences. We used this approach to study the effects of ocean warming under different levels of local threat. Observed short-term changes in benthic community structure (e.g., declining coral cover) were associated with ocean temperature (warming) and local threats. Our model projected that, in the long-term, coral cover of less than 10% was not implausible. With increasing temperature and/or local threats, corals were initially replaced by sponges, gorgonians, and other taxa, with an eventual moderately high probability of domination (> 50%) by macroalgae when temperature increase was greatest (e.g., 3.5 degrees C of warming). Our approach to modeling community dynamics, based on multivariate statistical models, enabled us to project how environmental change (and thus local and international policy decisions) will influence the future state of coral reefs. The same approach could be applied to other systems for which time series of ecological and environmental variables are available.

Size change, shape change, and the growth space of a community.

Measures of biodiversity change such as the Living Planet Index describe proportional change in the abundance of a typical species, which can be thought of as change in the size of a community. Here, I discuss the orthogonal concept of change in relative abundances, which I refer to as shape change. To be logically consistent, a measure of the rate of shape change should be scaling invariant (have the same value for all data with the same vector of proportional change over a given time interval), but existing measures do not have this property. I derive a new, scaling invariant measure. I show that this new measure and existing measures of biodiversity change such as the Living Planet Index describe different aspects of dynamics. I show that neither body size nor environmental variability need affect the rate of shape change. I extend the measure to deal with colonizations and extinctions, using the surreal number system. I give examples using data on hoverflies in a garden in Leicester, UK, and the higher plant community of Surtsey. I hypothesize that phylogenetically restricted assemblages will show a higher proportion of size change than diverse communities.

The critical role of O2 provision in the dynamic adjustment of oxidative phosphorylation.

It has been proposed that the adjustment of oxygen uptake (V˙O2) during the exercise on-transient is controlled intracellularly in young healthy individuals and that insufficient local O2 delivery plays a rate-limiting role in aging and disease only. This review shows that adequate O2 provision to the active tissues is critical in the dynamic adjustment of oxidative phosphorylation even in young healthy individuals.

Collaboration and engagement with decision-makers are needed to reduce evidence complacency in wildlife management.

There exists an extensive, diverse, and robust evidence base to support complex decisions that address the planetary biodiversity crisis. However, it is generally not sought or used by environmental decision-makers, who instead draw on intuition, experience, or opinion to inform important decisions. Thus, there is a need to examine evidence exchange processes in wildlife management to understand the multiple inputs to decisions. Here, we adopt a novel approach, fuzzy cognitive mapping (FCM), to examine perceptions of individuals from Indigenous and Western governments on the reliability of evidence which may influence freshwater fisheries management decisions in British Columbia, Canada. We facilitated four FCM workshops participants representing Indigenous or Western regulatory/governance groups of fisheries managers. Our results show that flows of evidence to decision-makers occur within a relatively closed governance network, constrained to the few well-connected decision-making organizations (i.e., wildlife management agencies) and their close partners. This implies that increased collaboration (i.e., knowledge co-production) and engagement (i.e., knowledge brokerage) with wildlife managers and decision-makers are needed to produce actionable evidence and increase evidence exchange.