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.

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.

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 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.

Estimating the impact of new high seas activities on the environment: the effects of ocean-surface macroplastic removal on sea surface ecosystems.

The open ocean beyond national jurisdiction covers nearly half of Earth's surface and is largely unexplored. It is also an emerging frontier for new types of human activity. Understanding how new activities interact with high seas ecosystems is critical for our management of this other half of Earth. Using The Ocean Cleanup (TOC) as a model, we demonstrate why it is important to account for uncertainty when assessing and evaluating impacts of novel high seas activities on marine ecosystems. TOC's aim is to remove plastic from the ocean surface by collecting it with large nets. However, this approach also results in the collection of surface marine life (neuston) as by-catch. Using an interdisciplinary approach, we explore the social-ecological implications of this activity. We use population models to quantify potential impacts on the surface ecosystem; we determine the links between these ecosystems and society through an ecosystem services approach; and we review the governance setting relevant to the management of activities on the high seas. We show that the impact of ocean surface plastic removal largely depends on neuston life histories, and ranges from potentially mild to severe. We identify broader social-ecological implications that could be felt by stakeholders both beyond and within national jurisdiction. The legal framework applicable to TOC's activities is insufficiently specific to address both the ecological and social uncertainty we describe, demonstrating the urgent need for detailed rules and procedures on environmental impact assessment and strategic environmental assessment to be adopted under the new International Agreement on the conservation and sustainable use of marine biological diversity of areas beyond national jurisdiction which is currently being negotiated.

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.

Negative and positive interspecific interactions involving jellyfish polyps in marine sessile communities.

Sessile marine invertebrates on hard substrates are one of the two canonical examples of communities structured by competition, but some aspects of their dynamics remain poorly understood. Jellyfish polyps are an important but under-studied component of these communities. We determined how jellyfish polyps interact with their potential competitors in sessile marine hard-substrate communities, using a combination of experiments and modelling. We carried out an experimental study of the interaction between polyps of the moon jellyfish Aurelia aurita and potential competitors on settlement panels, in which we determined the effects of reduction in relative abundance of either A. aurita or potential competitors at two depths. We predicted that removal of potential competitors would result in a relative increase in A. aurita that would not depend on depth, and that removal of A. aurita would result in a relative increase in potential competitors that would be stronger at shallower depths, where oxygen is less likely to be limiting. Removal of potential competitors resulted in a relative increase in A. aurita at both depths, as predicted. Unexpectedly, removal of A. aurita resulted in a relative decrease in potential competitors at both depths. We investigated a range of models of competition for space, of which the most successful involved enhanced overgrowth of A. aurita by potential competitors, but none of these models was completely able to reproduce the observed pattern. Our results suggest that interspecific interactions in this canonical example of a competitive system are more complex than is generally believed.

FcγRI FG-loop functions as a pH sensitive switch for IgG binding and release.

Understanding the molecular mechanism underlying the hierarchic binding between FcγRs and IgG antibodies is critical for therapeutic antibody engineering and FcγR functions. The recent determination of crystal structures of FcγRI-Fc complexes, however, resulted in two controversial mechanisms for the high affinity receptor binding to IgG. Here, we describe high resolution structures of a bovine FG-loop variant of FcγRI in complex with the Fc fragment of IgG1 crystallized in three different conditions at neutral pH, confirming the characteristic FG loop-Fc interaction is critical to the high affinity immunoglobulin binding. We showed that the FcγRI D2-domain FG-loop functioned as a pH-sensing switch for IgG binding. Further live cell imaging of FcγRI-mediated internalization of immune complexes showed a pH sensitive temporal-spatial antibody-antigen uptake and release. Taken together, we demonstrate that the structures of FcγRI-Fc crystallized at neutral and acidic pH, respectively, represent the high and low affinity binding states of the receptor for IgG uptake and release. These results support a role for FcγRI in antigen delivery, highlight the importance of Fc glycan in antibody binding to the high affinity receptor and provide new insights to future antibody engineering.

A Normalized Model of a Microelectromechanical Relay Calibrated by Laser-Doppler Vibrometry.

This work presents a behavioral model for a microelectromechanical (MEM) relay for use in circuit simulation. Models require calibration, and other published relay models require over a dozen parameters for calibration, many of which are difficult to extract or are only available after finite element analysis. This model improves on prior work by taking advantage of model normalization, which often results in models that require fewer parameters than un-normalized models. This model only needs three parameters extracted from experiment and one dimension known from device fabrication to represent its non-contact behavior, and two additional extracted parameters to represent its behavior when in contact. The extracted parameters-quality factor, resonant frequency, and the pull-in voltage-can be found using laser Doppler vibrometry. The device dimension is the actuation gap size, which comes from process data. To demonstrate this extraction process, a series of velocity step responses were excited in MEM relays, the measured velocity responses were used to calibrate the model, and then then simulations of the model (implemented in Verilog-A) were compared against the measured data. The error in the simulated oscillation frequency and peak velocity, two values selected as figures of merit, is less than 10% across many operating voltages.

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.

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.

Dyspnea during exercise and voluntary hyperpnea in women with obesity.

Temporal responses of ratings of perceived breathlessness (RBP) during constant-load and incremental exercise, and during voluntary hyperpnea (EVH) were examined in women with obesity. Following 6 min of constant-load (60W) cycling, 34 women rated RPB≥4 (+DOE) and 22 women rated RPB≤2 (-DOE). Both groups completed an incremental cycling test and an EVH test at 40 and 60L/min; RPB was assessed each minute of incremental cycling and at the end of each EVH trial. RPB increased with ventilation during constant-load (+DOE: R2=0.86; -DOE: R2=0.82) and incremental (+DOE: R2=0.91; -DOE: R2=0.92) exercise, but + DOE had a greater y-intercept than -DOE (60W: -0.16±1.53 vs. -0.73±0.55; incremental: -0.50±1.40 vs. -1.71±0.84). Despite matching ventilation, RPB was greater in + DOE at baseline (0.97±1.14 vs. 0.14±0.28), 40L/min (2.50±1.43 vs. 0.98±0.91), and 60L/min (3.94±2.19 vs. 2.07±1.32) during EVH. These findings show that despite linear associations between RPB and ventilation during exercise and voluntary hyperpnea, breathlessness perception at a given ventilatory demand is heightened in +DOE compared with -DOE.

Generalized Linear Models outperform commonly used canonical analysis in estimating spatial structure of presence/absence data.

BACKGROUND: Ecological communities tend to be spatially structured due to environmental gradients and/or spatially contagious processes such as growth, dispersion and species interactions. Data transformation followed by usage of algorithms such as Redundancy Analysis (RDA) is a fairly common approach in studies searching for spatial structure in ecological communities, despite recent suggestions advocating the use of Generalized Linear Models (GLMs). Here, we compared the performance of GLMs and RDA in describing spatial structure in ecological community composition data. We simulated realistic presence/absence data typical of many ß-diversity studies. For model selection we used standard methods commonly used in most studies involving RDA and GLMs. METHODS: We simulated communities with known spatial structure, based on three real spatial community presence/absence datasets (one terrestrial, one marine and one freshwater). We used spatial eigenvectors as explanatory variables. We varied the number of non-zero coefficients of the spatial variables, and the spatial scales with which these coefficients were associated and then compared the performance of GLMs and RDA frameworks to correctly retrieve the spatial patterns contained in the simulated communities. We used two different methods for model selection, Forward Selection (FW) for RDA and the Akaike Information Criterion (AIC) for GLMs. The performance of each method was assessed by scoring overall accuracy as the proportion of variables whose inclusion/exclusion status was correct, and by distinguishing which kind of error was observed for each method. We also assessed whether errors in variable selection could affect the interpretation of spatial structure. RESULTS: Overall GLM with AIC-based model selection (GLM/AIC) performed better than RDA/FW in selecting spatial explanatory variables, although under some simulations the methods performed similarly. In general, RDA/FW performed unpredictably, often retaining too many explanatory variables and selecting variables associated with incorrect spatial scales. The spatial scale of the pattern had a negligible effect on GLM/AIC performance but consistently affected RDA's error rates under almost all scenarios. CONCLUSION: We encourage the use of GLM/AIC for studies searching for spatial drivers of species presence/absence patterns, since this framework outperformed RDA/FW in situations most likely to be found in natural communities. It is likely that such recommendations might extend to other types of explanatory variables.

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.

Anterior Cruciate Ligament Repair Using a Knotless Suture Implant.

Recent orthopedic literature has shown that primary repair for femoral-sided avulsion tears of the anterior cruciate ligament (ACL) can be successful. Primary ACL repair avoids invasive reconstruction techniques, graft-site morbidity, and the loss of native anatomy while producing excellent results in appropriately selected patients. Here we describe our patient selection parameters, ACL repair technique, and rehabilitation protocol.

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.