Vertical Distribution of Rocky Intertidal Organisms Shifts With Sea-Level Variability on the Northeast Pacific Coast.

Disentangling the effects of cyclical variability in environmental forcing and long-term climate change on natural communities is a major challenge for ecologists, managers, and policy makers across ecosystems. Here we examined whether the vertical distribution of rocky intertidal taxa has shifted with sea-level variability occurring at multiple temporal scales and/or long-term anthropogenic sea-level rise (SLR). Because of the distinct zonation characteristic of intertidal communities, any shift in tidal dynamics or average sea level is expected to have large impacts on community structure and function.

Wave damping by giant kelp, Macrocystis pyrifera.

Background And Aims: The increased likelihood and severity of storm events has brought into focus the role of coastal ecosystems in provision of shoreline protection by attenuating wave energy. Canopy-forming kelps, including giant kelp (Macrocystis pyrifera), are thought to provide this ecosystem service, but supporting data are extremely limited. Previous in situ examinations relied mostly on comparisons between nominally similar sites with and without kelp.

A bendable biological ceramic.

A fatigue-resistant mollusk hinge could in spire the development of new materials.

Quality by Design (QbD) Approach for a Nanoparticulate Imiquimod Formulation as an Investigational Medicinal Product.

The present article exemplifies the application of the concept of quality by design (QbD) for the systematic development of a nanoparticulate imiquimod (IMQ) emulsion gel formulation as an investigational medicinal product (IMP) for evaluation in an academic phase-I/II clinical trial for the treatment of actinic keratosis (AK) against the comparator Aldara (EudraCT: 2015-002203-28). The design of the QbD elements of a quality target product profile (QTPP) enables the identification of the critical quality attributes (CQAs) of the drug product as the content of IMQ, the particle-size distribution, the pH, the rheological properties, the permeation rate and the chemical, physical and microbiological stability. Critical material attributes (CMAs) and critical process parameters (CPPs) are identified by using a risk-based approach in an Ishikawa diagram and in a risk-estimation matrix.

Elevated Salinity Rapidly Confers Cross-Tolerance to High Temperature in a Splash-Pool Copepod.

Accurate forecasting of organismal responses to climate change requires a deep mechanistic understanding of how physiology responds to present-day variation in the physical environment. However, the road to physiological enlightenment is fraught with complications: predictable environmental fluctuations of any single factor are often accompanied by substantial stochastic variation and rare extreme events, and several factors may interact to affect physiology. Lacking sufficient knowledge of temporal patterns of co-variation in multiple environmental stressors, biologists struggle to design and implement realistic and relevant laboratory experiments.

Effects of heat acclimation on cardiac function in the intertidal mussel Mytilus californianus: can laboratory-based indices predict survival in the field?

Thermal performance curves are commonly used to investigate the effects of heat acclimation on thermal tolerance and physiological performance. However, recent work indicates that the metrics of these curves heavily depend on experimental design and may be poor predictors of animal survival during heat events in the field. In intertidal mussels, cardiac thermal performance (CTP) tests have been widely used as indicators of animals' acclimation or acclimatization state, providing two indices of thermal responses: critical temperature (Tcrit; the temperature above which heart rate abruptly declines) and flatline temperature (Tflat; the temperature where heart rate ceases).

The limits of convergence in the collective behavior of competing marine taxa.

Collective behaviors in biological systems such as coordinated movements have important ecological and evolutionary consequences. While many studies examine within-species variation in collective behavior, explicit comparisons between functionally similar species from different taxonomic groups are rare. Therefore, a fundamental question remains: how do collective behaviors compare between taxa with morphological and physiological convergence, and how might this relate to functional ecology and niche partitioning? We examined the collective motion of two ecologically similar species from unrelated clades that have competed for pelagic predatory niches for over 500 million years-California market squid, (Mollusca) and Pacific sardine, (Chordata).

Rapid Range Expansion of a Marine Ectotherm Reveals the Demographic and Ecological Consequences of Short-Term Variability in Seawater Temperature and Dissolved Oxygen.

AbstractThe distributions of marine ectotherms are governed by physiological sensitivities to long-term trends in seawater temperature and dissolved oxygen. Short-term variability in these parameters has the potential to facilitate rapid range expansions, and the resulting ecological and socioeconomic consequences may portend those of future marine communities. Here, we combine physiological experiments with ecological and demographic surveys to assess the causes and consequences of sudden but temporary poleward range expansions of a marine ectotherm with considerable life history plasticity (California market squid, ).

Physiological Consequences of Oceanic Environmental Variation: Life from a Pelagic Organism's Perspective.

To better understand life in the sea, marine scientists must first quantify how individual organisms experience their environment, and then describe how organismal performance depends on that experience. In this review, we first explore marine environmental variation from the perspective of pelagic organisms, the most abundant life forms in the ocean. Generation time, the ability to move relative to the surrounding water (even slowly), and the presence of environmental gradients at all spatial scales play dominant roles in determining the variation experienced by individuals, but this variation remains difficult to quantify.

Lung Deposition Using the Respimat Soft Mist™ Inhaler Mono and Fixed-Dose Combination Therapies: An / Analysis.

Tiotropium and olodaterol are mainstay treatments for chronic obstructive pulmonary disease (COPD) and yield important clinical improvements, especially when used in fixed-dose combination. Whilst previous studies have shown consistent delivery of tiotropium to the lungs with the Respimat inhaler, no such study has been carried out for olodaterol or the components of their fixed-dose combination (TIO/OLO). Combining and models, we measured the amount of drug retained in the mouth-throat area, entering the trachea and reaching the lung periphery.

A single heat-stress bout induces rapid and prolonged heat acclimation in the California mussel, .

Climate change is not only causing steady increases in average global temperatures but also increasing the frequency with which extreme heating events occur. These extreme events may be pivotal in determining the ability of organisms to persist in their current habitats. Thus, it is important to understand how quickly an organism's heat tolerance can be gained and lost relative to the frequency with which extreme heating events occur in the field.

Mussel acclimatization to high, variable temperatures is lost slowly upon transfer to benign conditions.

Climate change is increasing the temperature variability animals face, and thermal acclimatization allows animals to adjust adaptively to this variability. Although the rate of heat acclimatization has received some study, little is known about how long these adaptive changes remain without continuing exposure to heat stress. This study explored the rate at which field acclimatization states are lost when temperature variability is minimized during constant submersion.

Establishing typical values for hemocyte mortality in individual California mussels, Mytilus californianus.

Hemocytes are immune cells in the hemolymph of invertebrates that play multiple roles in response to stressors; hemocyte mortality can thus serve as an indicator of overall animal health. However, previous research has often analyzed hemolymph samples pooled from several individuals, which precludes tracking individual responses to stressors over time. The ability to track individuals is important, however, because large inter-individual variation in response to stressors can confound the interpretation of pooled samples.

A series of unfortunate events: characterizing the contingent nature of physiological extremes using long-term environmental records.

Accelerating shifts in global climate have focused the attention of ecologists and physiologists on extreme environmental events. However, the dynamic process of physiological acclimatization complicates study of these events' consequences. Depending on the range of plasticity and the amplitude and speed of environmental variation, physiology can be either in tune with the surroundings or dangerously out of synch.

Performance in a variable world: using Jensen's inequality to scale up from individuals to populations.

Body temperature affects plants' and animals' performance, but these effects are complicated by thermal variation through time within an individual and variation through space among individuals in a population. This review and synthesis describes how the effects of thermal variation-in both time and space-can be estimated by applying a simple, nonlinear averaging scheme. The method is first applied to the temporal variation experienced by an individual, providing an estimate of the individual's average performance.

Impact of heating rate on cardiac thermal tolerance in the California mussel, .

Intertidal communities of wave-swept rocky shores have served as a powerful model system for experiments in ecology, and mussels (the dominant competitor for space in the mid-intertidal zone) play a central role in determining community structure in this physically stressful habitat. Consequently, the ability to account for mussels' physiological responses to thermal stress affects ecologists' capacity to predict the impacts of a warming climate on this ecosystem. Here, we examined the effect of heating rate on cardiac thermal tolerance in the ribbed mussel, , comparing populations from high and low sites in the intertidal zone where emersion duration leads to different mean daily heating rates.

Transcutaneous immunization with CD40 ligation boosts cytotoxic T lymphocyte mediated antitumor immunity independent of CD4 helper cells in mice.

Transcutaneous immunization (TCI) is a novel vaccination strategy that utilizes skin-associated lymphatic tissue to induce immune responses. Employing T-cell epitopes and the TLR7 agonist imiquimod onto intact skin mounts strong primary, but limited memory CTL responses. To overcome this limitation, we developed a novel imiquimod-containing vaccination platform (IMI-Sol) rendering superior primary CD8 and CD4 T-cell responses.

Survival in spatially variable thermal environments: Consequences of induced thermal defense.

As Earth's climate warms, plants and animals are likely to encounter increased frequency and severity of extreme thermal events, and the ensuing destruction is likely to play an important role in structuring ecological communities. However, accurate prediction of the population-scale consequences of extreme thermal events requires detailed knowledge of the small-scale interaction between individual organisms and their thermal environment. In this study I propose a simple model that allows one to explore how individual-to-individual variation in body temperature and thermal physiology determines what fraction of a population will be killed by an extreme thermal event.

Combined immunotherapy: CTLA-4 blockade potentiates anti-tumor response induced by transcutaneous immunization.

Background: The epidermal application of the Toll Like Receptor 7 agonist imiquimod and a T-cell peptide epitope (transcutaneous immunization, TCI) mediates systemic peptide-specific cytotoxic T-cell (CTL) responses and leads to tumor protection in a prophylactic tumor setting. However, it does not accomplish memory formation or permanent defiance of tumors in a therapeutic set-up. As a distinct immunologic approach, CTLA-4 blockade augments systemic immune responses and has shown long-lasting effects in preclinical experiments as well as in clinical trials.

Transcutaneous immunization with a novel imiquimod nanoemulsion induces superior T cell responses and virus protection.

Background: Transcutaneous immunization (TCI) is a novel vaccination strategy utilizing the skin associated lymphatic tissue to induce immune responses. TCI using a cytotoxic T lymphocyte (CTL) epitope and the Toll-like receptor 7 (TLR7) agonist imiquimod mounts strong CTL responses by activation and maturation of skin-derived dendritic cells (DCs) and their migration to lymph nodes. However, TCI based on the commercial formulation Aldara only induces transient CTL responses that needs further improvement for the induction of durable therapeutic immune responses.

Coral larvae are poor swimmers and require fine-scale reef structure to settle.

Reef coral assemblages are highly dynamic and subject to repeated disturbances, which are predicted to increase in response to climate change. Consequently there is an urgent need to improve our understanding of the mechanisms underlying different recovery scenarios. Recent work has demonstrated that reef structural complexity can facilitate coral recovery, but the mechanism remains unclear.

The fallacy of the average: on the ubiquity, utility and continuing novelty of Jensen's inequality.

Biologists often cope with variation in physiological, environmental and ecological processes by measuring how living systems perform under average conditions. However, performance at average conditions is seldom equal to average performance across a range of conditions. This basic property of nonlinear averaging - known as 'Jensen's inequality' or 'the fallacy of the average' - has important implications for all of biology.

Long-term, high frequency in situ measurements of intertidal mussel bed temperatures using biomimetic sensors.

At a proximal level, the physiological impacts of global climate change on ectothermic organisms are manifest as changes in body temperatures. Especially for plants and animals exposed to direct solar radiation, body temperatures can be substantially different from air temperatures. We deployed biomimetic sensors that approximate the thermal characteristics of intertidal mussels at 71 sites worldwide, from 1998-present.

The extraordinary joint material of an articulated coralline alga. II. Modeling the structural basis of its mechanical properties.

By incorporating joints into their otherwise rigid fronds, erect coralline algae have evolved to be as flexible as other seaweeds, which allows them to thrive - and even dominate space - on wave-washed shores around the globe. However, to provide the required flexibility, the joint tissue of Calliarthron cheilosporioides, a representative articulated coralline alga, relies on an extraordinary tissue that is stronger, more extensible and more fatigue resistant than that of other algae. Here, we used the results from recent experiments to parameterize a conceptual model that links the microscale architecture of cell walls to the adaptive mechanical properties of joint tissue.