Physical science research needed to evaluate the viability and risks of marine cloud brightening.

Marine cloud brightening (MCB) is the deliberate injection of aerosol particles into shallow marine clouds to increase their reflection of solar radiation and reduce the amount of energy absorbed by the climate system. From the physical science perspective, the consensus of a broad international group of scientists is that the viability of MCB will ultimately depend on whether observations and models can robustly assess the scale-up of local-to-global brightening in today's climate and identify strategies that will ensure an equitable geographical distribution of the benefits and risks associated with projected regional changes in temperature and precipitation. To address the physical science knowledge gaps required to assess the societal implications of MCB, we propose a substantial and targeted program of research-field and laboratory experiments, monitoring, and numerical modeling across a range of scales.

Assessing effective radiative forcing from aerosol-cloud interactions over the global ocean.

How clouds respond to anthropogenic sulfate aerosols is one of the largest sources of uncertainty in the radiative forcing of climate over the industrial era. This uncertainty limits our ability to predict equilibrium climate sensitivity (ECS)-the equilibrium global warming following a doubling of atmospheric CO2. Here, we use satellite observations to quantify relationships between sulfate aerosols and low-level clouds while carefully controlling for meteorology. We then combine the relationships with estimates of the change in sulfate concentration since about 1850 to constrain the associated radiative forcing. We estimate that the cloud-mediated radiative forcing from anthropogenic sulfate aerosols is [Formula: see text] W m-2 over the global ocean (95% confidence). This constraint implies that ECS is likely between 2.9 and 4.5 K (66% confidence). Our results indicate that aerosol forcing is less uncertain and ECS is probably larger than the ranges proposed by recent climate assessments.

Opportunistic experiments to constrain aerosol effective radiative forcing.

Aerosol-cloud interactions (ACIs) are considered to be the most uncertain driver of present-day radiative forcing due to human activities. The nonlinearity of cloud-state changes to aerosol perturbations make it challenging to attribute causality in observed relationships of aerosol radiative forcing. Using correlations to infer causality can be challenging when meteorological variability also drives both aerosol and cloud changes independently. Natural and anthropogenic aerosol perturbations from well-defined sources provide "opportunistic experiments" (also known as natural experiments) to investigate ACI in cases where causality may be more confidently inferred. These perturbations cover a wide range of locations and spatiotemporal scales, including point sources such as volcanic eruptions or industrial sources, plumes from biomass burning or forest fires, and tracks from individual ships or shipping corridors. We review the different experimental conditions and conduct a synthesis of the available satellite datasets and field campaigns to place these opportunistic experiments on a common footing, facilitating new insights and a clearer understanding of key uncertainties in aerosol radiative forcing. Cloud albedo perturbations are strongly sensitive to background meteorological conditions. Strong liquid water path increases due to aerosol perturbations are largely ruled out by averaging across experiments. Opportunistic experiments have significantly improved process-level understanding of ACI, but it remains unclear how reliably the relationships found can be scaled to the global level, thus demonstrating a need for deeper investigation in order to improve assessments of aerosol radiative forcing and climate change.

The hemispheric contrast in cloud microphysical properties constrains aerosol forcing.

The change in planetary albedo due to aerosol-cloud interactions during the industrial era is the leading source of uncertainty in inferring Earth's climate sensitivity to increased greenhouse gases from the historical record. The variable that controls aerosol-cloud interactions in warm clouds is droplet number concentration. Global climate models demonstrate that the present-day hemispheric contrast in cloud droplet number concentration between the pristine Southern Hemisphere and the polluted Northern Hemisphere oceans can be used as a proxy for anthropogenically driven change in cloud droplet number concentration. Remotely sensed estimates constrain this change in droplet number concentration to be between 8 cm-3 and 24 cm-3 By extension, the radiative forcing since 1850 from aerosol-cloud interactions is constrained to be -1.2 W⋅m-2 to -0.6 W⋅m-2 The robustness of this constraint depends upon the assumption that pristine Southern Ocean droplet number concentration is a suitable proxy for preindustrial concentrations. Droplet number concentrations calculated from satellite data over the Southern Ocean are high in austral summer. Near Antarctica, they reach values typical of Northern Hemisphere polluted outflows. These concentrations are found to agree with several in situ datasets. In contrast, climate models show systematic underpredictions of cloud droplet number concentration across the Southern Ocean. Near Antarctica, where precipitation sinks of aerosol are small, the underestimation by climate models is particularly large. This motivates the need for detailed process studies of aerosol production and aerosol-cloud interactions in pristine environments. The hemispheric difference in satellite estimated cloud droplet number concentration implies preindustrial aerosol concentrations were higher than estimated by most models.

Remote Sensing of Droplet Number Concentration in Warm Clouds: A Review of the Current State of Knowledge and Perspectives.

The cloud droplet number concentration (N d) is of central interest to improve the understanding of cloud physics and for quantifying the effective radiative forcing by aerosol-cloud interactions. Current standard satellite retrievals do not operationally provide N d, but it can be inferred from retrievals of cloud optical depth (τ c) cloud droplet effective radius (r e) and cloud top temperature. This review summarizes issues with this approach and quantifies uncertainties. A total relative uncertainty of 78% is inferred for pixel-level retrievals for relatively homogeneous, optically thick and unobscured stratiform clouds with favorable viewing geometry. The uncertainty is even greater if these conditions are not met. For averages over 1° ×1° regions the uncertainty is reduced to 54% assuming random errors for instrument uncertainties. In contrast, the few evaluation studies against reference in situ observations suggest much better accuracy with little variability in the bias. More such studies are required for a better error characterization. N d uncertainty is dominated by errors in r e, and therefore, improvements in r e retrievals would greatly improve the quality of the N d retrievals. Recommendations are made for how this might be achieved. Some existing N d data sets are compared and discussed, and best practices for the use of N d data from current passive instruments (e.g., filtering criteria) are recommended. Emerging alternative N d estimates are also considered. First, new ideas to use additional information from existing and upcoming spaceborne instruments are discussed, and second, approaches using high-quality ground-based observations are examined.

Large-scale climatic effects on traditional Hawaiian fishpond aquaculture.

Aquaculture accounts for almost one-half of global fish consumption. Understanding the regional impact of climate fluctuations on aquaculture production thus is critical for the sustainability of this crucial food resource. The objective of this work was to understand the role of climate fluctuations and climate change in subtropical coastal estuarine environments within the context of aquaculture practices in He'eia Fishpond, O'ahu Island, Hawai'i. To the best of our knowledge, this was the first study of climate effects on traditional aquaculture systems in the Hawaiian Islands. Data from adjacent weather stations were analyzed together with in situ water quality instrument deployments spanning a 12-year period (November 2004 -November 2016). We found correlations between two periods with extremely high fish mortality at He'eia Fishpond (May and October 2009) and slackening trade winds in the week preceding each mortality event, as well as surface water temperatures elevated 2-3°C higher than the background periods (March-December 2009). We posit that the lack of trade wind-driven surface water mixing enhanced surface heating and stratification of the water column, leading to hypoxic conditions and stress on fish populations, which had limited ability to move within net pen enclosures. Elevated water temperature and interruption of trade winds previously have been linked to the onset of El Niño in Hawai'i. Our results provide empirical evidence regarding El Niño effects on the coastal ocean, which can inform resource management efforts about potential impact of climate variation on aquaculture production. Finally, we provide recommendations for reducing the impact of warming events on fishponds, as these events are predicted to increase in magnitude and frequency as a consequence of global warming.

Cellular permeation of large molecules mediated by TRPM8 channels.

While most membrane channels are only capable of passing small ions, certain non-selective cation channels have been recently shown to have the capacity to permeate large cations. The mechanisms underlying large molecule permeation are unclear, but this property has been exploited pharmacologically to target molecules, such as nerve conduction blockers, to specific subsets of pain-sensing neurons (nociceptors) expressing the heat-gated transient receptor potential (TRP) channel TRPV1. However, it is not clear if the principal mediator of cold stimuli TRPM8 is capable of mediating the permeation large molecules across cell membranes, suggesting that TRPM8-positive nerves cannot be similarly targeted. Here we show that both heterologous cells and native sensory neurons expressing TRPM8 channels allow the permeation of the large fluorescent cation Po-Pro3. Po-Pro3 influx is blocked by TRPM8-specific antagonism and when channel activity is desensitized. The effects of the potent agonist WS-12 are TRPM8-specific and dye uptake mediated by TRPM8 channels is similar to that observed with TRPV1. Lastly, we find that as with TRPV1, activation of TRPM8 channels can be used as a means to target intracellular uptake of cell-impermeable sodium channel blockers. In a neuronal cell line expressing TRPM8 channels, voltage-gated sodium currents are blocked in the presence of the cell-impermeable, charged lidocaine derivative QX-314 and WS-12. These results show that the ability of somatosensory TRP channels to promote the permeation of large cations also includes TRPM8, thereby suggesting that novel approaches to alter cold pain can also be employed via conduction block in TRPM8-positive sensory neurons.

Iterative Design and Usability Testing of the Imhere System for Managing Chronic Conditions and Disability.

A novel mobile health platform, Interactive Mobile Health and Rehabilitation (iMHere), is being developed to support wellness and self-management among people with chronic disabilities. The iMHere system currently includes a smartphone app with six modules for use by persons with disabilities and a web portal for use by medical and rehabilitation professionals or other support personnel. Our initial clinical research applying use of this system provides insight into the feasibility of employing iMHere in the development of self-management skills in young adults (ages 18-40 years) with spina bifida (SB) (Dicianno, Fairman, et al., 2015). This article describes the iterative design of the iMHere system including usability testing of both the app modules and clinician portal. Our pilot population of persons with SB fostered the creation of a system appropriate for people with a wide variety of functional abilities and needs. As a result, the system is appropriate for use by persons with various disabilities and chronic conditions, not only SB. In addition, the diversity of professionals and support personnel involved in the care of persons with SB also enabled the design and implementation of the iMHere system to meet the needs of an interdisciplinary team of providers who treat various conditions. The iMHere system has the potential to foster communication and collaboration among members of an interdisciplinary healthcare team, including individuals with chronic conditions and disabilities, for a client-centered approach to support self-management skills.

Dual activities of the anti-cancer drug candidate PBI-05204 provide neuroprotection in brain slice models for neurodegenerative diseases and stroke.

We previously reported neuroprotective activity of the botanical anti-cancer drug candidate PBI-05204, a supercritical CO2 extract of Nerium oleander, in brain slice and in vivo models of ischemic stroke. We showed that one component of this neuroprotective activity is mediated through its principal cardiac glycoside constituent, oleandrin, via induction of the potent neurotrophic factor brain-derived neurotrophic factor (BDNF). However, we also noted that the concentration-relation for PBI-05204 in the brain slice oxygen-glucose deprivation (OGD) model is considerably broader than that for oleandrin as a single agent. We thus surmised that PBI-05204 contains an additional neuroprotective component(s), distinct from oleandrin. We report here that neuroprotective activity is also provided by the triterpenoid constituents of PBI-05204, notably oleanolic acid. We demonstrate that a sub-fraction of PBI-05204 (Fraction 0-4) containing oleanolic and other triterpenoids, but without cardiac glycosides, induces the expression of cellular antioxidant gene transcription programs regulated through antioxidant transcriptional response elements (AREs). Finally, we show that Fraction 0-4 provides broad neuroprotection in organotypic brain slice models for neurodegeneration driven by amyloid precursor protein (APP) and tau implicated in Alzheimer's disease and frontotemporal dementias, respectively, in addition to ischemic injury modeled by OGD.

Natural aerosols explain seasonal and spatial patterns of Southern Ocean cloud albedo.

Atmospheric aerosols, suspended solid and liquid particles, act as nucleation sites for cloud drop formation, affecting clouds and cloud properties-ultimately influencing the cloud dynamics, lifetime, water path, and areal extent that determine the reflectivity (albedo) of clouds. The concentration N d of droplets in clouds that influences planetary albedo is sensitive to the availability of aerosol particles on which the droplets form. Natural aerosol concentrations affect not only cloud properties themselves but also modulate the sensitivity of clouds to changes in anthropogenic aerosols. It is shown that modeled natural aerosols, principally marine biogenic primary and secondary aerosol sources, explain more than half of the spatiotemporal variability in satellite-observed N d. Enhanced N d is spatially correlated with regions of high chlorophyll a, and the spatiotemporal variability in N d is found to be driven primarily by high concentrations of sulfate aerosol at lower Southern Ocean latitudes (35(o) to 45(o)S) and by organic matter in sea spray aerosol at higher latitudes (45(o) to 55(o)S). Biogenic sources are estimated to increase the summertime mean reflected solar radiation in excess of 10 W m(-2) over parts of the Southern Ocean, which is comparable to the annual mean increases expected from anthropogenic aerosols over heavily polluted regions of the Northern Hemisphere.

Artemin, a glial cell line-derived neurotrophic factor family member, induces TRPM8-dependent cold pain.

Chronic pain associated with injury or disease can result from dysfunction of sensory afferents whereby the threshold for activation of pain-sensing neurons (nociceptors) is lowered. Neurotrophic factors control nociceptor development and survival, but also induce sensitization through activation of their cognate receptors, attributable, in part, to the modulation of ion channel function. Thermal pain is mediated by channels of the transient receptor potential (TRP) family, including the cold and menthol receptor TRPM8. Although it has been shown that TRPM8 is involved in cold hypersensitivity, the molecular mechanisms underlying this pain modality are unknown. Using microarray analyses to identify mouse genes enriched in TRPM8 neurons, we found that the glial cell line-derived neurotrophic factor (GDNF) family receptor GFRα3 is expressed in a subpopulation of TRPM8 sensory neurons that have the neurochemical profile of cold nociceptors. Moreover, we found that artemin, the specific GFRα3 ligand that evokes heat hyperalgesia, robustly sensitized cold responses in a TRPM8-dependent manner in mice. In contrast, GFRα1 and GFRα2 are not coexpressed with TRPM8 and their respective ligands GDNF and neurturin did not induce cold pain, whereas they did evoke heat hyperalgesia. Nerve growth factor induced mild cold sensitization, consistent with TrkA expression in TRPM8 neurons. However, bradykinin failed to alter cold sensitivity even though its receptor expresses in a subset of TRPM8 neurons. These results show for the first time that only select neurotrophic factors induce cold sensitization through TRPM8 in vivo, unlike the broad range of proalgesic agents capable of promoting heat hyperalgesia.

Enhanced insulin clearance in mice lacking TRPM8 channels.

Blood glucose concentration is tightly regulated by the rate of insulin secretion and clearance, a process partially controlled by sensory neurons serving as metabolic sensors in relevant tissues. The activity of these neurons is regulated by the products of metabolism which regulate transmitter release, and recent evidence suggests that neuronally expressed ion channels of the transient receptor potential (TRP) family function in this critical process. Here, we report the novel finding that the cold and menthol-gated channel TRPM8 is necessary for proper insulin homeostasis. Mice lacking TRPM8 respond normally to a glucose challenge while exhibiting prolonged hypoglycemia in response to insulin. Additionally, Trpm8-/- mice have increased rates of insulin clearance compared with wild-type animals and increased expression of insulin-degrading enzyme in the liver. TRPM8 channels are not expressed in the liver, but TRPM8-expressing sensory afferents innervate the hepatic portal vein, suggesting a TRPM8-mediated neuronal control of liver insulin clearance. These results demonstrate that TRPM8 is a novel regulator of serum insulin and support the role of sensory innervation in metabolic homeostasis.

A sensory-labeled line for cold: TRPM8-expressing sensory neurons define the cellular basis for cold, cold pain, and cooling-mediated analgesia.

Many primary sensory neurons are polymodal, responding to multiple stimulus modalities (chemical, thermal, or mechanical), yet each modality is recognized differently. Although polymodality implies that stimulus encoding occurs in higher centers, such as the spinal cord or brain, recent sensory neuron ablation studies find that behavioral responses to different modalities require distinct subpopulations, suggesting the existence of modality-specific labeled lines at the level of the sensory afferent. Here we provide evidence that neurons expressing TRPM8, a cold- and menthol-gated channel required for normal cold responses in mammals, represents a labeled line solely for cold sensation. We examined the behavioral significance of conditionally ablating TRPM8-expressing neurons in adult mice, finding that, like animals lacking TRPM8 channels (Trpm8(-/-)), animals depleted of TRPM8 neurons ("ablated") are insensitive to cool to painfully cold temperatures. Ablated animals showed little aversion to noxious cold and did not distinguish between cold and a preferred warm temperature, a phenotype more profound than that of Trpm8(-/-) mice which exhibit only partial cold-avoidance and -preference behaviors. In addition to acute responses, cold pain associated with inflammation and nerve injury was significantly attenuated in ablated and Trpm8(-/-) mice. Moreover, cooling-induced analgesia after nerve injury was abolished in both genotypes. Last, heat, mechanical, and proprioceptive behaviors were normal in ablated mice, demonstrating that TRPM8 neurons are dispensable for other somatosensory modalities. Together, these data show that, although some limited cold sensitivity remains in Trpm8(-/-) mice, TRPM8 neurons are required for the breadth of behavioral responses evoked by cold temperatures.

Pharmacological blockade of TRPM8 ion channels alters cold and cold pain responses in mice.

TRPM8 (Transient Receptor Potential Melastatin-8) is a cold- and menthol-gated ion channel necessary for the detection of cold temperatures in the mammalian peripheral nervous system. Functioning TRPM8 channels are required for behavioral responses to innocuous cool, noxious cold, injury-evoked cold hypersensitivity, cooling-mediated analgesia, and thermoregulation. Because of these various roles, the ability to pharmacologically manipulate TRPM8 function to alter the excitability of cold-sensing neurons may have broad impact clinically. Here we examined a novel compound, PBMC (1-phenylethyl-4-(benzyloxy)-3-methoxybenzyl(2-aminoethyl)carbamate) which robustly and selectively inhibited TRPM8 channels in vitro with sub-nanomolar affinity, as determined by calcium microfluorimetry and electrophysiology. The actions of PBMC were selective for TRPM8, with no functional effects observed for the sensory ion channels TRPV1 and TRPA1. PBMC altered TRPM8 gating by shifting the voltage-dependence of menthol-evoked currents towards positive membrane potentials. When administered systemically to mice, PBMC treatment produced a dose-dependent hypothermia in wildtype animals while TRPM8-knockout mice remained unaffected. This hypothermic response was reduced at lower doses, whereas responses to evaporative cooling were still significantly attenuated. Lastly, systemic PBMC also diminished cold hypersensitivity in inflammatory and nerve-injury pain models, but was ineffective against oxaliplatin-induced neuropathic cold hypersensitivity, despite our findings that TRPM8 is required for the cold-related symptoms of this pathology. Thus PBMC is an attractive compound that serves as a template for the formulation of highly specific and potent TRPM8 antagonists that will have utility both in vitro and in vivo.

The relationship between Gulf War illness, brain N-acetylaspartate, and post-traumatic stress disorder.

A previous study (Haley RW, Marshall WW, McDonald GG, Daugherty MA, Petty F, Fleckenstein JL: Brain abnormalities in Gulf War syndrome: evaluation with 1H MR spectroscopy. Radiology 2000; 215: 807-817) suggested that individuals with Gulf War Illness (GWI) had reduced quantities of the neuronal marker N-acetylaspartate (NAA) in the basal ganglia and pons. This study aimed to determine whether NAA is reduced in these regions and to investigate correlations with other possible causes of GWI, such as psychological response to stress in a large cohort of Gulf War veterans. Individuals underwent tests to determine their physical and psychological health and to identify veterans with (n=81) and without (n=97) GWI. When concentrations of NAA and ratios of NAA to creatine- and choline-containing metabolites were measured in the basal ganglia and pons, no significant differences were found between veterans with or without GWI, suggesting that GWI is not associated with reduced NAA in these regions. Veterans with GWI had significantly higher rates of post-traumatic stress disorder, supporting the idea that GWI symptoms are stress related.

Scraping through the ice: uncovering the role of TRPM8 in cold transduction.

The proper detection of environmental temperatures is essential for the optimal growth and survival of organisms of all shapes and phyla, yet only recently have the molecular mechanisms for temperature sensing been elucidated. The discovery of temperature-sensitive ion channels of the transient receptor potential (TRP) superfamily has been pivotal in explaining how temperatures are sensed in vivo, and here we will focus on the lone member of this cohort, TRPM8, which has been unequivocally shown to be cold sensitive. TRPM8 is expressed in somatosensory neurons that innervate peripheral tissues such as the skin and oral cavity, and recent genetic evidence has shown it to be the principal transducer of cool and cold stimuli. It is remarkable that this one channel, unlike other thermosensitive TRP channels, is associated with both innocuous and noxious temperature transduction, as well as cold hypersensitivity during injury and, paradoxically, cold-mediated analgesia. With ongoing research, the field is getting closer to answering a number of fundamental questions regarding this channel, including the cellular mechanisms of TRPM8 modulation, the molecular context of TRPM8 expression, as well as the full extent of the role of TRPM8 in cold signaling in vivo. These findings will further our understanding of basic thermotransduction and sensory coding, and may have important implications for treatments for acute and chronic pain.

Rheological complexity in simple chain models.

Dynamical properties of short freely jointed and freely rotating chains are studied using molecular dynamics simulations. These results are combined with those of previous studies, and the degree of rheological complexity of the two models is assessed. New results are based on an improved analysis procedure of the rotational relaxation of the second Legendre polynomials of the end-to-end vector in terms of the Kohlrausch-Williams-Watts (KWW) function. Increased accuracy permits the variation of the KWW stretching exponent beta to be tracked over a wide range of state points. The smoothness of beta as a function of packing fraction eta is a testimony both to the accuracy of the analytical methods and the appropriateness of (eta(0)-eta) as a measure of the distance to the ideal glass transition at eta(0). Relatively direct comparison is made with experiment by viewing beta as a function of the KWW relaxation time tau(KWW). The simulation results are found to be typical of small molecular glass formers. Several manifestations of rheological complexity are considered. First, the proportionality of alpha-relaxation times is explored by the comparison of translational to rotational motion (i.e., the Debye-Stokes-Einstein relation), of motion on different length scales (i.e., the Stokes-Einstein relation), and of rotational motion at intermediate times to that at long time. Second, the range of time-temperature superposition master curve behavior is assessed. Third, the variation of beta across state points is tracked. Although no particulate model of a liquid is rigorously rheologically simple, we find freely jointed chains closely approximated this idealization, while freely rotating chains display distinctly complex dynamical features.

Distribution of cytochrome P4501A1-inducing chemicals in sediments of the Delaware River-Bay system, USA.

The Delaware River-Bay system, USA, was the subject of a study by the National Oceanic and Atmospheric Administration that involved chemical and biological analyses, including the use of the biomarker P450 human reporter gene system (HRGS) to document the occurrence and distribution of cytochrome P450 (CYP) 1A1-inducing compounds. Sediment extracts from 81 locations along the Delaware River, Delaware Bay and immediate coastline were tested by utilizing HRGS as an inexpensive screening test, and were also analyzed for polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls, with selected stations analyzed for dioxins and furans. Benthic community degradation has been observed when benzo[a]pyrene equivalents (BaPEq) exceeded 60 microg/g. The average levels of BaPEq for the largely industrialized upper, middle, and lower regions of the Delaware River were 107, 62, and 5 microg/g, respectively, excluding outliers. Tributaries leading into river averaged 21 microg/g BaPEq, whereas the central Bay and open coast had relatively low values (2.0 and 0.5 microg/g BaPEq, respectively). The HRGS values were highly correlated with total PAHs measured in the same sediment samples (r2 = 0.81). Overall, contamination levels consistently decreased from the upper and middle river sites as collection locations progressed down through the lower river and bay to the coast. Thus, despite the relatively high contaminant load in the river system, Delaware Bay and the immediate coastline seem to have relatively low levels of contaminants, and, therefore, impacts on the benthic organisms in the bay and coast would not be expected from these findings.