Exosomal αvβ6 integrin is required for monocyte M2 polarization in prostate cancer

Therapeutic approaches aimed at curing prostate cancer are only partially successful given the occurrence of highly metastatic resistant phenotypes that frequently develop in response to therapies. Recently, we have described αvβ6, a surface receptor of the integrin family as a novel therapeutic target for prostate cancer; this epithelial-specific molecule is an ideal target since, unlike other integrins, it is found in different types of cancer but not in normal tissues. We describe a novel αvβ6-mediated signaling pathway that has profound effects on the microenvironment. We show that αvβ6 is transferred from cancer cells to monocytes, including β6-null monocytes, by exosomes and that monocytes from prostate cancer patients, but not from healthy volunteers, express αvβ6. Cancer cell exosomes, purified via density gradients, promote M2 polarization, whereas αvβ6 down-regulation in exosomes inhibits M2 polarization in recipient monocytes. Also, as evaluated by our proteomic analysis, αvβ6 down-regulation causes a significant increase in donor cancer cells, and their exosomes, of two molecules that have a tumor suppressive role, STAT1 and MX1/2. Finally, using the Ptenpc−/− prostate cancer mouse model, which carries a prostate epithelial-specific Pten deletion, we demonstrate that αvβ6 inhibition in vivo causes up-regulation of STAT1 in cancer cells. Our results provide evidence of a novel mechanism that regulates M2 polarization and prostate cancer progression through transfer of αvβ6 from cancer cells to monocytes through exosomes

Design and Implementation of a Thermoelectric Cooling Solution for a CCD-based NUV Spectrograph

The Colorado Ultraviolet Transit Experiment (CUTE) is a 6U CubeSat designed to obtain transit spectra of more than ten close-orbiting exoplanets. To this end, CUTE houses a near-ultraviolet (~250 – 330 nm) spectrograph based around a novel rectangular Cassegrain telescope; the spectrograph sensor is an off-the-shelf Teledyne e2v CCD. To achieve desired spectral signal-to-noise ratio (SNR), dark current is reduced by cooling the CCD to a temperature of −50 °C with a thermoelectric cooler (TEC). The TEC is driven by a constant current buck converter with an H-bridge topology for bidirectional current control. The packaging of the CCD imposes a maximum time rate of change of temperature of 5 K/min. A cascaded software control loop (discussed here) was developed that constrains this time rate of change within allowable bounds while simultaneously driving the CCD temperature to a desired setpoint. Criteria for sizing a TEC to the application and initial laboratory results are discussed, as well as digital filtering methods employed and possible solutions to integral wind-up

Nanomaterials versus ambient ultrafine particles: an opportunity to exchange toxicology knowledge

BACKGROUND: A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in in vitro models. OBJECTIVES: NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NMs, and the study of NMs provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP. METHODS: A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas. DISCUSSION: Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas in which additional research prioritization would facilitate both research fields simultaneously. CONCLUSION: There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa.info:eu-repo/semantics/publishedVersio

Towards a North Sea ecosystem component of GOOS for assessment and management: report from a strategic workshop in Bergen 5-7 September 2001

ICES and IOC have established a joint Steering Group on GOOS (SGGOOS), which also involves the European component of GOOS (EuroGOOS). To increase the efficiency and effectiveness of the use of data products from current relevant national and international monitoring of the North Sea, the workshop invited the national agencies responsible for monitoring of the North Sea to: - establish a coordinated mechanism that could add value to existing activities by integrating data from various sources (physical, chemical, biological) to aid development of an ecosystem approach, - collaborate by means of a pilot project sponsored by ICES and EuroGOOS to demonstrate the usefulness of this approach by integrating data on oceanography and fisheries

Emotional disclosure in palliative care: A scoping review of intervention characteristics and implementation factors

Background:: Emotional disclosure is the therapeutic expression of emotion. It holds potential as a means of providing psychological support. However, evidence of its efficacy in palliative settings is mixed. This may be due to variation in intervention characteristics. Aim:: To derive a greater understanding of the characteristics of potentially effective emotional disclosure-based interventions in palliative care by: (1) Developing a taxonomy of emotional disclosure-based interventions tested in people with advanced disease and (2) Mapping and linking objectives, outcomes, underlying mechanisms, and implementation factors. Design:: A scoping review drawing on Intervention Component Analysis to combine evidence from studies’ methods, results, and discussion sections. Data sources:: Six databases were searched to May 2020 including CINAHL, PsycINFO, and MEDLINE. Studies of emotional disclosure in adults with advanced disease were included. Study quality was appraised using an established tool. Results:: Seven thousand seven hundred ninety-two unique records were screened, of which 25 primary studies were included. Intervention characteristics were grouped into classes within three domains: topic of disclosure, format, and dose. Evidence was not available to determine which, if any, of the characteristics is most effective. Thematic synthesis of evidence from methods and discussion sections identified factors to consider in tailoring an emotional disclosure-based intervention to this setting, including: population characteristics (e.g. time since diagnosis), providing a safe environment, and flexibility in format. Conclusions:: This review approach facilitated a clearer understanding of factors that may be key in developing emotional disclosure-based interventions for palliative populations. Intervention Component Analysis has potential for application elsewhere to help develop evidence-based interventions.Peer reviewedFinal Published versio

Thick‑billed Murres in breeding pairs migrate and overwinter far apart but in similar photic environments

Scheduling between mates in species with long-term pair bonds can be essential for positive fitness. The annual cycle in photoperiod is the primary environmental cue used by many animals to synchronize behavior and physiology among members of a population, and animals that migrate must have similar annual schedules to ensure successful breeding. However, we know little about whether members of mated pairs in migratory species experience similar photic environments across the year, which could allow for synchronization in annual phenology. Here, we used light-based geolocation to estimate positions of mated pairs of Thick-billed Murres (Uria lomvia, a seabird a.k.a. Brünnich’s Guillemot) which bred above the northern polar circle in Greenland. We tested the hypothesis that individuals in mated pairs occur in more similar locations and photic environments than randomly matched females and males. We found no difference in the amount of spatial separation or in the photic environment between mates and randomized heterosexual pairings. In general, the distance between females and males ranged from 1,198.5 km during August to 737.4 km during January. The sexes remained in photic environments with highly correlated photoperiods and moderately correlated times of solar noon in UTC. The spatial separation of, but similar photic environments experienced by, female and male murres regardless of pair status is probably adaptive by facilitating the synchronization of annual schedules between sexes, while allowing individuals in mated pairs the freedom to pursue the best foraging opportunities during migration and overwintering independent of their mate. Greenland · Pair migration · Photoperiod · Seabird · Thick-billed Murre · Uria lomviaThick‑billed Murres in breeding pairs migrate and overwinter far apart but in similar photic environmentspublishedVersio

Multiplexed droplet Interface bilayer formation

We present a simple method for the multiplexed formation of droplet interface bilayers (DIBs) using a mechanically operated linear acrylic chamber array. To demonstrate the functionality of the chip design, a lipid membrane permeability assay is performed. We show that multiple, symmetric DIBs can be created and separated using this robust low-cost approach

A single-particle characterization of a mobile Versatile Aerosol Concentration Enrichment System for exposure studies

BACKGROUND: An Aerosol Time-of-Flight Mass Spectrometer (ATOFMS) was used to investigate the size and chemical composition of fine concentrated ambient particles (CAPs) in the size range 0.2–2.6 μm produced by a Versatile Aerosol Concentration Enrichment System (VACES) contained within the Mobile Ambient Particle Concentrator Exposure Laboratory (MAPCEL). The data were collected during a study of human exposure to CAPs, in Edinburgh (UK), in February-March 2004. The air flow prior to, and post, concentration in the VACES was sampled in turn into the ATOFMS, which provides simultaneous size and positive and negative mass spectral data on individual fine particles. RESULTS: The particle size distribution was unaltered by the concentrator over the size range 0.2–2.6 μm, with an average enrichment factor during this study of ~5 (after dilution of the final air stream). The mass spectra from single particles were objectively grouped into 20 clusters using the multivariate K-means algorithm and then further grouped manually, according to similarity in composition and time sequence, into 8 main clusters. The particle ensemble was dominated by pure and reacted sea salt and other coarse inorganic dusts (as a consequence of the prevailing maritime-source climatology during the study), with relatively minor contributions from carbonaceous and secondary material. Very minor variations in particle composition were noted pre- and post-particle concentration, but overall there was no evidence of any significant change in particle composition. CONCLUSION: These results confirm, via single particle analysis, the preservation of the size distribution and chemical composition of fine ambient PM in the size range 0.2–2.6 μm after passage through the VACES concentration instrumentation

Rheological droplet interface bilayers (rheo-DIBs): Probing the unstirred water layer effect on membrane permeability via spinning disk induced shear stress

A new rheological droplet interface bilayer (rheo-DIB) device is presented as a tool to apply shear stress on biological lipid membranes. Despite their exciting potential for affecting high-throughput membrane translocation studies, permeability assays conducted using DIBs have neglected the effect of the unstirred water layer (UWL). However as demonstrated in this study, neglecting this phenomenon can cause significant underestimates in membrane permeability measurements which in turn limits their ability to predict key processes such as drug translocation rates across lipid membranes. With the use of the rheo-DIB chip, the effective bilayer permeability can be modulated by applying shear stress to the droplet interfaces, inducing flow parallel to the DIB membranes. By analysing the relation between the effective membrane permeability and the applied stress, both the intrinsic membrane permeability and UWL thickness can be determined for the first time using this model membrane approach, thereby unlocking the potential of DIBs for undertaking diffusion assays. The results are also validated with numerical simulations

Reducing Personal Exposure to Particulate Air Pollution Improves Cardiovascular Health in Patients with Coronary Heart Disease

Background: Air pollution exposure increases cardiovascular morbidity and mortality and is a major global public health concern