Plastic ingestion in adult and fledgling Manx Shearwaters Puffinus puffinus on Skomer Island, Wales

Plastic debris is ubiquitous in the marine environment, and seabirds are among the most impacted marine vertebrates. Plastic ingestion was investigated in an internationally-important breeding population of Manx Shearwaters Puffinus puffinus on Skomer Island, Wales in 2018–19. Opportunistic necropsies were carried out on a total of 34 birds to collect contents of the gastrointestinal tract: 13 adults in April – July 2018 and 12 fledglings during September 2019, and a further nine opportunistic necropsies carried out from adults in July – September 2018. The presence, quantity, size and colour of plastic in the gastrointestinal tract was investigated. Plastic was found in 71% of stomach contents (68% of adults, 75% of fledglings). Adults were found to have larger plastic pieces in their gastrointestinal tract than fledglings, and lighter birds had larger pieces of plastic in their tracts than heavier birds. This study shows that Manx Shearwaters on Skomer Island are vulnerable to plastic ingestion, and that adults are likely to pass plastic to their chicks

Climate impacts of energy technologies depend on emissions timing

Energy technologies emit greenhouse gases with differing radiative efficiencies and atmospheric lifetimes. Standard practice for evaluating technologies, which uses the global warming potential (GWP) to compare the integrated radiative forcing of emitted gases over a fixed time horizon, does not acknowledge the importance of a changing background climate relative to climate change mitigation targets. Here we demonstrate that the GWP misvalues the impact of CH[subscript 4]-emitting technologies as mid-century approaches, and we propose a new class of metrics to evaluate technologies based on their time of use. The instantaneous climate impact (ICI) compares gases in an expected radiative forcing stabilization year, and the cumulative climate impact (CCI) compares their time-integrated radiative forcing up to a stabilization year. Using these dynamic metrics, we quantify the climate impacts of technologies and show that high-CH[subscript 4]-emitting energy sources become less advantageous over time. The impact of natural gas for transportation, with CH[subscript 4] leakage, exceeds that of gasoline within 1–2 decades for a commonly cited 3 W m[superscript −2] stabilization target. The impact of algae biodiesel overtakes that of corn ethanol within 2–3 decades, where algae co-products are used to produce biogas and corn co-products are used for animal feed. The proposed metrics capture the changing importance of CH[subscript 4] emissions as a climate threshold is approached, thereby addressing a major shortcoming of the GWP for technology evaluation.New England University Transportation Center (DOT Grant DTRT07-G-0001

Deep diversification of an AAV capsid protein by machine learning.

Modern experimental technologies can assay large numbers of biological sequences, but engineered protein libraries rarely exceed the sequence diversity of natural protein families. Machine learning (ML) models trained directly on experimental data without biophysical modeling provide one route to accessing the full potential diversity of engineered proteins. Here we apply deep learning to design highly diverse adeno-associated virus 2 (AAV2) capsid protein variants that remain viable for packaging of a DNA payload. Focusing on a 28-amino acid segment, we generated 201,426 variants of the AAV2 wild-type (WT) sequence yielding 110,689 viable engineered capsids, 57,348 of which surpass the average diversity of natural AAV serotype sequences, with 12-29 mutations across this region. Even when trained on limited data, deep neural network models accurately predict capsid viability across diverse variants. This approach unlocks vast areas of functional but previously unreachable sequence space, with many potential applications for the generation of improved viral vectors and protein therapeutics

Phenotypic Evidence of Emerging Ivermectin Resistance in Onchocerca volvulus

Onchocerciasis, commonly known as river blindness, is caused by the filarial nematode Onchocerca volvulus and is transmitted by a blackfly vector. Over 37 million people are thought to be infected, with over 90 million at risk. Infection predominantly occurs in sub-Saharan Africa. Foci also exist in the Arabian Peninsula and Central and South America. Ivermectin, the sole pharmaceutical available for mass chemotherapy, has been used on a community basis for annual or semi-annual treatment since 1987. Multiple treatments with ivermectin kill the microfilariae that are responsible for the pathology of onchocerciasis. More importantly, ivermectin suppresses the reproductive activity of the adult female worms, thus delaying or preventing the repopulation of the skin with new microfilariae and thereby reducing transmission. This study extends earlier reports of sub-optimal responses to ivermectin by examining repopulation levels of microfilaria one year after treatment, worm burdens per nodule, the age structure of adult female worms recovered from nodules, and the reproductive status of adult female worms 90 days after ivermectin treatment. In some communities which have shown a pattern of sub-optimal response to treatment, the data is consistent with an emergence of ivermectin non response or resistance manifested by a loss of the effect of ivermectin on the suppression of parasite reproduction

Post-treatment skin reactions reported by cancer patients differ by race, not by treatment or expectations

Cancer patients may experience skin problems while undergoing chemotherapy and radiation therapy. Frequency of skin reactions may be influenced by skin pigmentation and psychological factors. A Symptom Inventory completed by 656 cancer patients nationwide before and after chemotherapy, radiation therapy, or chemotherapy plus radiation therapy was analysed to determine if treatment type, race (Black vs White), and pretreatment expectations influenced post-treatment skin reactions. Subsequent analysis of a local Symptom Inventory completed weekly for 5 weeks by 308 patients receiving radiation therapy examined severity of reported skin reactions. Significantly more patients receiving radiation therapy had stronger expectations of skin problems (62%) than patients receiving chemotherapy (40%, P=0.001) or chemotherapy plus radiation therapy (45%, P=0.003). Overall, expectations did not correlate with patient reported post-treatment skin problems in white (r=0.014, P=0.781) or black (r=0.021, P=0.936) patients. Although no significant difference was found between black and white patients in their pretreatment expectations of skin problems (P=0.32), black patients (10 out of 18, 56%) reported more skin problems than white patients (90 out of 393, 23%, P=0.001). Similarly, the local study showed that significantly more black patients (1 out of 5, 20%) reported severe skin reactions at the treatment site than white patients (12 out of 161, 8%). A direct correlation was observed between severity of skin problems and pain at the treatment site (r=0.541, P<0.001). Total radiation exposure did not significantly correlate with the report of skin problems at the treatment site for white or black patients. Overall, black patients reported more severe post-treatment skin problems than white patients. Our results suggest that symptom management for post-treatment skin reactions in cancer patients receiving radiation treatment could differ depending on their racial background

High CO2 and Silicate Limitation Synergistically Increase the Toxicity of Pseudo-nitzschia fraudulenta

Anthropogenic CO2 is progressively acidifying the ocean, but the responses of harmful algal bloom species that produce toxins that can bioaccumulate remain virtually unknown. The neurotoxin domoic acid is produced by the globally-distributed diatom genus Pseudo-nitzschia. This toxin is responsible for amnesic shellfish poisoning, which can result in illness or death in humans and regularly causes mass mortalities of marine mammals and birds. Domoic acid production by Pseudo-nitzschia cells is known to be regulated by nutrient availability, but potential interactions with increasing seawater CO2 concentrations are poorly understood. Here we present experiments measuring domoic acid production by acclimatized cultures of Pseudo-nitzschia fraudulenta that demonstrate a strong synergism between projected future CO2 levels (765 ppm) and silicate-limited growth, which greatly increases cellular toxicity relative to growth under modern atmospheric (360 ppm) or pre-industrial (200 ppm) CO2 conditions. Cellular Si∶C ratios decrease with increasing CO2, in a trend opposite to that seen for domoic acid production. The coastal California upwelling system where this species was isolated currently exhibits rapidly increasing levels of anthropogenic acidification, as well as widespread episodic silicate limitation of diatom growth. Our results suggest that the current ecosystem and human health impacts of toxic Pseudo-nitzschia blooms could be greatly exacerbated by future ocean acidification and ‘carbon fertilization’ of the coastal ocean

Visible Light Responsive Photocatalyst Induces Progressive and Apical-Terminus Preferential Damages on Escherichia coli Surfaces

BACKGROUND: Recent research shows that visible-light responsive photocatalysts have potential usage in antimicrobial applications. However, the dynamic changes in the damage to photocatalyzed bacteria remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: Facilitated by atomic force microscopy, this study analyzes the visible-light driven photocatalyst-mediated damage of Escherichia coli. Results show that antibacterial properties are associated with the appearance of hole-like structures on the bacteria surfaces. Unexpectedly, these hole-like structures were preferentially induced at the apical terminus of rod shaped E. coli cells. Differentiating the damages into various levels and analyzing the percentage of damage to the cells showed that photocatalysis was likely to elicit sequential damages in E. coli cells. The process began with changing the surface properties on bacterial cells, as indicated in surface roughness measurements using atomic force microscopy, and holes then formed at the apical terminus of the cells. The holes were then subsequently enlarged until the cells were totally transformed into a flattened shape. Parallel experiments indicated that photocatalysis-induced bacterial protein leakage is associated with the progression of hole-like damages, further suggesting pore formation. Control experiments using ultraviolet light responsive titanium-dioxide substrates also obtained similar observations, suggesting that this is a general phenomenon of E. coli in response to photocatalysis. CONCLUSION/SIGNIFICANCE: The photocatalysis-mediated localization-preferential damage to E. coli cells reveals the weak points of the bacteria. This might facilitate the investigation of antibacterial mechanism of the photocatalysis

Inhibition of radiation induced migration of human head and neck squamous cell carcinoma cells by blocking of EGF receptor pathways

<p>Abstract</p> <p>Background</p> <p>Recently it has been shown that radiation induces migration of glioma cells and facilitates a further spread of tumor cells locally and systemically. The aim of this study was to evaluate whether radiotherapy induces migration in head and neck squamous cell carcinoma (HNSCC). A further aim was to investigate the effects of blocking the epidermal growth factor receptor (EGFR) and its downstream pathways (Raf/MEK/ERK, PI3K/Akt) on tumor cell migration in vitro.</p> <p>Methods</p> <p>Migration of tumor cells was assessed via a wound healing assay and proliferation by a MTT colorimeritric assay using 3 HNSCC cell lines (BHY, CAL-27, HN). The cells were treated with increasing doses of irradiation (2 Gy, 5 Gy, 8 Gy) in the presence or absence of EGF, EGFR-antagonist (AG1478) or inhibitors of the downstream pathways PI3K (LY294002), mTOR (rapamycin) and MEK1 (PD98059). Biochemical activation of EGFR and the downstream markers Akt and ERK were examined by Western blot analysis.</p> <p>Results</p> <p>In absence of stimulation or inhibition, increasing doses of irradiation induced a dose-dependent enhancement of migrating cells (p < 0.05 for the 3 HNSCC cell lines) and a decrease of cell proliferation (p < 0.05 for the 3 HNSCC cell lines). The inhibition of EGFR or the downstream pathways reduced cell migration significantly (almost all p < 0.05 for the 3 HNSCC cell lines). Stimulation of HNSCC cells with EGF caused a significant increase in migration (p < 0.05 for the 3 HNSCC cell lines). After irradiation alone a pronounced activation of EGFR was observed by Western blot analysis.</p> <p>Conclusion</p> <p>Our results demonstrate that the EGFR is involved in radiation induced migration of HNSCC cells. Therefore EGFR or the downstream pathways might be a target for the treatment of HNSCC to improve the efficacy of radiotherapy.</p

A Novel Non-Lens βγ−Crystallin and Trefoil Factor Complex from Amphibian Skin and Its Functional Implications

In vertebrates, non-lens betagamma-crystallins are widely expressed in various tissues, but their functions are unknown. The molecular mechanisms of trefoil factors, initiators of mucosal healing and being greatly involved in tumorigenesis, have remained elusive.A naturally existing 72-kDa complex of non-lens betagamma-crystallin (alpha-subunit) and trefoil factor (beta-subunit), named betagamma-CAT, was identified from frog Bombina maxima skin secretions. Its alpha-subunit and beta-subunit (containing three trefoil factor domains), with a non-covalently linked form of alphabeta(2), show significant sequence homology to ep37 proteins, a group of non-lens betagamma-crystallins identified in newt Cynops pyrrhogaster and mammalian trefoil factors, respectively. betagamma-CAT showed potent hemolytic activity on mammalian erythrocytes. The specific antiserum against each subunit was able to neutralize its hemolytic activity, indicating that the two subunits are functionally associated. betagamma-CAT formed membrane pores with a functional diameter about 2.0 nm, leading to K(+) efflux and colloid-osmotic hemolysis. High molecular weight SDS-stable oligomers (>240-kDa) were detected by antibodies against the alpha-subunit with Western blotting. Furthermore, betagamma-CAT showed multiple cellular effects on human umbilical vein endothelial cells. Low dosages of betagamma-CAT (25-50 pM) were able to stimulate cell migration and wound healing. At high concentrations, it induced cell detachment (EC(50) 10 nM) and apoptosis. betagamma-CAT was rapidly endocytosed via intracellular vacuole formation. Under confocal microscope, some of the vacuoles were translocated to nucleus and partially fused with nuclear membrane. Bafilomycin A1 (a specific inhibitor of the vacuolar-type ATPase) and nocodazole (an agent of microtuble depolymerizing), while inhibited betagamma-CAT induced vacuole formation, significantly inhibited betagamma-CAT induced cell detachment, suggesting that betagamma-CAT endocytosis is important for its activities.These findings illustrate novel cellular functions of non-lens betagamma-cyrstallins and action mechanism via association with trefoil factors, serving as clues for investigating the possible occurrence of similar molecules and action mechanisms in mammals

Cognition based bTBI mechanistic criteria; a tool for preventive and therapeutic innovations

Blast-induced traumatic brain injury has been associated with neurodegenerative and neuropsychiatric disorders. To date, although damage due to oxidative stress appears to be important, the specific mechanistic causes of such disorders remain elusive. Here, to determine the mechanical variables governing the tissue damage eventually cascading into cognitive deficits, we performed a study on the mechanics of rat brain under blast conditions. To this end, experiments were carried out to analyse and correlate post-injury oxidative stress distribution with cognitive deficits on a live rat exposed to blast. A computational model of the rat head was developed from imaging data and validated against in vivo brain displacement measurements. The blast event was reconstructed in silico to provide mechanistic thresholds that best correlate with cognitive damage at the regional neuronal tissue level, irrespectively of the shape or size of the brain tissue types. This approach was leveraged on a human head model where the prediction of cognitive deficits was shown to correlate with literature findings. The mechanistic insights from this work were finally used to propose a novel helmet design roadmap and potential avenues for therapeutic innovations against blast traumatic brain injury