Plastic pollution is distributed patchily around the world's oceans. Likewise, marine organisms that are vulnerable to plastic ingestion or entanglement have uneven distributions. Understanding where ...wildlife encounters plastic is crucial for targeting research and mitigation. Oceanic seabirds, particularly petrels, frequently ingest plastic, are highly threatened, and cover vast distances during foraging and migration. However, the spatial overlap between petrels and plastics is poorly understood. Here we combine marine plastic density estimates with individual movement data for 7137 birds of 77 petrel species to estimate relative exposure risk. We identify high exposure risk areas in the Mediterranean and Black seas, and the northeast Pacific, northwest Pacific, South Atlantic and southwest Indian oceans. Plastic exposure risk varies greatly among species and populations, and between breeding and non-breeding seasons. Exposure risk is disproportionately high for Threatened species. Outside the Mediterranean and Black seas, exposure risk is highest in the high seas and Exclusive Economic Zones (EEZs) of the USA, Japan, and the UK. Birds generally had higher plastic exposure risk outside the EEZ of the country where they breed. We identify conservation and research priorities, and highlight that international collaboration is key to addressing the impacts of marine plastic on wide-ranging species.
The acquired form of the long-QT syndrome (LQTS) is a major safety consideration for the development and subsequent use of both cardiac and non-cardiac drugs; it is usually associated with ...pharmacological inhibition of cardiac
HERG-encoded potassium channels. Clomiphene is an anti-estrogen agent used extensively in the treatment of infertility and is not associated with a risk of QT interval prolongation, in contrast to a structurally related compound tamoxifen. We describe here a potent inhibitory effect (IC
50=0.18
μM) of clomiphene on HERG ionic current (
I
HERG) recorded from a mammalian cell line expressing HERG channels. Inhibition of
I
HERG by clomiphene showed voltage-dependence and developed quickly following membrane depolarisation, indicating contingency of block on HERG channel gating. At 100
nM, clomiphene and the related anti-estrogen tamoxifen produced similar levels of
I
HERG blockade (
p>0.05). Experiments on guinea-pig isolated perfused hearts revealed that, despite its inhibitory action on
I
HERG, clomiphene produced no significant effect at 1
μM on uncorrected QT interval (
p>0.1) nor on rate-corrected QT interval (QT
c;
p>0.1 for QT
c determined using Van de Water’s formula). The disparity between clomiphene’s potent
I
HERG inhibition and its lack of effect on the QT interval underscores the notion that
I
HERG pharmacology may best be used alongside other screening methods when investigating the QT-prolonging tendency and related cardiotoxicity of non-cardiac drugs.
Pyrethroid insecticides are known to modify neuronal sodium channels, inducing persistent, steady-state sodium current at depolarized membrane potentials. Cardiac myocytes are also rich in sodium ...channels but comparatively little is known about the effect of pyrethroids on the heart, or on the cardiac sodium channel isoform. In the present study therefore, we determined the actions of type I and type II pyrethroids against rat and guinea pig ventricular myocytes under current and voltage clamp, and on isolated perfused rat hearts. In myocytes, tefluthrin (type I) and fenpropathrin and alpha-cypermethrin (type II) prolonged action potentials and evoked afterdepolarizations. The time course of sodium current (I(Na)) was also prolonged by these compounds. Pyrethroids delayed I(Na) inactivation, when measured under selective conditions as current sensitive to 30 microM tetrodotoxin, by increasing the proportion of slowly inactivating current at the expense of fast inactivating current. Further experiments, focusing on fenpropathrin, revealed that its effects on I(Na) inactivation time course were dose-dependent, and the Na(+) "window-current" was increased in its presence. In unstimulated, isolated hearts perfused with the same pyrethroids, the variability in contraction amplitude increased due to variations in the intervals between heartbeats. These potentially arrhythmogenic changes are consistent with the effects observed at the cellular level. The type I pyrethroid tetramethrin had little effect in any of the preparations. These findings suggest that some pyrethroids possess considerable mammalian cardiac arrhythmogenic potential, the manifestation of which in vivo may depend on the route of exposure.
Migratory waterbirds require an effectively conserved cohesive network of wetland areas throughout their range and life-cycle. Under rapid climate change, protected area (PA) networks need to be able ...to accommodate climate-driven range shifts in wildlife if they are to continue to be effective in the future. Thus, we investigated geographical variation in the relationship between local temperature anomaly and the abundance of 61 waterbird species during the wintering season across Europe and North Africa during 1990–2015. We also compared the spatio-temporal effects on abundance of sites designated as PAs, Important Bird and Biodiversity Areas (IBAs), both, or neither designation (Unlisted). Waterbird abundance was positively correlated with temperature anomaly, with this pattern being strongest towards north and east Europe. Waterbird abundance was higher inside IBAs, whether they were legally protected or not. Trends in waterbird abundance were also consistently more positive inside both protected and unprotected IBAs across the whole study region, and were positive in Unlisted wetlands in southwestern Europe and North Africa. These results suggest that IBAs are important sites for wintering waterbirds, but also that populations are shifting to unprotected wetlands (some of which are IBAs). Such IBAs may therefore represent robust candidate sites to expand the network of legally protected wetlands under climate change in north-eastern Europe. These results underscore the need for monitoring to understand how the effectiveness of site networks is changing under climate change.
A country-by-country review of seabird mortality from longline fishing in the Mediterranean Sea and in Macaronesian waters shows a paucity of data. Of 12 Mediterranean countries known to undertake ...longlining, seabird mortality is only reported for six: France, Greece, Italy, Malta, Spain and Tunisia. Seabird mortality from longlining has been reported from the Azores (Portugal) but not from the other Macaronesian Islands. Only for one country, Spain, is information on the levels of mortality available, suggesting that 4-6% of the local breeding population of Cory's shearwater Calonectris diomedea may be killed annually, a level considered unsustainable for the long-term persistence of colonies. Cory's shearwater is the most commonly affected species, although a number of Larus gull species are also being caught. There is insufficient knowledge to conclude whether any seabird species is at conservation risk within the region, but concern is expressed for Cory's shearwater. It is recommended that Mediterranean and Macaronesian countries conduct assessments of their longline fisheries and seabird mortality in terms of the Food and Agriculture Organization's International Plan of Action - Seabirds. Regional fishery organisations, such as ICCAT and GFCM, should commence the collection of seabird mortality data. A "longline action plan" for the affected seabird species should be produced.Original Abstract: Mortalidad de aves marinas en palangres del mar Mediterraneo e islas macaronesias: revision y propuestas de futuro. - Este trabajo presenta una revision de la escasa informacion disponible sobre mortalidad de aves marinas en las flotas palangreras del mar Mediterraneo y Macaronesia. de los 12 paises mediterraneos que disponen de flota palangrera tan solo 6 han aportado informacion sobre mortalidad de aves marinas: Francia, Grecia, Italia, Malta, Espana y Tunez. Tambien se sabe que existe mortalidad de aves marinas en las islas Azores (Portugal) pero no en el resto de las islas de la Macaronesia. Tan solo Espana dispone de informacion sobre niveles de mortalidad. Es posible que entre el 4-6% de la poblacion reproductora local de pardela cenicienta Calonectris diomedea muera en el palangre anualmente, un nivel que se considera insostenible para la persistencia a largo plazo de las colonias. La pardela cenicienta es la especie mas afectada, aunque tambien se capturan gaviotas del genero Larus. Aunque no se sabe lo suficiente como para concluir si alguna especie de ave marina esta amenazada localmente por el palangre, se sugiere que la pardela cenicienta si puede estarlo. Se recomienda que los paises mediterraneos y macaronesicos lleven a cabo valoraciones de sus pesquerias de palangre y de la mortalidad de aves marinas en los terminos de los planes internacionales de accion de la FAO. Las organizaciones pesqueras regionales, tales como la ICCAT y la GFCM, deberian comenzar a compilar informacion sobre mortalidad de aves marinas. Se deberia redactar un plan de acccion para las especies de aves marinas afectadas. Palabras clave: aves marinas, pesca de palangre, conservacion, mediterraneo, Macaronesia.
Satellite tags were attached to ten juvenile Yelkouan Shearwaters from a breeding colony in Malta to study post-fledging dispersal patterns. Of the eight birds with usable data, all moved eastwards ...almost immediately after leaving their nest sites. The majority of birds migrated to the islands off the western coast of Greece with one then moving on into the Aegean Sea and another to the South Adriatic Basin. While most birds migrated to Greek waters, two followed a different route, undertaking a wide circuit of the eastern Mediterranean and eventually ending up along the northern coast of Africa. The bird that transmitted for the longest period (68 days) was last recorded in the northern Aegean where it had spent the majority of the time. This study has shown that Maltese Yelkouan Shearwaters range over a large area during the first few weeks of fledging and follow widely varying routes. It has also demonstrated the importance of Greek waters for juvenile Yelkouans from Maltese colonies. The difficulty in tracking juvenile Yelkouan Shearwaters using this method has been highlighted by this study, and it is suggested that further methods are explored to track juvenile birds during the months after fledging.
Defects in growth hormone secretion or signaling in mice are associated with decreased body weights (dwarfism), increased longevity, increased resistance to stress, and decreases in factors that ...contribute to cardiovascular disease and cancer. Peroxisome proliferators (PP) alter a subset of these changes in wild-type mice through activation of the nuclear receptor family member PP-activated receptor α (PPARα). We tested the hypothesis that an overlap in the transcriptional programs between untreated dwarf mice and PP-treated wild-type mice underlies these similarities. Using transcript profiling, we observed a statistically significant overlap in the expression of genes differentially regulated in control Snell dwarf mice (Pit-1dw) compared with phenotypically normal heterozygote (+/dw) control mice and those altered by the PP 4-chloro-6-(2,3-xylidino)-2-pyrimidinyl)thioacetic acid (WY-14,643) in +/dw mice. The genes included those involved in β- and ω-oxidation of fatty acids (Acox1, Cyp4a10, Cyp4a14) and those involved in stress responses (the chaperonin, T-complex protein1epsilon) and cardiovascular disease (fibrinogen). The levels of some of these gene products were also altered in other dwarf mouse models, including Ames, Little, and growth hormone receptor-null mice. The constitutive increases in PPARα-regulated genes may be partly caused by increased expression of PPARα mRNA and protein as observed in the livers of control Snell dwarf mice. These results indicate that some of the beneficial effects associated with the dwarf phenotype may be caused by constitutive activation of PPARα and regulated genes.
The aim of this study was to determine the effects of the antiestrogen agent clomiphene on cardiac anionic and cationic sarcolemmal ion channels. Whole-cell recordings were made from rat and guinea ...pig ventricular myocytes. Clomiphene inhibited the volume-regulated chloride current I(Cl,vol), activated by cell swelling after hypotonic shock (approximately 145 mOsM) with an IC(50) value of approximately 9.4 microM. In contrast, at concentrations up to 100 microM, clomiphene failed to inhibit both the chloride current activated by cyclic AMP (I(Cl,cAMP)) and the anionic background current (I(AB)). At 10 microM, clomiphene blocked the voltage-gated fast sodium current and the L-type calcium current (I(Ca,L)) in both species. The voltage-independent fractional block of I(Ca,L) induced by clomiphene (10 microM) was approximately 82%, this concentration also inhibited the inwardly rectifying K(+) current with a fractional current block of approximately 26% at -90 mV. Fractional block of outward current at +70 mV in rat was approximately 25%, implying that delayed rectifying K(+) channels were also affected by clomiphene. We conclude that clomiphene shows selectivity for I(Cl,vol) over I(Cl,cAMP) and I(AB) and therefore represents a useful tool for studying chloride conductances in isolated ventricular myocytes with interfering currents blocked. However, due to its effects on cation conductances it would be of little value in this regard for other types of in vitro or in vivo experiments.
Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, ...germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition.
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