A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Oral Doses of V-7404 in Healthy Adult Volunteers.

V-7404, a direct-acting enterovirus (EV) 3C protease inhibitor, is being developed as a treatment option for serious EV infections, including infections in immunodeficient people excreting vaccine-derived polioviruses. V-7404 may be combined with pocapavir (V-073), a capsid inhibitor, to treat these infections. A phase 1 single ascending dose (SAD; n = 36) and multiple ascending dose (MAD; n = 40) study was conducted to assess the safety, tolerability, and pharmacokinetics (PK) of V-7404 in healthy adult volunteers following oral doses starting at 200 mg and escalating to 2,000 mg once daily (QD) and 2,000 mg twice daily (BID). Adverse events (AEs), vital signs, electrocardiographic findings, physical examinations, clinical laboratory values, and PK of blood samples were assessed. No notable differences in demographic and baseline characteristics were observed across the dose cohorts. A total of 35/36 participants (97.2%) completed the SAD study (1 withdrew in the placebo group), and 37/41 participants (90.2%) completed the MAD study (1 withdrew from the 2,000 mg QD and 3 withdrew from the 2,000 mg BID cohorts). No serious AEs or deaths were reported. Treatment-emergent AEs were mild or moderate in severity. Oral doses of V-7404 in all cohorts were readily absorbed and showed no significant accumulation. PK exposure increased in an approximately dose-proportional manner and appeared to be independent of time. Overall, V-7404 was well tolerated and exhibited an acceptable safety and PK profile, supporting further clinical investigation of V-7404 for the treatment of serious EV infections.

Seasonal resource pulses and the foraging depth of a Southern Ocean top predator.

Seasonal resource pulses can have enormous impacts on species interactions. In marine ecosystems, air-breathing predators often drive their prey to deeper waters. However, it is unclear how ephemeral resource pulses such as near-surface phytoplankton blooms alter the vertical trade-off between predation avoidance and resource availability in consumers, and how these changes cascade to the diving behaviour of top predators. We integrated data on Weddell seal diving behaviour, diet stable isotopes, feeding success and mass gain to examine shifts in vertical foraging throughout ice break-out and the resulting phytoplankton bloom each year. We also tested hypotheses about the likely location of phytoplankton bloom origination (advected or produced in situ where seals foraged) based on sea ice break-out phenology and advection rates from several locations within 150 km of the seal colony. In early summer, seals foraged at deeper depths resulting in lower feeding rates and mass gain. As sea ice extent decreased throughout the summer, seals foraged at shallower depths and benefited from more efficient energy intake. Changes in diving depth were not due to seasonal shifts in seal diets or horizontal space use and instead may reflect a change in the vertical distribution of prey. Correspondence between the timing of seal shallowing and the resource pulse was variable from year to year and could not be readily explained by our existing understanding of the ocean and ice dynamics. Phytoplankton advection occurred faster than ice break-out, and seal dive shallowing occurred substantially earlier than local break-out. While there remains much to be learned about the marine ecosystem, it appears that an increase in prey abundance and accessibility via shallower distributions during the resource pulse could synchronize life-history phenology across trophic levels in this high-latitude ecosystem.

Isotopes in teeth and a cryptic population of coastal freshwater seals.

Human activities threaten the biodiversity of aquatic mammals across the globe. Conservation of these species hinges on the ability to delineate movements and foraging behaviors of animals, but gaining such insights is hampered by difficulties in tracing individuals over their lives. We determined isotope ratios in teeth (87 Sr/86 Sr, 13 C/12 C, and 18 O/16 O) to examine lifelong movement and resource-use patterns of a unique freshwater population of a wide-ranging pinniped species (harbor seal [Phoca vitulina]) that resides in Iliamna Lake, Alaska (U.S.A.). This population's potentially unique migratory behavior and use of different trophic resources are unknown. The isotope ratios we measured in teeth showed that seals were born in the lake, remained lifelong residents, and relied principally on resources produced from in the lake, even when seasonally abundant and nutrient-dense spawning anadromous fish (i.e., sockeye salmon [Oncorhynchus nerka]) were available in the lake. Our results illustrate how serial isotope records in teeth, particularly 87 Sr/86 Sr ratios, can be used to quantify how coastal mammal populations exploit both freshwater and marine ecosystems. Understanding lifelong patterns of habitat and resource use is essential information when designing effective conservation plans for threatened coastal mammals. We present the Iliamna Lake harbor seals as a unique case study into how isotope records within teeth can help reveal the cryptic ecology of such a population residing in an intact ecosystem. The results also provide critical baseline information for the Kvichak River system, which is facing an uncertain future due to proposed large-scale industrial development and a rapidly changing climate.

Isotopos Dentales y una Población Críptica de Focas Costeras de Agua Dulce Resumen Las actividades humanas amenazan a la diversidad de mamíferos acuáticos en todo el mundo. La conservación de estas especies depende de la habilidad para delinear los movimientos y los comportamientos de búsqueda de alimento de los animales, pero la obtención de dicha información está obstaculizada por las dificultades en el rastreo de individuos a lo largo del transcurso de sus vidas. Determinamos la proporción de isotopos dentales (87 Sr/86 Sr, 13 C/12 C y 18 O/16 O) para examinar el movimiento a lo largo de la vida y los patrones de uso de recursos de una población única de una especie de pinnípedos de agua dulce con una distribución amplia (foca común [Phoca vitulina]), la cual reside en el lago Iliamna, Alaska (E.U.A.). Se desconocen el comportamiento migratorio potencialmente único de esta población y el uso que le dan a los diferentes recursos tróficos. La proporción de isotopos que medimos en los dientes mostró que las focas nacieron en el lago, permanecieron como residentes de toda la vida y dependieron principalmente de los recursos producidos en el lago, incluso cuando estaban disponibles en aquel lugar por razones reproductivas los peces anádromos abundantes estacionalmente y con densidad de nutrientes (es decir, el salmón rojo [Oncorhynchus nerka]). Nuestros resultados ilustran cómo los registros seriales de isotopos dentales, particularmente la proporción 87 Sr/86 Sr, pueden usarse para cuantificar cómo las poblaciones de mamíferos costeros explotan tanto los ecosistemas marinos como los de agua dulce. El entendimiento de los patrones ontogénicos del uso de recursos y de hábitat es esencial cuando se diseñan planes efectivos de conservación para los mamíferos costeros en peligro. Presentamos a las focas comunes del lago Iliamna como un estudio de caso único sobre cómo los registros de isotopos dentales pueden ayudar a revelar la ecología críptica de dicha población que reside en un ecosistema intacto. Los resultados también proporcionan información importante de línea base para el sistema el río Kvichak, el cual está enfrentando un futuro incierto debido a la propuesta de un desarrollo industrial de gran escala y al rápido clima cambiante.

Diverse papillomaviruses identified in Weddell seals.

Papillomaviridae is a diverse family of circular, double-stranded DNA (dsDNA) viruses that infect a broad range of mammalian, avian and fish hosts. While papillomaviruses have been characterized most extensively in humans, the study of non-human papillomaviruses has contributed greatly to our understanding of their pathogenicity and evolution. Using high-throughput sequencing approaches, we identified 7 novel papillomaviruses from vaginal swabs collected from 81 adult female Weddell seals (Leptonychotes weddellii) in the Ross Sea of Antarctica between 2014-2017. These seven papillomavirus genomes were amplified from seven individual seals, and six of the seven genomes represented novel species with distinct evolutionary lineages. This highlights the diversity of papillomaviruses among the relatively small number of Weddell seal samples tested. Viruses associated with large vertebrates are poorly studied in Antarctica, and this study adds information about papillomaviruses associated with Weddell seals and contributes to our understanding of the evolutionary history of papillomaviruses.

Convergence of biannual moulting strategies across birds and mammals.

Birds and mammals have developed numerous strategies for replacing worn feathers and hair. Moulting usually occurs on an annual basis; however, moults that take place twice per year (biannual moults) also occur. Here, we review the forces driving the evolution of various moult strategies, focusing on the special case of the complete biannual moult as a convergence of selection pressures across birds and mammals. Current evidence suggests that harsh environmental conditions or seasonality (e.g. larger variation in temperatures) drive evolution of a biannual moult. In turn, the biannual moult can respond to secondary selection that results in phenotypic alteration such as colour changes for mate choice dynamics (sexual selection) or camouflage requirements (natural selection). We discuss the contributions of natural and sexual selection to the evolution of biannual moulting strategies in the contexts of energetics, niche selection, functionality and physiological mechanisms. Finally, we suggest that moult strategies are directly related to species niche because environmental attributes drive the utility (e.g. thermoregulation, camouflage, social dynamics) of the hair or feathers. Functional efficiency of moult may be undermined if the pace of evolution fails to match that of the changing climate. Thus, future research should seek to understand the plasticity of moult duration and phenology, especially in the context of annual cycles.

Identification of a polyomavirus in Weddell seal (Leptonychotes weddellii) from the Ross Sea (Antarctica).

Viruses are ubiquitous in nature, however, very few have been identified that are associated with Antarctic animals. Here we report the identification of a polyomavirus in the kidney tissue of a deceased Weddell seal from the Ross Sea, Antarctica. The circular genome (5186 nt) has typical features of polyomaviruses with a small and larger T-antigen open reading frames (ORFs) and three ORFs encoding VP1, VP2 and VP3 capsid proteins. The genome of the Weddell seal polyomavirus (WsPyV) shares 85.4% genome-wide pairwise identity with a polyomavirus identified in a California sea lion. To our knowledge WsPyV is the first viral genome identified in Antarctic pinnipeds and the third polyomavirus to be identified from an Antarctic animal, the other two being from Adélie penguin (Pygoscelis adeliae) and a sharp-spined notothen (Trematomus pennellii), both sampled in the Ross sea. The GenBank accession number: KX533457.

Regional variability in diving physiology and behavior in a widely distributed air-breathing marine predator, the South American sea lion (Otaria byronia).

Our understanding of how air-breathing marine predators cope with environmental variability is limited by our inadequate knowledge of their ecological and physiological parameters. Because of their wide distribution along both coasts of the sub-continent, South American sea lions (Otaria byronia) provide a valuable opportunity to study the behavioral and physiological plasticity of a marine predator in different environments. We measured the oxygen stores and diving behavior of South American sea lions throughout most of its range, allowing us to demonstrate that diving ability and behavior vary across its range. We found no significant differences in mass-specific blood volumes of sea lions among field sites and a negative relationship between mass-specific oxygen storage and size, which suggests that exposure to different habitats and geographical locations better explains oxygen storage capacities and diving capability in South American sea lions than body size alone. The largest animals in our study (individuals from Uruguay) were the shallowest and shortest duration divers, and had the lowest mass-specific total body oxygen stores, while the deepest and longest duration divers (individuals from southern Chile) had significantly larger mass-specific oxygen stores, despite being much smaller animals. Our study suggests that the physiology of air-breathing diving predators is not fixed, but that it can be adjusted, to a certain extent, depending on the ecological setting and or habitat. These adjustments can be thought of as a 'training effect': as the animal continues to push its physiological capacity through greater hypoxic exposure, its breath-holding capacity increases.

Rapid maturation of the muscle biochemistry that supports diving in Pacific walruses (Odobenus rosmarus divergens).

Physiological constraints dictate animals' ability to exploit habitats. For marine mammals, it is important to quantify physiological limits that influence diving and their ability to alter foraging behaviors. We characterized age-specific dive limits of walruses by measuring anaerobic (acid-buffering capacity) and aerobic (myoglobin content) capacities of the muscles that power hind (longissimus dorsi) and fore (supraspinatus) flipper propulsion. Mean buffering capacities were similar across muscles and age classes (a fetus, five neonatal calves, a 3 month old and 20 adults), ranging from 41.31 to 54.14 slykes and 42.00 to 46.93 slykes in the longissimus and supraspinatus, respectively. Mean myoglobin in the fetus and neonatal calves fell within a narrow range (longissimus: 0.92-1.68 g 100 g(-1) wet muscle mass; supraspinatus: 0.88-1.64 g 100 g(-1) wet muscle mass). By 3 months post-partum, myoglobin in the longissimus increased by 79%, but levels in the supraspinatus remained unaltered. From 3 months post-partum to adulthood, myoglobin increased by an additional 26% in the longissimus and increased by 126% in the supraspinatus; myoglobin remained greater in the longissimus compared with the supraspinatus. Walruses are unique among marine mammals because they are born with a mature muscle acid-buffering capacity and attain mature myoglobin content early in life. Despite rapid physiological development, small body size limits the diving capacity of immature walruses and extreme sexual dimorphism reduces the diving capacity of adult females compared with adult males. Thus, free-ranging immature walruses likely exhibit the shortest foraging dives while adult males are capable of the longest foraging dives.

To each its own: Thermoregulatory strategy varies among neonatal polar phocids.

Cold environmental conditions and small body size promote heat loss and may create thermoregulatory challenges for marine mammals born in polar regions. However, among polar-born phocid seal species there are variations in physical attributes and environmental conditions at birth, allowing for an interesting contrast in thermoregulatory strategy. We compared thermoregulatory strategies through morphometrics, sculp attributes (conductivity and resistance), nonshivering thermogenesis (NST via uncoupling protein 1; UCP1), and muscle thermogenesis (via enzyme activity) in neonatal harp (Pagophilus groenlandicus), hooded (Cystophora cristata), and Weddell seals (Leptonychotes weddellii). Harp seals are the smallest at birth (9.8±0.7 kg), rely on lanugo (82.49±3.70% of thermal resistance), and are capable of NST through expression of UCP1 in brown adipose tissue (BAT). In contrast, hooded seal neonates (26.8±1.3 kg) have 2.06±0.23 cm of blubber, accounting for 38.19±6.07% of their thermal resistance. They are not capable of NST, as UCP1 is not expressed. The large Weddell seal neonates (31.5±4.9 kg) rely on lanugo (89.85±1.25% of thermal resistance) like harp seals, but no evidence of BAT was found. Muscle enzyme activity was highest in Weddell seal neonates, suggesting that they rely primarily on muscle thermogenesis. Similar total thermal resistance, combined with marked differences in thermogenic capacity of NST and ST among species, strongly supports that thermoregulatory strategy in neonatal phocids is more closely tied to pups' surface area to volume ratio (SA:V) and potential for early water immersion rather than mass and ambient environmental conditions.

Shifts in thermoregulatory strategy during ontogeny in harp seals (Pagophilus groenlandicus).

Heat balance can be difficult for young and/or small animals in polar regions because environmental conditions in combination with small body size or physiological immaturity can increase heat loss. We investigated how thermoregulatory patterns change with ontogeny in 5 age classes of harp seal (Pagophilus groenlandicus) from birth to post-molt to further understand the timing of thermoregulatory development in relation to their potential vulnerability to ongoing fluctuations in the extent and stability of Arctic pack ice. We measured changes in the amount, conductivity, and resistance of the seal pups׳ insulative layers (blubber and fur), the potential for endogenous heat-generation by shivering (muscle enzyme activity), and nonshivering thermogenesis (NST; brown adipose tissue (BAT) uncoupling protein 1 (UCP1) expression and mitochondrial density). There was no significant difference in blubber conductivity among age classes, though the amount of blubber insulation significantly increased from birth to weaning. Pelage conductivity was low (0.12±0.01Wm(-1)°C(-1)) except in 9-day old pups (0.40±0.08Wm(-1)°C(-1)); the significantly higher conductivity may signal the beginning of the molt, and this age group may be the most vulnerable to early water entry. Citrate synthase activity significantly increased (49.68±3.26 to 75.08±3.52µmolmin(-1)gwetweight(-1)) in the muscle; however it is unlikely that increasing a single enzyme greatly impacts heat generation. BAT of younger pups contained UCP1, though expression and mitochondrial density quickly declined, and the ability of pups to produce heat via NST was lost by weaning. While total thermal resistance did not differ, neonatal and early nursing animals gained the majority of their thermal resistance from lanugo (82.5±0.03%); however, lanugo is not insulative when wet, and NST may be important to maintain euthermia and dry the coat if early immersion in water occurs. By late nursing, blubber seems sufficient as insulation (75.87±0.01% of resistance after 4 weeks), but high conductivity of fur may be responsible for retention of UCP1 expression. Weaned animals rely on blubber insulation, and no longer need NST, as wetted fur is no longer a threat to euthermia.

Diverse papillomaviruses identified from Antarctic fur seals, leopard seals and Weddell seals from the Antarctic.

Papillomaviruses (family Papillomaviridae) are non-enveloped, circular, double-stranded DNA viruses known to infect squamous and mucosal epithelial cells. In the family Papillomaviridae there are 53 genera and 133 viral species whose members infect a variety of mammalian, avian, reptilian, and fish species. Within the Antarctic context, papillomaviruses (PVs) have been identified in Adélie penguins (Pygoscelis adeliae, 2 PVs), Weddell seals (Leptonychotes weddellii, 7 PVs), and emerald notothen (Trematomus bernacchii, 1 PV) in McMurdo Sound and Ross Island in eastern Antarctica. Here we identified 13 diverse PVs from buccal swabs of Antarctic fur seals (Arctocephalus gazella, 2 PVs) and leopard seal (Hydrurga leptonyx, 3 PVs) in western Antarctica (Antarctic Peninsula), and vaginal and nasal swabs of Weddell seals (8 PVs) in McMurdo Sound. These PV genomes group into four genera representing 11 new papillomavirus types, of which five are from two Antarctic fur seals and a leopard seal and six from Weddell seals.

Rapid postnatal development of myoglobin from large liver iron stores in hooded seals.

Hooded seals (Cystophora cristata) rely on large stores of oxygen, either bound to hemoglobin or myoglobin (Mb), to support prolonged diving activity. Pups are born with fully developed hemoglobin stores, but their Mb levels are only 25-30% of adult levels. We measured changes in muscle [Mb] from birth to 1 year of age in two groups of captive hooded seal pups, one being maintained in a seawater pool and one on land during the first 2 months. All pups fasted during the first month, but were fed from then on. The [Mb] of the swimming muscle musculus longissimus dorsi (LD) doubled during the month of fasting in the pool group. These animals had significantly higher levels and a more rapid rise in LD [Mb] than those kept on land. The [Mb] of the shoulder muscle, m. supraspinatus, which is less active in both swimming and hauled-out animals, was consistently lower than in the LD and did not differ between groups. This suggests that a major part of the postnatal rise in LD [Mb] is triggered by (swimming) activity, and this coincides with the previously reported rapid early development of diving capacity in wild hooded seal pups. Liver iron concentration, as determined from another 25 hooded seals of various ages, was almost 10 times higher in young pups (1-34 days) than in yearling animals and adults, and liver iron content of pups dropped during the first month, implying that liver iron stores support the rapid initial rise in [Mb].

Evolution of anelloviruses from a circovirus-like ancestor through gradual augmentation of the jelly-roll capsid protein.

Anelloviruses are highly prevalent in diverse mammals, including humans, but so far have not been linked to any disease and are considered to be part of the 'healthy virome'. These viruses have small circular single-stranded DNA (ssDNA) genomes and encode several proteins with no detectable sequence similarity to proteins of other known viruses. Thus, anelloviruses are the only family of eukaryotic ssDNA viruses currently not included in the realm Monodnaviria. To gain insights into the provenance of these enigmatic viruses, we sequenced more than 250 complete genomes of anelloviruses from nasal and vaginal swab samples of Weddell seal (Leptonychotes weddellii) from Antarctica and a fecal sample of grizzly bear (Ursus arctos horribilis) from the USA and performed a comprehensive family-wide analysis of the signature anellovirus protein ORF1. Using state-of-the-art remote sequence similarity detection approaches and structural modeling with AlphaFold2, we show that ORF1 orthologs from all Anelloviridae genera adopt a jelly-roll fold typical of viral capsid proteins (CPs), establishing an evolutionary link to other eukaryotic ssDNA viruses, specifically, circoviruses. However, unlike CPs of other ssDNA viruses, ORF1 encoded by anelloviruses from different genera display remarkable variation in size, due to insertions into the jelly-roll domain. In particular, the insertion between ß-strands H and I forms a projection domain predicted to face away from the capsid surface and function at the interface of virus-host interactions. Consistent with this prediction and supported by recent experimental evidence, the outermost region of the projection domain is a mutational hotspot, where rapid evolution was likely precipitated by the host immune system. Collectively, our findings further expand the known diversity of anelloviruses and explain how anellovirus ORF1 proteins likely diverged from canonical jelly-roll CPs through gradual augmentation of the projection domain. We suggest assigning Anelloviridae to a new phylum, 'Commensaviricota', and including it into the kingdom Shotokuvirae (realm Monodnaviria), alongside Cressdnaviricota and Cossaviricota.

Seasonal habitat preference and foraging behaviour of post-moult Weddell seals in the western Ross Sea.

Weddell seals (Leptonychotes weddellii) are important predators in the Southern Ocean and are among the best-studied pinnipeds on Earth, yet much still needs to be learned about their year-round movements and foraging behaviour. Using biologgers, we tagged 62 post-moult Weddell seals in McMurdo Sound and vicinity between 2010 and 2012. Generalized additive mixed models were used to (i) explain and predict the probability of seal presence and foraging behaviour from eight environmental variables, and (ii) examine foraging behaviour in relation to dive metrics. Foraging probability was highest in winter and lowest in summer, and foraging occurred mostly in the water column or just above the bottom; across all seasons, seals preferentially exploited the shallow banks and deeper troughs of the Ross Sea, the latter providing a pathway for Circumpolar Deep Water to flow onto the shelf. In addition, the probability of Weddell seal occurrence and foraging increased with increasing bathymetric slope and where water depth was typically less than 600 m. Although the probability of occurrence was higher closer to the shelf break, foraging was higher in areas closer to shore and over banks. This study highlights the importance of overwinter foraging for recouping body mass lost during the previous summer.

A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development.

The chemokine stromal cell-derived factor (SDF-1; also known as chemokine ligand 12 [CXCL12]) regulates many essential biological processes, including cardiac and neuronal development, stem cell motility, neovascularization, angiogenesis, apoptosis, and tumorigenesis. It is generally believed that SDF-1 mediates these many disparate processes via a single cell surface receptor known as chemokine receptor 4 (CXCR4). This paper characterizes an alternate receptor, CXCR7, which binds with high affinity to SDF-1 and to a second chemokine, interferon-inducible T cell alpha chemoattractant (I-TAC; also known as CXCL11). Membrane-associated CXCR7 is expressed on many tumor cell lines, on activated endothelial cells, and on fetal liver cells, but on few other cell types. Unlike many other chemokine receptors, ligand activation of CXCR7 does not cause Ca2+ mobilization or cell migration. However, expression of CXCR7 provides cells with a growth and survival advantage and increased adhesion properties. Consistent with a role for CXCR7 in cell survival and adhesion, a specific, high affinity small molecule antagonist to CXCR7 impedes in vivo tumor growth in animal models, validating this new receptor as a target for development of novel cancer therapeutics.

Iron mobilization during lactation reduces oxygen stores in a diving mammal.

The profound impacts that maternal provisioning of finite energy resources has on offspring survival have been extensively studied across mammals. This study shows that in addition to calories, high hemoprotein concentrations in diving mammals necessitates exceptional female-to-pup iron transfer. Numerous indices of iron mobilization (ferritin, serum iron, total-iron-binding-capacity, transferrin saturation) were significantly elevated during lactation in adult female Weddell seals (Leptonychotes weddellii), but not in skip-breeders. Iron was mobilized from endogenous stores for incorporation into the Weddell seal's milk at concentrations up to 100× higher than terrestrial mammals. Such high rates of iron offload to offspring drew from the female's own heme stores and led to compromised physiologic dive capacities (hemoglobin, myoglobin, and total body oxygen stores) after weaning their pups, which was further reflected in shorter dive durations. We demonstrate that lactational iron transfer shapes physiologic dive thresholds, identifying a cost of reproduction to a marine mammal.

Antioxidant capacity develops with maturation in the deep-diving hooded seal.

Maturation in hooded seals is characterized by the rapid development of their physiological diving capacity and is accompanied by increases in oxidant production but not oxidative damage. To test the hypothesis that the antioxidant system of hooded seals develops as they transition from a terrestrial to an aquatic environment, we obtained the complete cDNA sequence that encodes the NF-E2-related factor 2 (Nrf2), a central regulator of the antioxidant response, and compared Nrf2 mRNA and protein expression levels in muscle samples from neonate, weaned pups and adult hooded seals, along with glutathione (GSH) levels and the activity/protein content of the antioxidant enzymes catalase, glutathione peroxidase (GPx), peroxyredoxin VI (PrxVI), thioredoxin 1 (Trx1), thioredoxin reductase (TrxR), glutaredoxin 1 (Glrx1), glutathione disulphide reductase, glutathione S-transferase and glutamate-cysteine ligase. The Nrf2 of the hooded seal is 1822 bp long and encodes a protein of 606 amino acids with a leucine zipper domain and Keap1-mediated proteosomal degradation residues, which are key for Nrf2 function and regulation. Although neither Nrf2 mRNA nor Nrf2 nuclear protein content are higher in adults than in pups, GSH levels along with GPx, PrxVI, Trx1, TrxR and Glrx1 activity/protein content increase with maturation, suggesting that the potential for peroxide removal increases with development in hooded seals, and that these enzymes contribute to the regulation of the intracellular redox state and the prevention of oxidative damage in these deep-diving mammals.

Circoviruses and cycloviruses identified in Weddell seal fecal samples from McMurdo Sound, Antarctica.

Circoviridae is a family of circular single-stranded DNA viruses whose members infect a wide variety of hosts. While well characterized in avian and mammalian hosts, little is known about circoviruses associated with Antarctic animals. From 48 Weddell seal (Leptonychotes weddellii) fecal samples collected on the sea ice in McMurdo between Nov 2014 and Dec 2014, we identified and determined the genomes of novel viruses that fall within two genera of the family Circoviridae, i.e. Circovirus (n = 7) and Cyclovirus (n = 45). We named these viruses as werosea circovirus (WerCV) and werosea cyclovirus (WerCyV). The genomes of WerCV and WerCyV share ~63-64% genome-wide pairwise identity with classified circoviruses and cycloviruses, respectively. Based on the species demarcation threshold of 80% for members of the Circoviridae, the genomes of WerCV and WerCyV represent new species in their respective genera. Evidence indicated recombination in five of the 45 WerCyV genomes identified in this study. These are the first circoviruses found associated with Antarctic pinnipeds, adding to those recently identified associated with Adélie (Pygoscelis adeliae) and chinstrap penguins (P. antarcticus).

Thermoregulatory costs in molting Antarctic Weddell seals: impacts of physiological and environmental conditions: Themed Issue Article: Conservation of Southern Hemisphere Mammals in a Changing World.

For polar marine mammals, the energetic cost of thermoregulation depends on ambient conditions in the highly variable surrounding environment. Heat conservation strategies used by pinnipeds to reduce total heat loss include small surface area to volume ratios, the ability to limit perfusion and thick subcutaneous blubber layers. There are limits to how cool the skin surface may remain without compromising function, especially during the annual pelage molt, when hair and skin are replaced. To determine if actively molting seals incur higher thermoregulatory costs, surface temperature (ST) and heat flux (HF) were measured in 93 adult female Weddell seals (Leptonychotes weddellii) both prior to and during the active molting period using direct sensors and infrared imaging. Linear mixed-effect models revealed that ST increased significantly with increased ambient temperature and decreased wind speed (contributing 44.6 and 41.7% of the attributed variance, respectively). Seal STs were not impacted by molt status, but were maintained at 11.2 ± 0.3°C warmer than the ambient temperature. Infrared imaging results averaged 15.1 ± 1.4°C warmer than direct ST measurements. In contrast, HF was significantly higher in seals in early molting stages compared to the pre-molt season ( P < 0.001) and molt status accounted for 66.5% of the variance in HF. Thermoregulatory costs calculated from estimated basal metabolic rate and measured HF were more than double for molting seals as compared to those in pre-molt. This suggests that perfusion is increased during molt to support follicle development, despite the increased energetic costs associated with higher HF rates. Because ST, HF and thermoregulatory costs are strongly influenced by ambient conditions, molt timing is likely under selective pressure to occur during the warmest period of the year. Shifts in environmental conditions that delay molt phenology or increase HF rates could negatively impact seal populations by further increasing thermoregulatory costs.