Single domain shark antibodies that bind to the transferrin receptor 1 (TfR1) on brain endothelial cells have been used to shuttle antibodies and other cargos across the blood brain barrier (BBB) to the brain. For these studies the TXB4 brain shuttle was fused to a TrkB neurotrophin receptor agonist antibody. The TXB4-TrkB fusion retained potent agonist activity at its cognate receptor and after systemic administration showed a 12-fold increase in brain levels over the unmodified antibody. Only the TXB4-TrkB antibody fusion was detected within the brain and localized to TrkB positive cells in the cortex and tyrosine hydroxylase (TH) positive dopaminergic neurons in the substantia nigra pars compacta (SNc), where it was associated with activated ERK1/2 signaling. When tested in the 6-hydroxydopamine (6-OHDA) mouse model of Parkinson's disease (PD), TXB4-TrkB, but not the unmodified antibody, completely prevented the 6-OHDA induced death of TH positive neurons in the SNc. In conclusion, the fusion of the TXB4 brain shuttle allows a TrkB agonist antibody to reach neuroprotective concentrations in the brain parenchyma following systemic administration.

Micronekton of the mesopelagic zone (200 m-1000 m depth) play a central role in most aspects of global marine ecology linking epipelagic and deep scattering layers as planktivores, carnivores and principal prey to both shallow diving and deep living apex predators. Yet, despite this critical role and conspicuous presence, little is known regarding most aspects of mesopelagic community ecology, including habitat associations at sub-basin spatial scales. Here we address several aspects of these data deficiencies in the eastern Bering Sea mesopelagic - a highly productive subarctic marine ecosystem home to multiple protected predator species and large commercial fisheries. Through 41 midwater trawls conducted at 250 m, 500 m and 1000 m depths during May of 1999 and 2000, and a series of generalized linear models and cluster analyses, we describe the influence of remotely sensed oceanographic habitat variables on the diel distribution, relative abundance and community composition of 30 species of mesopelagic fish and squid in 3 contrasting study areas. We then project the total energy available to predators at depth and across the eastern Bering Sea Basin based on the identified habitat constraints. Fishes from the families Bathylagidae and Myctophidae, and squids from the Gonatidae dominated the 72 species catch biomass (n = 225,000, 2,100 kg). The six most abundant species were equally divided between each of the three dominant families and are also the most highly represented mesopelagic species in eastern Bering Sea pelagic predator diets. Their association with surface habitat variables describe a complex and multifaceted relationship between physical/biological predictors and the total mesopelagic energy field during the spring bloom period in this ecosystem. Leuroglossus schmidti, Bathylagus pacificus, Stenobrachius leucopsaurus, S. nannochir, Gonatopsis borealis and Eogonatus tinro contrast in the suite of physical and biological variables that they respond to, and also in the character of their response. Although L. schmidti is of moderate caloric value, it expressed the greatest overall energy signature at all depths due to its overwhelming biomass, and response to the presence of specific, variable habitat conditions across extensive portions of the study area. Interannual variability in habitat variables forecasted a pronounced redistribution of dominant species and thereby total mesopelagic energy content - providing a potential mechanism for shifts in central-place predator habitat use, energy expenditure, and diet. The known relevance of mesopelagic species as prey and the energetic potential for apex predators foraging in the Basin illustrates a cautionary narrative regarding unregulated harvest of biota from this poorly understood and critically important oceanic zone.

This study illuminates historical diet and foraging locations of endangered western U.S. stock Steller sea lions (Eumetopias jubatus (Schreber, 1776)). Prey were identified from stomachs of 22 males collected in the eastern Bering Sea from the ice edge in March 1985 and nearshore St. Paul Island in September–October 1985 and 1986. Percent frequency of occurrence (PFO) and percent number (PN) were highest for walleye pollock (Gadus chalcogrammus Pallas, 1814; PFO 69%, PN 15%, mean length 17 cm), Pacific herring (Clupea pallasii Valenciennes in Cuvier and Valenciennes, 1847; PFO 62%, PN 16%, mean length 26 cm), shorthorn sculpin (Myoxocephalus scorpius (Linnaeus, 1758); PFO 54%, PN 30%), and Pacific giant octopus (Enteroctopus dofleini (Wülker, 1910); PFO 39%, PN 8%, mean weight 31 kg) in spring, and northern rock sole (Lepidopsetta polyxystra Orr and Matarese, 2000; PFO 78%, PN 47%, mean length 35 cm), Pacific cod (Gadus macrocephalus Tilesius, 1810; PFO 56%, PN 12%, mean length 62 cm), walleye pollock (PFO 44%, PN 7%, mean length 49 cm), and red Irish lord (Hemilepidotus hemilepidotus (Tilesius, 1811); PFO 11%, PN 9%) in fall. Species of Cryptacanthidae, Liparidae, and Zoarcidae were highly represented and exclusive to spring collections. Predictable seasonal concentrations and movements of mature prey along frontal boundaries of the continental shelf and ice edge may be critical to male Steller sea lion fitness during the non-breeding season.

We present a method for modeling multiple species distributions simultaneously using Dirichlet Process random effects to cluster species into guilds. Guilds are ecological groups of species that behave or react similarly to some environmental conditions. By modeling latent guild structure, we capture the cross-correlations in abundance or occurrence of species over surveys. In addition, ecological information about the community structure is obtained as a byproduct of the model. By clustering species into similar functional groups, prediction uncertainty of community structure at additional sites is reduced over treating each species separately. The method is illustrated with a small simulation demonstration, as well as an analysis of a mesopelagic fish survey from the eastern Bering Sea near Alaska. The simulation data analysis shows that guild membership can be extracted as the differences between groups become larger and if guild differences are small the model naturally collapses all the species into a small number of guilds which increases predictive efficiency by reducing the number of parameters to that which is supported by the data.

Background Circulating hematopoietic progenitor cells (PCs; CD34+ and CD34+/KDR+) facilitate neurogenesis and neovascularization, promoting increased cortical thickness and white matter integrity in animal models. However, it unknown whether low PCs are associated with trauma symptoms or neurovascular health among veterans. Objectives Determine whether lower PCs are associated with: (1) posttraumatic stress disorder (PTSD) diagnosis, duration and symptoms, (2) decreased prefrontal cortical (PFC) thickness, and (3) reduced white matter integrity, indexed by white matter hypointensities (WMH), and tracts relevant to fear processing: the Uncinate Fasciculus (UF) and Inferior Fronto-Occipital Fasciculus (IFOF). Methods 100 male and 8 female combat-exposed veterans reported PTSD symptoms (43 PTSD+) and were studied by 3T MRI, acquiring whole brain T1-weighted images and, for a subsample (n=54), diffusion tensor images. PCs were characterized by flow cytometry. Results Higher CD34+/KDR+ counts were related to greater PFC thickness (DM-PFC and DL-PFC), while higher CD34+ counts were related to better IFOF (but not UF) integrity and fewer WMH, controlling for age, gender, smoking, cardiovascular comorbidities and head injury. In PTSD+ subjects, CD34+/KDR+ counts were inversely related to time since the worst trauma, but not PTSD diagnosis or current symptoms. Conclusions PCs are associated with enhanced white matter integrity and PFC thickness, with potential implications for neurovascular plasticity and fear processing. In patients with PTSD, PCs may exhibit accelerated depletion with increasing time post-trauma.

The ecological significance of fish and squid of the mesopelagic zone (200 m-1000 m) is evident by their pervasiveness in the diets of a broad spectrum of upper pelagic predators including other fishes and squids, seabirds and marine mammals. As diel vertical migrators, mesopelagic micronekton are recognized as an important trophic link between the deep scattering layer and upper surface waters, yet fundamental aspects of the life history and energetic contribution to the food web for most are undescribed. Here, we present newly derived regression equations for 32 species of mesopelagic fish and squid based on the relationship between body size and the size of hard parts typically used to identify prey species in predator diet studies. We describe the proximate composition and energy density of 31 species collected in the eastern Bering Sea during May 1999 and 2000. Energy values are categorized by body size as a proxy for relative age and can be cross-referenced with the derived regression equations. Data are tabularized to facilitate direct application to predator diet studies and food web models.

As upper level predators in the marine ecosystem, seabirds reflect fluctuations in the marine environment that influence their prey supply. Studies of seabird diets thus provide insight into the physical and biological mechanisms that potentially drive population changes in both predators and their prey. The eastern Bering Sea shelf, among the most productive marine ecosystems in the world, has undergone significant restructuring in recent decades that is likely to continue in light of anticipated climatic change. Using a dataset spanning 35 years at two of the Pribilof Islands in the Bering Sea, we examined temporal patterns in diet and their relationships with oceanographic variables for black-legged kittiwakes (Rissa tridactyla) and thick-billed murres (Uria lomvia), two piscivorous seabirds with differing foraging strategies. Diets varied significantly among years and between islands and species. Our substantially expanded dataset supported conclusions found in previous studies of this system, including the importance of pollock, particularly age-0 class, in kittiwake diets and the absence of capelin in diets of either species since the late 1970s. Diets of both species contained more gadids at St. Paul Island and more squid and euphausiids at St. George Island, likely reflecting differences in foraging location between islands. We found some relationships between kittiwake diet and broad-scale oceanographic variables (Arctic Oscillation Index and regional summer sea surface temperature) but not with local physical variables. Almost no time series data exist on availability and abundance of zooplankton or forage fish species such as age-0 pollock, myctophids, and sandlance in the eastern Bering Sea. Our measure of diet (number of individuals within each prey type) appears too coarse for detecting complex relationships between local oceanographic variables and seabird responses, but may provide invaluable information about changes in forage fish stocks, which are frequently expensive or difficult to otherwise measure. Future diet analyses should increase emphasis on evaluating caloric input (i.e., size and nutrient composition of each prey type) as well as attempts to measure the diet of murre chicks.

Walleye pollock (Theragra chalcogramma) otoliths (n = 2,706) recovered from stomachs, small intestines, and colons of 43 northern fur seals (Callorhinus ursinus) were evaluated for size and wear by location in the digestive tract. Pollock fork length was regressed on otolith length after correction for erosion, and age was estimated from the calculated body size. Age-1+ pollock otoliths (≥6.3-mm length) were concentrated in stomachs while age-0 otoliths (≤6.2-mm length) were concentrated in colons. Less than 10% of otoliths were found in the small intestines. Pollock age decreased with progression along seal gastrointestinal tracts. Otolith quality increased along gastrointestinal tracts in numbers ≥20, which was typical of age-0 otoliths recovered from colons. Otolith distribution by age and quality along gastrointestinal tracts suggests that small (≤12 cm) schooling prey are consumed in large volume and passed as a bolus rapidly through the digestive tract before significant erosion of bony remains occurs; while larger prey are eaten in smaller volume and subjected to otolith erosion due to longer retention in the stomach. Our results illustrate the importance of multiple sampling strategies to comprehensively represent prey size in pinniped diet.

16‐17 July 2010, International AIDS Society’s Workshop “Towards a Cure”: HIV Reservoirs and Strategies to Control Them, Vienna, Austria

We explored correlation in diet trends for five piscivorous predators that reproduce on the Pribilof Islands as illustrative of the shifting structure of the Bering Sea ecosystem. We evaluated the size and species of prey consumed by adult female and juvenile northern fur seals (Callorhinus ursinus) and adults and chicks of black-legged kittiwakes (Rissa tridactyla), red-legged kittiwakes (Rissa brevirostris), thick-billed murres (Uria lomvia), and common murres (Uria aalge) from data collected between July and October 1960–2000. Sample sources included stomachs from seals and seabirds collected on pelagic foraging grounds in the eastern Bering Sea, seal scats from rookeries and seabird regurgitations and whole prey from nest sites on St. Paul and St. George Islands of the Pribilof Island archipelago. Typical prey included small fish and invertebrates (⩽20cm for seals and ⩽12cm for seabirds) that concentrate along frontal boundaries of the continental shelf/slope and in the epi-pelagic zone. Squids and fishes including walleye pollock (Theragra chalcogramma), capelin (Mallotus villosus), and sand lance (Ammodytes hexapterus) were variably important in the diet of all five predators. Some prey, such as capelin, were principal in predator diets during the 1960s (seals) and into the early 1980s (seabirds), but declined or disappeared from all predator diets thereafter while others, such as walleye pollock, occurred with increasing frequency from the 1970s forward. As the number of individuals consuming walleye pollock increased, the overall volume of pollock in seabird diets declined. This decline was coincident with a decrease in the age and body size of pollock consumed by both seabirds and fur seals. Squid and pollock were negatively correlated in the diets of their primary consumers, northern fur seals (Pearson's coefficient −0.71, p=0.016) and thick-billed murres (Pearson's coefficient=−0.74, p=0.015) from the 1970s forward. Inter-island variation in diet was evident to varying degrees for all predators, with a prevalence of fish on St. Paul Island and invertebrates on St. George Island. Bayesian time-series analysis of synthesized data described significant temporal cross-correlation in diet among northern fur seals, red- and black-legged kittiwakes, and thick-billed murres. For all correlated predators except common murres, beta-binomial modeling indicated that trends in the occurrence of four of the five primary prey (sand lance, capelin, squid, and pollock) evaluated, were significantly associated with eastern Bering Sea time-series trends in sea surface temperature, ice retreat or a combination of both. Data synthesis highlighted potential competition and a scenario for the effects of an altered prey field on the population stability of predators. The association between correlated diet changes among predators and indices of oceanographic shifts in the 1970s and the 1990s allow scrutiny of hypotheses concerning causal mechanisms in population declines.