Blubber cortisol qualitatively reflects circulating cortisol concentrations in bottlenose dolphins

Stress hormones, released into circulation as a consequence of disturbance, are classically assayed from blood samples but may also be detected in a variety of matrices. Blubber and fecal samples can be remotely collected from free‐ranging cetaceans without the confounding hormone elevations associated with chase, capture, and handling required to collect blood samples. The relationship between cortisol concentrations in circulation with that of blubber and feces, however, is unknown. To assess these associations, we elevated cortisol by orally administering hydrocortisone for five days in five bottlenose dolphins. Voluntary blood and fecal samples were collected daily; blubber biopsies were collected on day one, just prior to hydrocortisone administration, and days three and five of hydrocortisone administration. We evaluated subsequent changes in several circulating stress hormones as well as cortisol and glucocorticoid metabolites in blubber and feces, respectively. There was a significant association between cortisol levels in serum and in blubber (F_1,12.7 = 14.3, P < 0.01, mR² = 0.57) despite substantial variability in blubber cortisol levels. Counterintuitively, fecal cortisol metabolite levels were inversely related to serum cortisol. The relationship between serum and blubber cortisol levels suggests blubber samples from remote sampling may be useful to detect stress loads in this species.     

Terrigenous sediment-dominated reef platform infilling: an unexpected precursor to reef island formation and a test of the reef platform size–island age model in the Pacific

Low-lying coral reef islands are considered highly vulnerable to climate change, necessitating an improved understanding of when and why they form, and how the timing of formation varies within and among regions. Several testable models have been proposed that explain inter-regional variability as a function of sea-level history and, more recently, a reef platform size model has been proposed from the Maldives (central Indian Ocean) to explain intra-regional (intra-atoll) variability. Here we present chronostratigraphic data from Pipon Island, northern Great Barrier Reef (GBR), enabling us to test the applicability of existing regional island evolution models, and the platform size control hypothesis in a Pacific context. We show that reef platform infilling occurred rapidly (~4–5 mm yr⁻¹) under a “bucket-fill” type scenario. Unusually, this infilling was dominated by terrigenous sedimentation, with platform filling and subsequent reef flat formation complete by ~5000 calibrated years BP (cal BP). Reef flat exposure as sea levels slowly fell post highstand facilitated a shift towards intertidal and subaerial-dominated sedimentation. Our data suggest, however, a lag of ~1500 yr before island initiation (at ~3200 cal BP), i.e. later than that reported from smaller and more evolutionarily mature reef platforms in the region. Our data thus support: (1) the hypothesis that platform size acts to influence the timing of platform filling and subsequent island development at intra-regional scales; and (2) the hypothesis that the low wooded islands of the northern GBR conform to a model of island formation above an elevated reef flat under falling sea levels.

     

Expression and function of T cell homing molecules in Hodgkin’s lymphoma

Circulating T lymphocytes enter a tissue if they express appropriate chemokine receptors and adhesion molecules to engage ligands presented at this site. To aid rational development of T cell-based therapies for Hodgkin's lymphoma (HL), we have assessed the expression and function of homing receptors on tumour-infiltrating T cells in HL and compared them with T cells from unaffected lymph nodes and colorectal cancer tissue. Chemokine receptors CXCR3, CXCR4 and CCR7 were expressed on a large proportion of T cells within HL tissue and mediated chemotaxis to purified chemokine. The corresponding ligands (CXCL10, CXCL12, CCL21) were expressed on the malignant cells and/or vascular endothelium. Adhesion molecules including CD62L were widely expressed on HL-derived T cells and their corresponding ligands were detected on vessels within the tumour. This homing phenotype was distinct from T cells isolated from colorectal cancer, but matched closely the phenotype of T cells from unaffected lymph nodes. Thus, T cell recruitment to HL resembles entry of na?ve/central memory T cells into normal lymph nodes. This has important implications for current approaches to treat HL using T cells activated and expanded in vitro that lack CCR7 and CD62L expression.     

Viral Persistence and Chronic Immunopathology in the Adult Central Nervous System following Coxsackievirus Infection during the Neonatal Period

Coxsackieviruses are significant human pathogens, and the neonatal central nervous system (CNS) is a major target for infection. Despite the extreme susceptibility of newborn infants to coxsackievirus infection and viral tropism for the CNS, few studies have been aimed at determining the long-term consequences of infection on the developing CNS. We previously described a neonatal mouse model of coxsackievirus B3 (CVB3) infection and determined that proliferating stem cells in the CNS were preferentially targeted. Here, we describe later stages of infection, the ensuing inflammatory response, and subsequent lesions which remain in the adult CNS of surviving animals. High levels of type I interferons and chemokines (in particular MCP-5, IP10, and RANTES) were upregulated following infection and remained at high levels up to day 10 postinfection (p.i). Chronic inflammation and lesions were observed in the hippocampus and cortex of surviving mice for up to 9 months p.i. CVB3 RNA was detected in the CNS up to 3 months p.i at high abundance (∼10⁶ genomes/mouse brain), and viral genomic material remained detectable in culture after two rounds of in vitro passage. These data suggest that CVB3 may persist in the CNS as a low-level, noncytolytic infection, causing ongoing inflammatory lesions. Thus, the effects of a relatively common infection during the neonatal period may be long lasting, and the prognosis for newborn infants recovering from acute infection should be reexplored.Early damaging events on the central nervous system (CNS) by infection can result not only in severe physical and intellectual disability but also in less obvious neurological deficits. For example, children who were thought to have fully recovered from neonatal CNS virus infections exhibited some deficiency in scholastic performance (12). Thus, the enduring harmful effects of childhood infections on the CNS may be greatly underappreciated. Picornaviruses including polioviruses, coxsackieviruses, and other unclassified enteroviruses frequently infect the CNS (60). Although these infections often are considered acute and self-limiting, evidence is emerging that these viruses—or at least the viral RNAs—may persist for months or years after the initial infection. For example, ∼50 years after the primary infection, a large percentage (∼30%) of polio victims are now experiencing new symptoms (postpolio syndrome), which some investigators have correlated with the presence of viral RNA in the CNS (43). Worldwide distribution of enterovirus infection is revealed by the detection of enterovirus-specific antibodies in the serum of approximately 75% of individuals within developed countries. For example, in 1996, approximately 10 to 15 million diagnosed cases of enterovirus infection occurred in the United States alone (49). Few studies have been done to determine if enteroviruses, or their close relatives, have the ability to persist and cause long-term damage in the CNS (10, 56) or whether previous infection of neurons may indirectly lead to the degeneration of aging motor neurons.Coxsackievirus, a member of the enterovirus genus, is a fairly frequent childhood infection and may cause severe morbidity and mortality in humans, predominantly in the very young. Infants infected with coxsackievirus have been shown to be extremely susceptible to meningitis and encephalitis. Severe demyelinating diseases may occur following infection, including acute disseminated encephalomyelitis (18) and acute transverse myelitis (27). Also, a number of delayed neuropathologies have been associated with previous coxsackievirus infection, including schizophrenia (47, 52), encephalitis lethargica (16), and amyotrophic lateral sclerosis (62, 63). If human neurotropic viruses persist, they could provide a chronic inflammatory stimulus, leading to regional cytokine induction and activation of autoreactive T cells through molecular mimicry and bystander activation (32, 45). This may be especially true for viruses, such as coxsackievirus, which have the ability to infect stem cells (24) and neurons (1). Recently, we have shown that coxsackievirus B3 (CVB3) targets proliferating cells in regions of the neonatal CNS supporting neurogenesis (24). Nonetheless, infected migratory neuronal progenitor cells were able to differentiate into mature neurons. Many neurons eventually underwent caspase-3-mediated apoptosis at later stages of disease (22).Intriguingly, viral RNA was detected in the CNS of surviving pups in the absence of infectious virus for up to 30 days postinfection (p.i.). The detection of CVB3 RNA in target tissues may have great significance for CVB3-mediated disease, given that the long-term presence of replication-restricted CVB3 RNA in the heart (generated using transgenic techniques) has been directly associated with dilated cardiomyopathy in a previous study by Wessely et al. (59). We were therefore interested in expanding this notable observation in the CNS by significantly increasing the number of animals examined, more precisely quantifying the amounts of viral RNA, and determining how long viral RNA might persist in the CNS. In addition, we thoroughly assessed the nature and degree of neuropathology in surviving animals harboring CVB3 RNA. These studies may help predict the lasting neurological sequelae of a previous viral infection on the developing host.     

Location of Trp265 in metarhodopsin II: implications for the activation mechanism of the visual receptor rhodopsin

Isomerization of the 11-cis retinal chromophore in the visual pigment rhodopsin is coupled to motion of transmembrane helix H6 and receptor activation. We present solid-state magic angle spinning NMR measurements of rhodopsin and the metarhodopsin II intermediate that support the proposal that interaction of Trp265(6.48) with the retinal chromophore is responsible for stabilizing an inactive conformation in the dark, and that motion of the beta-ionone ring allows Trp265(6.48) and transmembrane helix H6 to adopt active conformations in the light. Two-dimensional dipolar-assisted rotational resonance NMR measurements are made between the C19 and C20-methyl groups of the retinal and uniformly 13C-labeled Trp265(6.48). The retinal C20-Trp265(6.48) contact present in the dark-state of rhodopsin is lost in metarhodopsin II, and a new contact is formed with the C19 methyl group. We have previously shown that the retinal translates 4-5 A toward H5 in metarhodopsin II. This motion, in conjunction with the Trp-C19 contact, implies that the Trp265(6.48) side-chain moves significantly upon rhodopsin activation. NMR measurements also show that a packing interaction in rhodopsin between Trp265(6.48) and Gly121(3.36) is lost in metarhodopsin II, consistent with H6 motion away from H3. However, a close contact between Gly120(3.35) on H3 and Met86(2.53) on H2 is observed in both rhodopsin and metarhodopsin II, suggesting that H3 does not change orientation significantly upon receptor activation.     

Regional assessment of emerald ash borer, <Emphasis Type="Italic">Agrilus planipennis</Emphasis>, impacts in forests of the Eastern United States

Native to Asia, the emerald ash borer (Agrilus planipennis Fairmaire) has caused extensive mortality of ash tree species (Fraxinus spp.) in the eastern United States. As of 2013, the pest was documented in 18 % of counties within the natural range of ash in the eastern United States. Regional forest inventory data from the U.S. Forest Service Forest Inventory and Analysis program were used to quantify trends in ash mortality rate and volume per hectare relative to the year of initial emerald ash borer detection. Results indicate that the annual ash mortality rate increases by as much as 2.7 % per year after initial detection of the pest in a county. Corresponding decreases in ash volume (as much as 1.8 m³ per hectare per year) continue for several more years until most live ash is killed. These results, while not necessarily representative of the effects on ash in urban ecosystems, document the severe impact this invading herbivore is having on forests as it expands its range in North America.     

Group B Streptococcus Engages an Inhibitory Siglec through Sialic Acid Mimicry to Blunt Innate Immune and Inflammatory Responses In Vivo

Group B Streptococcus (GBS) is a common agent of bacterial sepsis and meningitis in newborns. The GBS surface capsule contains sialic acids (Sia) that engage Sia-binding immunoglobulin-like lectins (Siglecs) on leukocytes. Here we use mice lacking Siglec-E, an inhibitory Siglec of myelomonocytic cells, to study the significance of GBS Siglec engagement during in vivo infection. We found GBS bound to Siglec-E in a Sia-specific fashion to blunt NF-κB and MAPK activation. As a consequence, Siglec-E-deficient macrophages had enhanced pro-inflammatory cytokine secretion, phagocytosis and bactericidal activity against the pathogen. Following pulmonary or low-dose intravenous GBS challenge, Siglec-E KO mice produced more pro-inflammatory cytokines and exhibited reduced GBS invasion of the central nervous system. In contrast, upon high dose lethal challenges, cytokine storm in Siglec-E KO mice was associated with accelerated mortality. We conclude that GBS Sia mimicry influences host innate immune and inflammatory responses in vivo through engagement of an inhibitory Siglec, with the ultimate outcome of the host response varying depending upon the site, stage and magnitude of infection.     

Effects of Age,Adipose Percent,and Reproduction on PCB Concentrations and Profiles in an Extreme Fasting North Pacific Marine Mammal

Persistent organic pollutants, including polychlorinated biphenyls (PCBs), are widely distributed and detectable far from anthropogenic sources. Northern elephant seals (Mirounga angustirostris) biannually travel thousands of kilometers to forage in coastal and open-ocean regions of the northeast Pacific Ocean and then return to land where they fast while breeding and molting. Our study examined potential effects of age, adipose percent, and the difference between the breeding and molting fasts on PCB concentrations and congener profiles in blubber and serum of northern elephant seal females. Between 2005 and 2007, we sampled blubber and blood from 58 seals before and after a foraging trip, which were then analyzed for PCBs. Age did not significantly affect total PCB concentrations; however, the proportion of PCB congeners with different numbers of chlorine atoms was significantly affected by age, especially in the outer blubber. Younger adult females had a significantly greater proportion of low-chlorinated PCBs (tri-, tetra-, and penta-CBs) than older females, with the opposite trend observed for hepta-CBs, indicating that an age-associated process such as parity (birth) may significantly affect congener profiles. The percent of adipose tissue had a significant relationship with inner blubber PCB concentrations, with the highest mean concentrations observed at the end of the molting fast. These results highlight the importance of sampling across the entire blubber layer when assessing contaminant levels in phocid seals and taking into account the adipose stores and reproductive status of an animal when conducting contaminant research.