Contributions of growth, stasis, and reproduction to fitness in brooding and broadcast spawning marine bivalves

Reproductive modes in marine invertebrates can be generally grouped into two types: those brooding larvae and those broadcast-spawning gametes into the water. We asked if these different life-history strategies differ based on how contribution to fitness is partitioned between growth, stasis, and reproduction. To investigate this question, we used published demographic data on ten diverse species of marine bivalves. We parameterized simple matrix-population models and calculated the sums of elasticities to growth, stasis, and reproduction parameters and plotted the results on triangular axes. We also assessed whether contribution patterns were correlated with reproductive mode and tropical, temperate, or polar environments. We found that some of the broadcast spawners fell in the region of the plot with high elasticities for stasis and that some of the brooders fell in the region of the plot with higher growth and reproduction elasticities than stasis ones. However, instead of a sharp dichotomy, we found a continuum in contributions of stasis parameters with long-lived brooders and short-lived broadcast spawners in the same region of the plot. There was no clear pattern of reproductive mode associated with any particular environment, but we think these preliminary results are intriguing and that further work on comparative demography of marine invertebrates is warranted. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Diversity of deep-water cetaceans in relation to temperature: implications for ocean warming

Understanding the effects of natural environmental variation on biodiversity can help predict response to future anthropogenic change. Here we analyse a large, long-term data set of sightings of deep-water cetaceans from the Atlantic, Pacific and Indian Oceans. Seasonal and geographic changes in the diversity of these genera are well predicted by a convex function of sea-surface temperature peaking at c. 21 degrees C. Thus, diversity is highest at intermediate latitudes - an emerging general pattern for the pelagic ocean. When applied to a range of Intergovernmental Panel on Climate Change global change scenarios, the predicted response is a decline of cetacean diversity across the tropics and increases at higher latitudes. This suggests that deep-water oceanic communities that dominate > 60% of the planet's surface may reorganize in response to ocean warming, with low-latitude losses of diversity and resilience.     

A noncytotoxic DsRed variant for whole-cell labeling

A common application of fluorescent proteins is to label whole cells, but many RFPs are cytotoxic when used with standard high-level expression systems. We engineered a rapidly maturing tetrameric fluorescent protein called DsRed-Express2 that has minimal cytotoxicity. DsRed-Express2 exhibits strong and stable expression in bacterial and mammalian cells, and it outperforms other available RFPs with regard to photostability and phototoxicity.     

gamma-Tocopherol nebulization by a lipid aerosolization device improves pulmonary function in sheep with burn and smoke inhalation injury

Fire accident victims who sustain both thermal injury to skin and smoke inhalation have gross evidence of systemic and pulmonary oxidant damage and acute lung injury. We hypothesized that gamma-tocopherol (gT), a reactive O(2) and N(2) scavenger, when delivered into the airway, would attenuate lung injury induced by burn and smoke inhalation. Acute lung injury was induced in chronically prepared, anesthetized sheep by 40% total burn surface area, third-degree skin burn and smoke insufflation (48 breaths of cotton smoke, <40 degrees C). The study groups were: (1) Sham (not injured, flaxseed oil (FO)-nebulized, n=6); (2) SA-neb (injured, saline-nebulized, n=6); (3) FO-neb (injured, FO-nebulized, n=6); and (4) gT+FO-neb (injured, gT and FO-nebulized, n=6). Nebulization was started 1 h postinjury, and 24 ml of FO with or without gT (51 mg/ml) was delivered into airways over 47 h using our newly developed lipid aerosolization device (droplet size: 2.5-5 microm). The burn- and smoke inhalation-induced pathological changes seen in the saline group were attenuated by FO nebulization; gT addition further improved pulmonary function. Pulmonary gT delivery along with a FO source may be a novel effective treatment strategy in management of patients with acute lung injury.     

The evolution of conformist social learning can cause population collapse in realistically variable environments

Why do societies collapse? We use an individual-based evolutionary model to show that, in environmental conditions dominated by low-frequency variation (“red noise”), extirpation may be an outcome of the evolution of cultural capacity. Previous analytical models predicted an equilibrium between individual learners and social learners, or a contingent strategy in which individuals learn socially or individually depending on the circumstances. However, in red noise environments, whose main signature is that variation is concentrated in relatively large, relatively rare excursions, individual learning may be selected from the population. If the social learning system comes to lack sufficient individual learning or cognitively costly adaptive biases, behavior ceases tracking environmental variation. Then, when the environment does change, fitness declines and the population may collapse or even be extirpated. The modeled scenario broadly fits some human population collapses and might also explain nonhuman extirpations. Varying model parameters showed that the fixation of social learning is less likely when individual learning is less costly, when the environment is less red or more variable, with larger population sizes, and when learning is not conformist or is from parents rather than from the general population. Once social learning is fixed, extirpation is likely except when social learning is biased towards successful models. Thus, the risk of population collapse may be reduced by promoting individual learning and innovation over cultural conformity, or by preferential selection of relatively fit individuals as models for social learning.     

NLRP3/Cryopyrin Is Necessary for Interleukin-1�� (IL-1��) Release in Response to Hyaluronan, an Endogenous Trigger of Inflammation in Response to Injury

Inflammation under sterile conditions is a key event in autoimmunity and following trauma. Hyaluronan, a glycosaminoglycan released from the extracellular matrix after injury, acts as an endogenous signal of trauma and can trigger chemokine release in injured tissue. Here, we investigated whether NLRP3/cryopyrin, a component of the inflammasome, participates in the inflammatory response to injury or the cytokine response to hyaluronan. Mice with a targeted deletion in cryopyrin showed a normal increase in Cxcl2 in response to sterile injuries but had decreased inflammation and release of interleukin-1β (IL-1β). Similarly, the addition of hyaluronan to macrophages derived from cryopyrin-deficient mice increased release of Cxcl2 but did not increase IL-1β release. To define the mechanism of hyaluronan-mediated activation of cryopyrin, elements of the hyaluronan recognition process were studied in detail. IL-1β release was inhibited in peritoneal macrophages derived from CD44-deficient mice, in an MH-S macrophage cell line treated with antibodies to CD44, or by inhibitors of lysosome function. The requirement for CD44 binding and hyaluronan internalization could be bypassed by intracellular administration of hyaluronan oligosaccharides (10–18-mer) in lipopolysaccharide-primed macrophages. Therefore, the action of CD44 and subsequent hyaluronan catabolism trigger the intracellular cryopyrin → IL-1β pathway. These findings support the hypothesis that hyaluronan works through IL-1β and the cryopyrin system to signal sterile inflammation.Inflammation, as defined by changes in vascular permeability and leukocyte recruitment, is an essential step for the control of microbial invasion. Specific microbial products trigger this process through a diverse array of innate immune pattern recognition receptors. However, an inflammatory response independent of infection is also an important process for maintenance of biological homeostasis. For example, normal wound healing requires a controlled inflammatory response to enable the recruitment of monocytes and the release of growth factors required for repair. This response can occur in the absence of microbial stimuli. Furthermore, inflammation and the release of proinflammatory mediators is also associated with many diseases such as rheumatoid arthritis and Crohn disease (1). These diseases are not well understood in terms of their triggers but rather are described by the subsequent release of proinflammatory mediators. Identification of the triggers of sterile inflammation represents an important goal with immediate diagnostic and therapeutic significance.Recent work has begun to elucidate pathways of inflammation that occur in the absence of microbial stimuli. Stress signals such as heat-shock proteins, intracellular components of necrotic cells not normally seen by immune cells, and components of the extracellular matrix have all been implicated as endogenous triggers of injury (2–4). Among this group is the glycosaminoglycan hyaluronan (HA),⁶ an important structural component of the extracellular matrix that is also a common component of bacterial surfaces. HA is synthesized at the cell surface and typically exists as a high molecular mass polymer greater than 10⁶ Da and composed of repeating disaccharide units of N-acetylglucosamine and glucuronic acid (5, 6). Unlike other glycosaminoglycans such as heparan sulfate or chondroitin sulfates that encode specific activity by use of a diverse disaccharide sequence, HA is not sulfated or epimerized, and only changes in HA size, concentration, and location affect function.We have previously developed murine models of sterile injury to identify the innate elements that recognize and mediate sterile inflammation (7). Our results demonstrated that (a) the initiation of a sterile intrinsic inflammatory process is dependent on TLR4 activation, (b) sterile injury induces HA accumulation at the injured site, and (c) sterile intrinsic inflammation resembles signaling events that are activated by HA. Furthermore, we have defined a novel alternative recognition complex for HA that involves TLR4, MD-2, and CD44 (7). Taken together with other work associating HA and innate pattern recognition (4, 8–10), these observations have provided new insight into mechanisms responsible for sterile inflammation.Recently, the NLR (nucleotide-binding domain and leucine rich repeat-containing) family has been extensively analyzed as a group of intracellular pattern recognition receptors (11). NLRs have a leucine-rich repeat that recognizes pathogen-associated molecular patterns including bacterial cell wall components and viral nucleic acids. NOD2 and NLR family, pyrin containing 3 (NLRP3)/cryopyrin are two of the best characterized NLRs. NOD2 recognizes the bacterial peptidoglycan-derived molecule muramyl dipeptide and activates the NF-κB pathway to induce inflammatory responses (12). Mutations of the NOD2 gene were identified in individuals with chronic inflammatory disorders such as Crohn disease (13, 14) and Blau syndrome (15). Mouse knockin mutants of NOD2, which have the same mutation in NOD2 as human patients with Crohn disease, showed elevated proinflammatory cytokines following muramyl dipeptide challenge or dextran sodium sulfate-induced bowel inflammation (16). NLRP3, also known as cyropyrin, CIAS1, NALP3, PYPAF1, forms an “inflammasome” with ASC (apoptosis-associated speck-like protein containing a CARD) and caspase-1 to convert pro-IL-1β to active IL-1β (17). Mutations in NLRP3 were identified in individuals with familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome, and neonatal onset multisystem inflammatory disease (18–20). These individuals have recurrent or chronic inflammatory symptoms, including fever, arthritis, and a urticaria-like eruption characterized by neutrophilic infiltration. In FCAS, symptoms can be elicited by cold provocation by a mechanism that appears to be mediated through the skin (15, 21).Because disorders associated with mutations in NLRP3 are examples of inflammation under sterile conditions and HA has been shown to be a trigger of sterile inflammation, we sought to further understand the mechanism of the response to HA by examining the role of cryopyrin during injury and after exposure to HA. Our results show that cryopyrin and IL-1β are integral to sterile inflammation and the response to HA. These observations provide new insight into the function of HA as a “danger signal” of injury.     

Influenza Outbreak during Sydney World Youth Day 2008: The Utility of Laboratory Testing and Case Definitions on Mass Gathering Outbreak Containment

Background

Influenza causes annual epidemics and often results in extensive outbreaks in closed communities. To minimize transmission, a range of interventions have been suggested. For these to be effective, an accurate and timely diagnosis of influenza is required. This is confirmed by a positive laboratory test result in an individual whose symptoms are consistent with a predefined clinical case definition. However, the utility of these clinical case definitions and laboratory testing in mass gathering outbreaks remains unknown.

Methods and Results

An influenza outbreak was identified during World Youth Day 2008 in Sydney. From the data collected on pilgrims presenting to a single clinic, a Markov model was developed and validated against the actual epidemic curve. Simulations were performed to examine the utility of different clinical case definitions and laboratory testing strategies for containment of influenza outbreaks. Clinical case definitions were found to have the greatest impact on averting further cases with no added benefit when combined with any laboratory test. Although nucleic acid testing (NAT) demonstrated higher utility than indirect immunofluorescence antigen or on-site point-of-care testing, this effect was lost when laboratory NAT turnaround times was included. The main benefit of laboratory confirmation was limited to identification of true influenza cases amenable to interventions such as antiviral therapy.

Conclusions

Continuous re-evaluation of case definitions and laboratory testing strategies are essential for effective management of influenza outbreaks during mass gatherings.     

Molecular Detection of Murine Herpesvirus 68 in Ticks Feeding on Free-living Reptiles

The MHV-68 (designed as Murid herpesvirus 4 (MuHV 4) strain 68) isolated from two rodents, Myodes glareolus and Apodemus flavicollis, is considered as a natural pathogen of free-living murid rodents. Recently, the detection of MHV antibodies in the blood of animals living in the same biotope as MHV-infected mice has suggested that ticks may have a role in the transmission of this pathogen. Ixodes ricinus is one the most abundant tick species in Europe known to transmit multiple pathogens causing human and animal diseases. In this study, nymphs and larvae feeding on 116 individuals of a temperate lizard species—the green lizard Lacerta viridis captured in the Slovak Karst National Park, were examined for MHV-68. The specific sequence of virion glycoprotein 150 was amplified in DNA individually isolated from I. ricinus ticks using single-copy sensitive nested polymerase chain reaction. MHV-68 was detected in ten of 649 nymphs and in five of 150 larvae, respectively. We found that 9.6% of green lizards fed at least one MHV-68-infected immature tick. Occurrence of MHV-68 within all ticks tested was 1.8%. This study is first to show that immature I. ricinus ticks feeding on free-living lizards in a Central European region could be infected with gammaherpesvirus (MHV-68), naturally infecting free-living murid rodents. Our results provide evidence supporting the hypothesis that ticks may play a mediating role in circulation of MHV-68 in nature.     

Phagocytosis, a potential mechanism for myeloid-derived suppressor cell regulation of CD8+ T cell function mediated through programmed cell death-1 and programmed cell death-1 ligand interaction

CD8(+) T cells become exhausted, inducing cell surface protein programmed cell death-1 (PD-1) as chronic virus diseases or tumors progress, but underlying mechanisms of this are unclear. We previously showed that M-CSF is important for developing tolerogenic dendritic cells (DCs) from human CD14(+) monocytes. In this article, we identify M-CSF-derived DCs (M-DCs) after stimulation with IL-10 as myeloid-derived suppressor cells with additional tolerogenic activities to CD8(+) T cells. IL-10 increased PD-1 ligand expression on M-DC, and IL-10-stimulated M-DCs (M-DC/IL-10) induced expression of PD-1 on, and apoptosis of, CD8(+) T cells and phagocytosed CD8(+) T cells. Enhanced phagocytic activity of M-DC/IL-10 required IFN-γ, which further increased PD-1 ligand and PD-2 ligand expression on M-DC/IL-10. IFN-γ-stimulated M-DC/IL-10 cells were phenotypically macrophage-like cells with little or no expression of CD86, a costimulatory molecule, but with high expression levels of CD14, CD200R, and CD80. No phagocytic activity was detected with GM-CSF-derived DCs. We propose that phagocytosis by IFN-γ-stimulated M-DC/IL-10 cells, which may be DCs or, alternatively, a unique subset of macrophages, may be a mechanism by which IFN-γ-producing CD8(+) T cells are tolerized after type 1 immune responses to chronic virus or tumor, and that IFN-γ links effector CD8(+) T cells to their phagocytic clearance.