Inhaled endotoxin induces an inflammatory response that contributes to the development and severity of asthma and other forms of airway disease. Here, we show that inhaled endotoxin-induced acute bronchoconstriction, TNF, IL-12p40, and KC production, protein leak, and neutrophil recruitment in the lung are abrogated in mice deficient for the adaptor molecule MyD88. Bronchoconstriction, inflammation, and protein leak are normal in Toll/IL-1R domain-containing adaptor inducing IFN-beta-deficient mice. MyD88 is involved in TLR, but also in IL-1R-associated kinase 1-mediated IL-1R and -18R signaling. We exclude a role for IL-1 and IL-18 pathways in this response, as IL-1R1 and caspase-1 (ICE)-deficient mice develop lung inflammation while TLR4-deficient mice are unresponsive to inhaled LPS. Significantly, using bone marrow chimera, we demonstrate that both hemopoietic and resident cells are necessary for a full MyD88-dependent response to inhaled endotoxin; bronchoconstriction depends on resident cells while cytokine secretion is mediated by hemopoietic cells.

1. Fifteen species richness estimators (three asymptotic based on species accumulation curves, 11 nonparametric, and one based in the species-area relationship) were compared by examining their performance in estimating the total species richness of epigean arthropods in the Azorean Laurisilva forests. Data obtained with standardized sampling of 78 transects in natural forest remnants of five islands were aggregated in seven different grains (i.e. ways of defining a single sample): islands, natural areas, transects, pairs of traps, traps, database records and individuals to assess the effect of using different sampling units on species richness estimations. 2. Estimated species richness scores depended both on the estimator considered and on the grain size used to aggregate data. However, several estimators (ACE, Chao 1, Jackknifel and 2 and Bootstrap) were precise in spite of grain variations. Weibull and several recent estimators [proposed by Rosenzweig et al. (Conservation Biology, 2003, 17, 864-874), and Ugland et al. (Journal of Animal Ecology, 2003, 72, 888-897)] performed poorly. 3. Estimations developed using the smaller grain sizes (pair of traps, traps, records and individuals) presented similar scores in a number of estimators (the above-mentioned plus ICE, Chao2, Michaelis-Menten, Negative Exponential and Clench). The estimations from those four sample sizes were also highly correlated. 4. Contrary to other studies, we conclude that most species richness estimators may be useful in biodiversity studies. Owing to their inherent formulas, several nonparametric and asymptotic estimators present insensitivity to differences in the way the samples are aggregated. Thus, they could be used to compare species richness scores obtained from different sampling strategies. Our results also point out that species richness estimations coming from small grain sizes can be directly compared and other estimators could give more precise results in those cases. We propose a decision framework based on our results and on the literature to assess which estimator should be used to compare species richness scores of different sites, depending on the grain size of the original data, and of the kind of data available (species occurrence or abundance data).

A group of strains with potent extracellular enzymic activity were isolated from the surfaces of the chain-forming sea-ice diatom Melosira and from an unidentified macrophyte collected from the Eastern Antarctic coastal zone. 16S rDNA sequence analysis indicated that the strains belonged to the genus Cellulophaga and showed greatest similarity to the species Cellulophaga baltica (sequence similarity 97%). Phenotypic characteristics, DNA base composition and DNA-DNA hybridization values clearly separate the Antarctic strains from Cellulophaga baltica and other Cellulophaga species. Thus, the strains form a distinct and novel species and have the proposed name Cellulophaga algicola sp. nov. (type strain IC166T = ACAM 630T). In addition, it was recognized that the species Cytophaga uliginosa (ZoBell and Upham 1944) Reichenbach 1989, a species phylogenetically remote from the type species of the genus Cytophaga, possessed 16S rDNA sequences and phenotypic and chemotaxonomic traits similar to those of other Cellulophaga species. Thus, it was proposed that the species Cytophaga uliginosa be renamed as Cellulophaga uliginosa comb. nov.

1) Three indices of global climate have been monitored in the record of the past 450,000 years in Southern Hemisphere ocean-floor sediments. 2) Over the frequency range 10(-4) to 10(-5) cycle per year, climatic variance of these records is concentrated in three discrete spectral peaks at periods of 23,000, 42,000, and approximately 100,000 years. These peaks correspond to the dominant periods of the earth's solar orbit, and contain respectively about 10, 25, and 50 percent of the climatic variance. 3) The 42,000-year climatic component has the same period as variations in the obliquity of the earth's axis and retains a constant phase relationship with it. 4) The 23,000-year portion of the variance displays the same periods (about 23,000 and 19,000 years) as the quasi-periodic precession index. 5) The dominant, 100,000-year climatic [See table in the PDF file] component has an average period close to, and is in phase with, orbital eccentricity. Unlike the correlations between climate and the higher-frequency orbital variations (which can be explained on the assumption that the climate system responds linearly to orbital forcing), an explanation of the correlation between climate and eccentricity probably requires an assumption of nonlinearity. 6) It is concluded that changes in the earth's orbital geometry are the fundamental cause of the succession of Quaternary ice ages. 7) A model of future climate based on the observed orbital-climate relationships, but ignoring anthropogenic effects, predicts that the long-term trend over the next sevem thousand years is toward extensive Northern Hemisphere glaciation.

Human immunodeficiency syndrome (HIV) infection leads to a progressive loss of T-cell-mediated immunity associated with T-cell apoptosis. We report here that CD4+ and CD8+ T cells from HIV-1-infected persons are sensitive to Fas (CD95/APO-1)-mediated death induced either by an agonistic anti-Fas antibody or by the physiologic soluble Fas ligand, although showing no sensitivity to tumor necrosis factor alpha-induced death. CD4+ and CD8+ T-cell apoptosis induced by Fas ligation was enhanced by inhibitors of protein synthesis and was prevented either by a soluble Fas receptor decoy or an antagonistic anti-Fas antibody. Fas-mediated apoptosis could also be prevented in a CD4+ or CD8+ T-cell-type manner (1) by several protease antagonists, suggesting the involvement of the interleukin-1beta (IL-1beta)-converting enzyme (ICE)-related cysteine protease in CD4+ T-cell death and of both a CPP32-related cysteine protease and a calpain protease in CD8+ T-cell death; and (2) by three cytokines, IL-2, IL-12, and IL-10, that exerted their effects through a mechanism that required de novo protein synthesis. Finally, T-cell receptor (TCR)-induced apoptosis of CD4+ T cells from HIV-infected persons involved a Fas-mediated death process, whereas TCR stimulation of CD8+ T cells led to a different Fas-independent death process. These findings suggest that Fas-mediated T-cell death is involved in acquired immunodeficiency syndrome (AIDS) pathogenesis and that modulation of Fas-mediated signaling may represent a target for new therapeutic strategies aimed at the prevention of CD4+ T-cell death in AIDS.

Variations in ocean-atmosphere coupling over time in the Southern Ocean have dominant effects on sea-ice extent and ecosystem structure, but the ultimate consequences of such environmental changes for large marine predators cannot be accurately predicted because of the absence of long-term data series on key demographic parameters. Here, we use the longest time series available on demographic parameters of an Antarctic large predator breeding on fast ice and relying on food resources from the Southern Ocean. We show that over the past 50 years, the population of emperor penguins (Aptenodytes forsteri) in Terre Adélie has declined by 50% because of a decrease in adult survival during the late 1970s. At this time there was a prolonged abnormally warm period with reduced sea-ice extent. Mortality rates increased when warm sea-surface temperatures occurred in the foraging area and when annual sea-ice extent was reduced, and were higher for males than for females. In contrast with survival, emperor penguins hatched fewer eggs when winter sea-ice was extended. These results indicate strong and contrasting effects of large-scale oceanographic processes and sea-ice extent on the demography of emperor penguins, and their potential high susceptibility to climate change.

A principal limitation of cryo-transmission electron microscopy performed on cells or tissues is the accessible specimen thickness. This is exacerbated in tomography applications, where the aspect ratio (and thus the apparent specimen thickness) changes considerably during specimen tilting. Cryo-ultramicrotomy is the most obvious way of dealing with this problem; however, frozen-hydrated sections suffer from potentially inconsistent compression that cannot be corrected with certainty, and furthermore, yields of sections that satisfy all of the conditions necessary for tomographic imaging are poor. An alternative approach that avoids mechanical deformations is the use of focused ion beam (FIB) instrumentation, where thinning of the frozen-hydrated specimen occurs through the process of sputtering with heavy ions, typically gallium. Here, we use correlative cryo-fluorescence microscopy to navigate large cellular volumes and to localize specific cellular targets. We show that the selected targets in frozen-hydrated specimens can be accessed directly by focused ion beam milling. We also introduce a novel cryo-planing procedure as a method that could facilitate thinning of large areas of vitreous ice prior to cryo-fluorescence, FIB thinning, and cryo-electron tomography.

The serine protease granzyme B, which is secreted by cytotoxic cells, is one of the major effectors of apoptosis in susceptible targets. To examine the apoptotic mechanism of granzyme B, we have analyzed its effect on purified proteins that are thought to be components of death pathways inherent to cells. We demonstrate that granzyme B processes interleukin 1beta-converting enzyme (ICE) and the ICE-related protease Yama (also known as CPP32 or apopain) by limited proteolysis. Processing of ICE does not lead to activation. However, processing by granzyme B leads directly to the activation of Yama, which is now able to bind inhibitors and cleave the substrate poly(ADP-ribose) polymerase whose proteolysis is a marker of apoptosis initiated by several other stimuli. Thus ICE-related proteases can be activated by serine proteases that possess the correct specificity. Activation of pro-Yama by granzyme B is within the physiologic range. Thus the cytotoxic effect of granzyme B can be explained by its activation of an endogenous protease component of a programmed cell death pathway.

Cysteine proteases of the ICE/CED-3 family (caspases) are required for the execution of programmed cell death (PCD) in a wide range of multicellular organisms. Caspases are implicated in the execution of apoptosis in Drosophila melanogaster by the observation that expression of baculovirus p35, a caspase inhibitor, blocks cell death in vivo in Drosophila. We report here the identification and characterization of drICE, a D. melanogaster caspase. We show that overexpression of drICE sensitizes Drosophila cells to apoptotic stimuli and that expression of an N-terminally truncated form of drICE rapidly induces apoptosis in Drosophila cells. Induction of apoptosis by rpr overexpression or by cycloheximide or etoposide treatment of Drosophila cells results in proteolytic processing of drICE. We further show that drICE is a cysteine protease that cleaves baculovirus p35 and Drosophila lamin DmO in vitro and that drICE is expressed at all the stages of Drosophila development at which PCD can be induced. Taken together, these results strongly argue that drICE is an apoptotic caspase that acts downstream of rpr. drICE is therefore the first unequivocal link between the molecular machinery of Drosophila cell death and the conserved machinery of Caenorhabditis elegans and vertebrates. Identification of drICE should facilitate the elucidation of upstream regulators and downstream targets of caspases by genetic screening.

BACKGROUND

In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte, the precursor form of interleukin 1 beta (IL-1 beta, 31 kD) is processed by IL-1 beta converting enzyme (ICE) to the mature, bioactive form (17 kD). IL-1 beta is a proinflammatory cytokine which is likely to have a role in the pathogenesis of inflammatory bowel disease (IBD).

OBJECTIVE

To investigate the expression and processing of IL-1 beta and ICE by tissue macrophages from normal and IBD colonic mucosa.

METHODS

Mucosal biopsy specimens and lamina propria cells from normal and IBD colons were studied by reverse transcription polymerase chain reaction (RT-PCR), western blot analysis, and ELISA (enzyme linked immunosorbent assay).

RESULTS

Normal colonic macrophages synthesised only the precursor form of IL-1 beta whereas in IBD the mature form was also produced. Similarly, cells from normal colonic mucosa synthesised ICE as the precursor (p45) only, whereas macrophages from IBD colons produced active (p20) ICE. Ac-Tyr-Val-Ala-Asp-CHO, a specific peptide aldehyde inhibitor of ICE, significantly reduced the amount of mature IL-1 beta released by isolated IBD macrophages (from a median of 1.2 (range 0.78-4.42) ng/ml to 0.43 (0.21-1.6) ng/ml; p < 0.01).

CONCLUSIONS

Exposure of normal colonic macrophages to LPS only induces the production of the precursor form of IL-1 beta, because the cells fail to activate ICE. In contrast, IBD colonic macrophages are able to activate ICE and hence release mature IL-1 beta in a manner similar to circulating monocytes. This is consistent with IBD macrophages being recently recruited from the circulating monocyte population. Targeted inhibition of ICE may represent a novel form of therapy in IBD.

An approximately 5000-year-old mummified human body was recently found in the Tyrolean Alps. The DNA from tissue samples of this Late Neolithic individual, the so-called "Ice Man," has been extracted and analyzed. The number of DNA molecules surviving in the tissue was on the order of 10 genome equivalents per gram of tissue, which meant the only multi-copy sequences could be analyzed. The degradation of the DNA made the enzymatic amplification of mitochondrial DNA fragments of more than 100 to 200 base pairs difficult. One DNA sequence of a hypervariable segment of the mitochondrial control region was determined independently in two different laboratories from internal samples of the body. This sequence showed that the mitochondrial type of the Ice Man fits into the genetic variation of contemporary Europeans and that it was most closely related to mitochondrial types determined from central and northern European populations.

We have used electron microscopy to examine the two major conformational states of the helical filament formed by the RecA protein of Escherichia coli. The compressed filament, formed in the absence of a nucleotide cofactor either as a self-polymer or on a single-stranded DNA molecule, is characterized in solution by about 6.1 subunits per turn of a 76 A pitch helix, and appears to be inactive with respect to all RecA activity. The active state of the filament, formed with ATP or an ATP analog on either a single or double-stranded DNA substrate, has about 6.2 subunits per turn of a 94 A pitch helix. Measurements of the contour length of RecA-covered single-stranded DNA circles in ice, formed in the absence of nucleotide cofactor, indicate that each RecA subunit binds five bases, in contrast to the three bases or base-pairs per subunit in the active state. The different stoichiometries of DNA binding suggests that the two polymeric forms are not interconvertible, as has been suggested on biochemical grounds. A three-dimensional reconstruction of the inactive state shows the same general features as the 83 A pitch filament present in the RecA crystal. This structural similarity and the fact that the crystal does not contain ATP or DNA suggests that the crystal structure is more similar to the compressed filament than the active, extended filament.

Apoptosis (programmed cell death) is a fundamental process for normal development of multicellular organisms, and is involved in the regulation of the immune system, normal morphogenesis, and maintenance of homeostasis, ICE/CED-3 family cysteine proteases have been implicated directly in apoptosis, but relatively few of the substrates through which their action is mediated have been identified. Here we report that D4-GDI, an abundant hematopoietic cell GDP dissociation inhibitor for the Ras-related Rho family GTPases, is a substrate of the apoptosis protease CPP32/Yama/Apopain. D4-GDI was rapidly truncated to a 23-kDa fragment in Jurkat cells with kinetics that parallel the onset of apoptosis following Fas cross-linking with agonistic antibody or treatment with staurosporine. Fas- and staurosporine-induced apoptosis as well as cleavage of D4-GDI were inhibited by the ICE inhibitor, YVAD-cmk. D4-GDI was cleaved in vitro by recombinant CPP32 expressed in Escherichia coli to form a 23-kDa fragment. The CPP32-mediated cleavage of D4-GDI was completely inhibited by 1 microM DEVD-CHO, a reported selective inhibitor of CPP32. In contrast, the ICE-selective inhibitors, YVAD-CHO or YVAD-cmk, did not inhibit CPP32-mediated D4-GDI cleavage at concentrations up to 50 microM. N-terminal sequencing of the 23-kDa D4-GDI fragment demonstrated that D4-GDI was cleaved between Asp19 and Ser20 of the poly(ADP-ribose) polymerase-like cleavage sequence DELD19S. These data suggest that regulation by D4-GDI of Rho family GTPases may be disrupted during apoptosis by CPP32-mediated cleavage of the GDI protein.

Two studies investigated factors that promote the desire for food when people are not energy depleted. In Study 1, 20 male and female subjects, tested under conditions of either hunger or satiety, were exposed to one of two palatable foods (pizza or ice cream) and then given more of that food to eat. Operationally-satiated subjects still ate pizza or ice cream, and the sight of these foods enhanced reported desire for them. The amount of these foods consumed was predicted by the subjects' self-reported desire for the food. In Study 2, 28 male subjects were fed to satiety, then primed with either pizza or ice cream (or not primed at all) and then given both pizza and ice cream to eat. Results showed that a brief taste of a desirable food enhanced its intake relative to the other, equally-preferred food. The data are discussed in the context of the effects of priming as a form of appetite whetting. Also, it is suggested that our operations for eliciting stimulus-induced eating in sated subjects may be useful for future examinations of the psychological properties of craving.

Global climate and the atmospheric partial pressure of carbon dioxide () are correlated over recent glacial cycles, with lower during ice ages, but the causes of the changes are unknown. The modern Southern Ocean releases deeply sequestered CO(2) to the atmosphere. Growing evidence suggests that the Southern Ocean CO(2) 'leak' was stemmed during ice ages, increasing ocean CO(2) storage. Such a change would also have made the global ocean more alkaline, driving additional ocean CO(2) uptake. This explanation for lower ice-age , if correct, has much to teach us about the controls on current ocean processes.

The role of flagellar motility in determining the epiphytic fitness of an ice-nucleation-active strain of Pseudomonas syringae was examined. The loss of flagellar motility reduced the epiphytic fitness of a normally motile P. syringae strain as measured by its growth, survival, and competitive ability on bean leaf surfaces. Equal population sizes of motile parental or nonmotile mutant P. syringae strains were maintained on bean plants for at least 5 days following the inoculation of fully expanded primary leaves. However, when bean seedlings were inoculated before the primary leaves had expanded and bacterial populations on these leaves were quantified at full expansion, the population size of the nonmotile derivative strain reached only 0.9% that of either the motile parental or revertant strain. When fully expanded bean primary leaves were coinoculated with equal numbers of motile and nonmotile cells, the population size of a nonmotile derivative strain was one-third of that of the motile parental or revertant strain after 8 days. Motile and nonmotile cells were exposed in vitro and on plants to UV radiation and desiccating conditions. The motile and nonmotile strains exhibited equal resistance to both stresses in vitro. However, the population size of a nonmotile strain on leaves was less than 20% that of a motile revertant strain when sampled immediately after UV irradiation. Epiphytic populations of both motile and nonmotile P. syringae declined under desiccating conditions on plants, and after 8 days, the population size of a nonmotile strain was less than one-third that of the motile parental or revertant strain.

Among intracranial germ cell tumors, nongerminomatous tumors have proved refractory to conventional treatment with surgery and irradiation. The median survival is less than 2 years. Since 1983, chemotherapy has been delivered in Japan as an adjuvant therapy in patients with intracranial nongerminomatous germ cell tumors. Based on our clinical experience, we undertook a multi-institutional phase II study to establish post-surgical combined chemotherapy and radiation therapy for primary germ cell tumors in the brain. We adopted carboplatin-etoposide (CARB-VP) or cisplatin-etoposide (PE) combination chemotherapy for patients with germinomas and those with tumors that placed them in the intermediate prognosis group, and ifosphamide-cisplatin-etoposide (ICE) for patients with tumors that placed them in the poor prognosis group. One hundred and twelve patients were evaluated. Among patients with germinoma (n = 75), the rate or complete remission after combination therapy was 92.0%; it was 67.8% for patients in the intermediate prognosis group (n = 28). Tumor recurrence was noted in 9 patients with germinoma and 2 patients in the intermediate prognosis group. Of 9 patients with a poor prognosis, 4 experienced disease progression during treatment and died within 10 months. There were no serious complications attributable to the combination therapy. Our treatment protocols are effective for patients with germinomas and those with an intermediate prognosis.

OBJECTIVE

This study reports the incidence of, risk factors for, and management of left atrial (LA) thrombus documented by intracardiac echocardiography (ICE) during LA ablation for atrial fibrillation (AF).

BACKGROUND

Thrombus formation is a risk associated with LA ablation procedures.

METHODS

Intracardiac echocardiography imaging was performed in 232 patients (184 men, average age 55 +/- 11 years) with AF undergoing pulmonary vein ostial ablation.

RESULTS

Anticoagulation (activated clotting time >250 s) was maintained after dual transseptal catheterization. Left atrial thrombus (n = 30) was observed in 24 of 232 patients (10.3%). Thrombi measured 12.9 +/- 11.1 mm (length) and 2.2 +/- 1.3 mm (width) and were attached to a sheath or mapping catheter. Most thrombi (27 of 30, 90%) were eliminated from the LA by withdrawal of the sheath and catheter into the right atrium (RA). Two thrombi became wedged in the interatrial septum and incompletely withdrawn into the RA, and one was recognized only on post-procedure review of ICE images. Patients with LA thrombus had an increased LA diameter (4.8 +/- 0.5 vs. 4.5 +/- 0.6 cm, p < 0.02), spontaneous echo contrast (67% vs. 3%, p < 0.0001) and a history of persistent AF (29% vs. 6%, p < 0.0002). Multivariate discriminant analysis showed that spontaneous echo contrast (f = 97.9, p < 0.0001) was the most important determinant of LA thrombus formation. No patient with LA thrombus suffered a clinical thromboembolic complication.

CONCLUSIONS

Left atrial thrombus identified on ICE may occur during LA catheter ablation procedures despite aggressive anticoagulation. Spontaneous echo contrast may predict risk for LA thrombus formation. Left atrial thrombus may be successfully withdrawn into the RA under ICE imaging with no overt complications.

U.S. immigrants have faced a changing landscape with regard to immigration enforcement over the last two decades. Following the passage of the Illegal Immigration Reform and Immigrant Responsibility Act of 1996, and the creation of the Immigration and Customs Enforcement (ICE) agency after the attacks of September 11, 2001, detention and deportation activity increased substantially. As a result, immigrants today are experiencing heightened fear of profiling and deportation. Little research exists on how these activities affect the health and well-being of U.S. immigrant communities. This study sought to address this gap by using community-based participatory research to investigate the impact of enhanced immigration enforcement on immigrant health in Everett, Massachusetts, USA, a city with a large and diverse immigrant population. Community partners and researchers conducted 6 focus groups with 52 immigrant participants (documented and undocumented) in five languages in May 2009. The major themes across the groups included: 1) Fear of deportation, 2) Fear of collaboration between local law enforcement and ICE and perception of arbitrariness on the part of the former and 3) Concerns about not being able to furnish documentation required to apply for insurance and for health care. Documented and undocumented immigrants reported high levels of stress due to deportation fear, which affected their emotional well-being and their access to health services. Recommendations from the focus groups included improving relationships between immigrants and local police, educating immigrants on their rights and responsibilities as residents, and holding sessions to improve civic engagement. Immigration enforcement activities and the resulting deportation fear are contextual factors that undermine trust in community institutions and social capital, with implications for health and effective integration processes. These factors should be considered by any community seeking to improve the integration process.

OBJECTIVE

Increased basal cortisol levels have been found in bulimia nervosa. After stress, increased cortisol levels have been associated with increased food intake in healthy women. Therefore, we assessed cortisol, hunger, and desire to binge eat after a cold pressor test (CPT) among women with binge eating disorder (BED).

METHODS

Twenty-two obese (body mass index [BMI] = 36.7 +/- 6.5 SD) females (11 non-BED, 11 BED) completed the Zung depression scale and underwent the CPT, hand submerged in ice water for 2 minutes. Over 60 minutes, periodic ratings of hunger and desire to binge eat were obtained, just before blood draws for cortisol, as well as insulin. On a separate day, participants had a 1-mg oral dexamethasone suppression test (DST).

RESULTS

The BED group had higher depression scores than the non-BED (p = .04), but depression was not a significant covariate for the cortisol response or to DST. After controlling for contraceptive use (n = 3), the BED group had higher basal cortisol than the non-BED group (p = .03), but cortisol did not differ after DST (p = .40). The BED group had nearly significant greater cortisol AUC after the CPT (p = .057) after controlling for insulin AUC and contraceptive use (p = .057). The BED group also had greater AUC for hunger (p = .03) and desire to binge eat (p = .02) after the CPT.

CONCLUSIONS

These findings support our hypothesis of a hyperactive HPA-axis in BED, which may contribute to greater hunger and binge eating.

We report here the identification and functional characterization of two new human caspase recruitment domain (CARD) molecules, termed Pseudo-interleukin-1beta converting enzyme (ICE) and ICEBERG. Both proteins share a high degree of homology, reaching 92% and 53% identity, respectively, to the prodomain of caspase-1/ICE. Interestingly, both Pseudo-ICE and ICEBERG are mapped to chromosome 11q22 that bears caspases-1, -4- and -5 genes, all involved in cytokine production rather than in apoptosis. We demonstrate that Pseudo-ICE and ICEBERG interact physically with caspase-1 and block, in a monocytic cell line, the interferon-gamma and lipopolysaccharide-induced secretion of interleukin-1beta which is a well-known consequence of caspase-1 activation. Moreover, Pseudo-ICE, but not ICEBERG, interacts with the CARD-containing kinase RICK/RIP2/CARDIAK and activates NF-kappaB. Our data suggest that Pseudo-ICE and ICEBERG are intracellular regulators of caspase-1 activation and could play a role in the regulation of IL-1beta secretion and NF-kappaB activation during the pro-inflammatory cytokine response.

There exists considerable research on the effects of prenatal maternal stress on offspring. Animal studies, using random assignment to experimental and control groups, demonstrate the noxious effects of prenatal maternal stress on physical, behavioural and cognitive development. The generalizability of these results to humans is problematic given that cognitive attributions moderate reactions to stressors. In humans, researchers have relied upon maternal anxiety or exposure to life events as proxies for the stressors used with animals. Yet, the associations between maternal anxiety or potentially non-independent life events and problems in infants are confounded by genetic transmission of temperament from mother to child. We summarize the literature on prenatal maternal stress and infant cognitive development, leading to the conclusion that the human literature lacks the ability to separate the effects of the objective exposure to a stressor and the mother's subjective reaction. We then describe our prospective Project Ice Storm in which we are following 150 children who were exposed in utero to a natural disaster. We demonstrate significant effects of the objective severity of exposure on cognitive and language development at age two years with important moderating effects of the timing during pregnancy. The implications of our findings are discussed.

The Southern Ocean around Antarctica is among the most rapidly warming regions on Earth, but has experienced episodic climate change during the past 40 million years. It remains unclear how ancient periods of climate change have shaped Antarctic biodiversity. The origin of antifreeze glycoproteins (AFGPs) in Antarctic notothenioid fishes has become a classic example of how the evolution of a key innovation in response to climate change can drive adaptive radiation. By using a time-calibrated molecular phylogeny of notothenioids and reconstructed paleoclimate, we demonstrate that the origin of AFGP occurred between 42 and 22 Ma, which includes a period of global cooling approximately 35 Ma. However, the most species-rich lineages diversified and evolved significant ecological differences at least 10 million years after the origin of AFGPs, during a second cooling event in the Late Miocene (11.6-5.3 Ma). This pattern indicates that AFGP was not the sole trigger of the notothenioid adaptive radiation. Instead, the bulk of the species richness and ecological diversity originated during the Late Miocene and into the Early Pliocene, a time coincident with the origin of polar conditions and increased ice activity in the Southern Ocean. Our results challenge the current understanding of the evolution of Antarctic notothenioids suggesting that the ecological opportunity that underlies this adaptive radiation is not linked to a single trait, but rather to a combination of freeze avoidance offered by AFGPs and subsequent exploitation of new habitats and open niches created by increased glacial and ice sheet activity.

The present paper reviews the effects of water temperature and flow on migrations, embryonic development, hatching, emergence, growth and life-history traits in light of the ongoing climate change with emphasis on anadromous Atlantic salmon Salmo salar and brown trout Salmo trutta. The expected climate change in the Atlantic is for milder and wetter winters, with more precipitation falling as rain and less as snow, decrease in ice-covered periods and frequent periods with extreme weather. Overall, thermal limits for salmonids are species specific. Scope for activity and growth and optimal temperature for growth increase with temperature to an optimal point before constrain by the oxygen content of the water. The optimal temperature for growth decreases with increasing fish size and varies little among populations within species, whereas the growth efficiency may be locally adapted to the temperature conditions of the home stream during the growth season. Indirectly, temperature influences age and size at smolting through its effect on growth. Time of spawning, egg hatching and emergence of the larvae vary with temperature and selective effects on time of first feeding. Traits such as age at first maturity, longevity and fecundity decrease with increasing temperature whilst egg size increases with temperature. Water flow influences the accessibility of rivers for returning adults and speed of both upstream and downstream migration. Extremes in water flow and temperature can decrease recruitment and survival. There is reason to expect a northward movement of the thermal niche of anadromous salmonids with decreased production and population extinction in the southern part of the distribution areas, migrations earlier in the season, later spawning, younger age at smolting and sexual maturity and increased disease susceptibility and mortality. Future research challenges are summarized at the end of the paper.