Climate change, coral bleaching and the future of the world's coral reefs

Sea temperatures in many tropical regions have increased by almost 1 degrees C over the past 100 years, and are currently increasing at similar to 1-2 degrees C per century. Coral bleaching occurs when the thermal tolerance of corals and their photosynthetic symbionts (zooxanthellae) is exceeded. Mass coral bleaching has occurred in association with episodes of elevated sea temperatures over the past 20 years and involves the loss of the zooxanthellae following chronic photoinhibition. Mass bleaching has resulted in significant losses of live coral in many parts of the world. This paper considers the biochemical, physiological and ecological perspectives of coral bleaching. It also uses the outputs of four runs from three models of global climate change which simulate changes in sea temperature and hence how the frequency and intensity of bleaching events will change over the next 100 years. The results suggest that the thermal tolerances of reef-building corals are likely to be exceeded every year within the next few decades. Events as severe as the 1998 event, the worst on record, are likely to become commonplace within 20 years. Most information suggests that the capacity for acclimation by corals has already been exceeded, and that adaptation will be too slow to avert a decline in the quality of the world's reefs. The rapidity of the changes that are predicted indicates a major problem for tropical marine ecosystems and suggests that unrestrained warming cannot occur without the loss and degradation of coral reefs on a global scale.

Structural basis of recognition of monopartite and bipartite nuclear localization sequences by mammalian importin-alpha

Importin-alpha is the nuclear import receptor that recognizes cargo proteins which contain classical monopartite and bipartite nuclear localization sequences (NLSs), and facilitates their transport into the nucleus. To determine the structural basis of the recognition of the two classes of NLSs by mammalian importin-alpha, we co-crystallized an N-terminally truncated mouse receptor protein with peptides corresponding to the monopartite NLS from the simian virus 40 (SV40) large T-antigen, and the bipartite NLS from nucleoplasmin. We show that the monopartite SV40 large T-antigen NLS binds to two binding sites on the receptor, similar to what was observed in yeast importin-alpha. The nucleoplasmin NLS-importin-alpha complex shows, for the first time, the mode of binding of bipartite NLSs to the receptor. The two basic clusters in the NLS occupy the two binding sites used by the monopartite NLS, while the sequence linking the two basic clusters is poorly ordered, consistent with its tolerance to mutations. The structures explain the structural basis for binding of diverse NLSs to the sole receptor protein. (C) 2000 Academic Press.

MDMA (Ecstasy) neurotoxicity: assessing and communicating the risks

MDMA (3,4-methylenedioxymethamphetamine) is an amphetamine analogue that produces euphoric and stimulant effects and a feeling of closeness towards others.1 and 2 For more than a decade, MDMA (colloquially known as “Ecstasy” or “E”) has been widely used by young adults as a dance-party drug. The usual recreational oral dose is 1-2 tablets (each containing about 60-120 mg of MDMA) a standard oral dose of 0·75–4·00 mg per kg in 60–80 kg people. MDMA is typically used once fortnightly or less because tolerance to the effects of MDMA develops rapidly. More frequent use requires larger doses to achieve the desired effects, but this increases the prevalence of unpleasant side-effects.3 A number of deaths have occurred as a result of malignant hyperthermia or idiosyncractic reactions to the drug, but these have been rare.4 MDMA is perceived by many users to be a safe drug.1 Few report the craving associated with opiates or cocaine3 and most MDMA users are aware of only mild and transient disruptions of functioning.3 and 5 AC Parrott and J Lasky, Ecstasy (MDMA) effects upon mood and cognition: before, during and after a Saturday night dance, Psychopharmacology 139 (1998), pp. 261–268. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (174)5 The perceived safety of MDMA is at odds with animal evidence of MDMA neurotoxicity, an increasing prevalence of hazardous patterns of use among recreational MDMA users, and emerging evidence of neurotoxicity among heavier MDMA users.

Comparative analysis of dendritic cell density and total number in commonly transplanted organs: morphometric estimation in normal mice

Dendritic cells (DC) are considered to be the major cell type responsible for induction of primary immune responses. While they have been shown to play a critical role in eliciting allosensitization via the direct pathway, there is evidence that maturational and/or activational heterogeneity between DC in different donor organs may be crucial to allograft outcome. Despite such an important perceived role for DC, no accurate estimates of their number in commonly transplanted organs have been reported. Therefore, leukocytes and DC were visualized and enumerated in cryostat sections of normal mouse (C57BL/10, B10.BR, C3H) liver, heart, kidney and pancreas by immunohistochemistry (CD45 and MHC class II staining, respectively). Total immunopositive cell number and MHC class II+ cell density (C57BL/10 mice only) were estimated using established morphometric techniques - the fractionator and disector principles, respectively. Liver contained considerably more leukocytes (similar to 5-20 x 10(6)) and DC (similar to 1-3 x 10(6)) than the other organs examined (pancreas: similar to 0.6 x 10(6) and similar to 0.35 x 10(6): heart: similar to 0.8 x 10(6) and similar to 0.4 x 10(6); kidney similar to 1.2 x 10(6) and 0.65 x 10(6), respectively). In liver, DC comprised a lower proportion of all leukocytes (similar to 15-25%) than in the other parenchymal organs examined (similar to 40-60%). Comparatively, DC density in C57BL/10 mice was heart > kidney > pancreas much greater than liver (similar to 6.6 x 10(6), 5 x 10(6), 4.5 x 10(6) and 1.1 x 10(6) cells/cm(3), respectively). When compared to previously published data on allograft survival, the results indicate that the absolute number of MHC class II+ DC present in a donor organ is a poor predictor of graft outcome. Survival of solid organ allografts is more closely related to the density of the donor DC network within the graft. (C) 2000 Elsevier Science B.V. All rights reserved.

Inability of adult Limnodynastes peronii (Amphibia : Anura) to thermally acclimate locomotor performance

Despite several studies on adult amphibians, only larvae of the striped marsh frog (Limnodynastes peronii) have been reported to possess the ability to compensate for the effects of cool temperature on locomotor performance by thermal acclimation. In this study, we investigated whether this thermal acclimatory ability is shared by adult L. peronii. We exposed adult L. peronii to either 18 or 30 degrees C for 8 weeks and tested their swimming and jumping performance at six temperatures between 8 and 35 degrees C. Acute changes in temperature affected both maximum swimming and jumping performance, however there was no difference between the two treatment groups in locomotor performance between 8 and 30 degrees C. Maximum swimming velocity of both groups increased from 0.62 +/- 0.02 at 8 degrees C to 1.02 +/- 0.03 m s(-1) at 30 degrees C, while maximum jump distance increased from similar to 20 to > 60 cm over the same temperature range. Although adult L. peronii acclimated to 18 degrees C failed to produce a locomotor response at 35 degrees C, this most likely reflected a change in thermal tolerance limits with acclimation rather than modifications in the locomotor system. As all adult amphibians studied to date are incapable of thermally acclimating locomotor performance, including adults of L. peronii, this acclimatory capacity appears to be absent from the adult stage of development. (C) 2000 Elsevier Science Inc. All rights reserved.

Nitrogen dynamics and the physiological basis of stay-green in sorghum

Sorghum [Sorghum bicolor (L,) Moench] hybrids containing the stay-green trait retain more photosynthetically active leaves under drought than do hybrids that do not contain this trait. Since the Longevity and photosynthetic capacity of a leaf are related to its N status, it is important to clarify the role of N in extending leaf greenness in stay-green hybrids. Field studies were conducted in northeastern Australia to examine the effect of three water regimes and nine hybrids on N uptake and partitioning among organs. Nine hybrids varying in the B35 and KS19 sources of stay-green were grown under a fully irrigated control, post-flowering water deficit, and terminal water deficit. For hybrids grown under terminal water deficit, stay-green was viewed as a consequence of the balance between N demand by the grain and N supply during gain filling. On the demand side, grain numbers were 16% higher in the four stay-green than in the five senescent hybrids. On the supply side, age-related senescence provided an average of 34 and 42 kg N ha(-1) for stay-green and senescent hybrids, respectively. In addition, N uptake during grain filling averaged 116 and 82 kg ha(-1) in stay-green and senescent hybrids. Matching the N supply from these two sources with grain N demand found that the shortfall in N supply for grain filling in the stay-green and senescent hybrids averaged 32 and 41 kg N ha(-1) resulting in more accelerated leaf senescence in the senescent hybrids. Genotypic differences in delayed onset and reduced rate of leaf senescence were explained by differences in specific leaf nitrogen and N uptake during grain filling. Leaf nitrogen concentration at anthesis was correlated with onset (r = 0.751**, n = 27) and rate (r = -0.783**, n = 27) of leaf senescence ender terminal water deficit.

Ischaemic preconditioning in the rat brain: a longitudinal magnetic resonance imaging (MRI) study

Ischaemic preconditioning in rats was studied using MRI. Ischaemic preconditioning was induced, using an intraluminal filament method, by 30 min middle cerebral artery occlusion (MCAO), and imaged 24 h later. The secondary insult of 100 min MCAO was induced 3 days following preconditioning and imaged 24 and 72 h later. Twenty four hours following ischaemic preconditioning most rats showed small sub-cortical hyperintense regions not seen in sham-preconditioned rats. Twenty-four hours and 72 h following the secondary insult preconditioned animals showed significantly smaller lesions (24 h = 112 +/- 31 mm(3), mean +/- standard error; 72 h = 80 +/- 35 mm(3)) which were confined to the striatum, than controls (24 h = 234 +/- 32 mm(3), p = 0.026; 72 h = 275 +/- 37 mm(3), p = 0.003). In addition during Lesion maturation from 24 to 72 h post-secondary MCAO, preconditioned rats displayed an average reduction in lesion size as measured by MRI whereas sham-preconditioned rats displayed increases in lesion size; this is the first report of such differential lesion volume evolution in cerebral ischaemic preconditioning. Copyright (C) 2001 John Wiley & Sons, Ltd.

Heroin overdose: causes and consequences

Over the past decade fatal opioid overdose has emerged as a major public health issue internationally. This paper examines the risk factors for overdose from a biomedical perspective. while significant risk factors for opioid overdose fatality are well recognized, the mechanism of fatal overdose remains unclear. Losses of tolerance and concomitant use of alcohol and other CNS depressants clearly play a major role in fatality; howeve, such risk factors do not account for the strong age and gender patterns observed consistently among victims of overdose. There is evidence that systemic disease may be more prevalent in users at greatest risk of overdose. We hypothesize that pulmonary and hepatic dysfunction resulting from such disease may increase susceptibility to both fatal and non-fatal overdose. Sequelae of non-fatal overdose are recognized in the clinical literature but few epidemiological data exist describing the burden of morbidity arising from such sequelae. The potential for overdose to cause persisting morbidity is reviewed.

Immunobiology of liver dendritic cells

Dendritic cells (DC) are rare, bone marrow-derived antigen-presenting cells that play a critical role in the induction and regulation of immune reactivity. In this article, we review the identification and characterization of liver DC, their ontogenic development, in vivo mobilization and population dynamics. In addition, we discuss the functions of DC isolated from liver tissue or celiac lymph, or propagated in vitro from liver-resident haemopoietic stem/progenitor cells. Evidence concerning the role of DC in viral hepatitis. liver tumours, autoimmune liver diseases, granulomatous inflammation and the outcome of liver transplantation is also discussed.

Resistance to UVB radiation in Antarctic yeasts

Yeast cells were used as a model system to study the inter-relationship among free radicals, antioxidants and UV-induced cell damage. In particular, the effects of UV-radiation in newly isolated yeasts from the Antarctic have been studied.

Association of increased levels of heavy-chain ferritin with increased CD4(+) CD25(+) regulatory T-Cell levels in patients with melanoma

We have shown previously that melanoma cells in culture release heavy-chain ferritin (H-Ferritin) into supernatants and that this is responsible for the suppression of responses of peripheral blood lymphocytes stimulated by anti-CD3. These effects were mediated by activation of regulatory T cells to produce interleukin (IL)-10. In the present study, we examined whether a similar relation might exist between levels of H-Ferritin and activation of regulatory T cells in patients with melanoma. Ferritin levels were evaluated by ELISA and regulatory T-cell numbers were assessed by three-color flow cytometry to identify CD4(+) CD25(+) CD69(-) T cells. CD69 positive cells were excluded to avoid inclusion of normal activated CD4, CD25 expressing T cells. Measurements of H- and light-chain (L)-Ferritin by ELISA revealed that H- but not L-Ferritin was elevated in the circulation of melanoma patients. In addition, these studies revealed a marked increase in the number of CD4+ CD25+ CD69- T cells in such patients, compared with age-matched controls. The ratio of H-Ferritin:L-Ferritin correlated with the levels of regulatory T cells consistent with a causal relation between unbound H-Ferritin levels and the activation of regulatory T cells. H-Ferritin or regulatory T cells did not, however, correlate with the stage of the melanoma. These results provide evidence for the importance of H-Ferritin in the induction of regulatory T cells in patients with melanoma and provide additional insight into the suppression of immune responses in such patients.

Most lymphoid organ dendritic cell types are phenotypically and functionally immature

Dendritic cells (DCs) have been thought to follow a life history, typified by Langerhans cells (LCs), with 2 major developmental stages: an immature stage that captures antigens in the periphery and a mature stage that presents those antigens in the lymphoid organs. However, a systematic assessment of the maturity of lymphoid organ DCs has been lacking. We have analyzed the maturity of the DC types found in the steady state in the spleen, lymph nodes (LNs), and thymus. The DCs that migrate into the iliac, mesenteric, mediastinal, or subcutaneous LNs from peripheral tissues were mature and therefore could not process and present newly encountered antigens. However, all the other DC types were phenotypically and functionally immature: they expressed low levels of surface major histocompatibility complex class 11 (MHC 11) and CD86, accumulated MHC 11 in their endosomes, and could present newly encountered antigens. These immature DCs could 1346 induced to mature by culture in vitro or by Inoculation of inflammatory stimuli in vivo. Therefore, the lymphoid organs contain a large cohort of immature DCs, most likely for the maintenance of peripheral tolerance, which can respond to infections reaching those organs and mature in situ. (C) 2003 by The American Society of Hematology.

Seedling responses of four Australian tree species to toxic concentrations of manganese in solution culture

Little is known about the responses of Australian plants to excess metal, including Mn. It is important to remedy this lack of information so that knowledgeable decisions can be made about managing Mn contaminated sites where inhabited by Australian vegetation. Acacia holosericea, Melaleuca leucadendra, Eucalyptus crebra and Eucalyptus camaldulensis were grown in dilute solution culture for 10 weeks. The seedlings ( 42 days old) were exposed to six Mn treatments viz., 1, 8, 32, 128, 512 and 2048 muM. The order of tolerance to toxic concentrations of Mn was A. holosericea congruent to = E. crebra < M. leucadendra < E. camaldulensis, the critical external concentrations being approximately 5.1, 5.0, 21 and 330 muM, respectively. The critical tissue Mn concentrations for the youngest fully expanded leaf and total shoots were, respectively, 265 and 215 mug g(-1) DM for A. holosericea, 445 and 495 mug g(-1) DM for M. leucadendra, 495 and 710 mug g(-1) DM for E. crebra and 7230 and 6510 mug g(-1) DM for E. camaldulensis. The high tolerance of E. camaldulensis ( as opposed to the sensitivity of E. crebra) to excess Mn raises concern about fauna feeding on the plant and is consistent with hypotheses suggesting the Eucalyptus subgenus Symphomyrtus is particularly tolerant of stress, including excess Mn. The results from this paper provide the first comprehensive combination of growth responses, critical external concentrations, critical tissue concentrations and plant toxicity symptoms for three important Australian genera, viz., Eucalyptus, Acacia and Melaleuca, for use in the management of Mn toxic sites.

Antigen-specific suppression of inflammatory arthritis by dendritic cells

Purpose Antigen-specific suppression of a previously primed immune response is a major challenge for immunotherapy of autoimmune disease. We have shown that NF-κB inactivation in dendritic cells (modified DC) converts them into cells that tolerize rather than immunize to specific antigen [1]. Antigen-exposed modified DC prevent priming of immunity, and they suppress previously primed immune responses. Regulatory CD4+ T cells, which can transfer antigen-specific tolerance in an IL-10-dependent fashion, mediate the tolerance. We hypothesized that modified DC exposed to arthritogenic antigen would suppress clinical arthritis after disease onset. Methods Antigen-induced arthritis was induced in C57/Bl6 mice by priming to methylated bovine serum albumin (mBSA) antigen followed by challenge injection of mBSA to one knee. Knee swelling was apparent within 2 days, with peak clinical signs apparent at 5 days. Mice were treated with antigen-exposed modified DC between 2 and 6 days after mBSA challenge to the knee joint. Results Clinical arthritis was suppressed in each group receiving mBSA-exposed modified DC within 4 days compared with mice that received either no DC or keyhole limpet hemocyanin-exposed modified DC. Clinical improvement was associated with mBSA-specific tolerance in mice receiving mBSA-exposed modified DC. Tolerance induction was not impaired by concomitant administration of anti-tumor necrosis factor alpha monoclonal antibody. Subsequent rechallenge with intra-articular IL-1 induced flare of arthritis in all groups, which could be effectively suppressed by a second administration of mBSA-exposed modified DC. Conclusions The data indicate that modified DC induce antigen-specific immune suppression in this model of inflammatory arthritis, even after full clinical expression of the disease. These observations have important implications for antigen-specific therapy of autoimmunity.

Naloxone fails to antagonize initial hypoalgesic effect of a manual therapy treatment for lateral epicondylalgia

Background: Recent research has shown that Mulligan's Mobilization With Movement treatment technique for the elbow (MWM), a peripheral joint mobilization technique, produces a substantial and immediate pain relief in chronic lateral epicondylalgia (48% increase in pain-free grip strength).(1) This hypoalgesic effect is far greater than that previously reported with spinal manual therapy treatments, prompting speculation that peripheral manual therapy treatments may differ in mechanism of action to spinal manual therapy techniques. Naloxone antagonism and tolerance studies, which employ widely accepted tests for the identification of endogenous opioid-mediated pain control mechanisms, have shown that spinal manual therapy-induced hypoalgesia does not involve an opioid mechanism. Objective: The aim of this study was to evaluate the effect of naloxone administration on the hypoalgesic effect of MWM. Methods: A randomized, controlled trial evaluated the effect of administering naloxone, saline, or no-substance control injection on the MWM-induced hypoalgesia in 18 participants with lateral epicondylalgia. Pain-free grip strength, pressure pain threshold, thermal pain threshold, and upper limb neural tissue provocation test 2b were the outcome measures. Results: The results demonstrated that the initial hypoalgesic effect of the MWM was not antagonized by naloxone, suggesting a nonopioid mechanism of action. Conclusions: The studied peripheral mobilization treatment technique appears to have a similar effect profile to previously studied spinal manual therapy techniques, suggesting a nonopioid-mediated hypoalgesia following manual therapy.