The chironomid-temperature relationship: expression in nature and palaeoenvironmental implications

Fossils of chironomid larvae (non-biting midges) preserved in lake sediments are well-established palaeotemperature indicators which, with the aid of numerical chironomid-based inference models (transfer functions), can provide quantitative estimates of past temperature change. This approach to temperature reconstruction relies on the strong relationship between air and lake surface water temperature and the distribution of individual chironomid taxa (species, species groups, genera) that has been observed in different climate regions (arctic, subarctic, temperate and tropical) in both the Northern and Southern hemisphere. A major complicating factor for the use of chironomids for palaeoclimate reconstruction which increases the uncertainty associated with chironomid-based temperature estimates is that the exact nature of the mechanism responsible for the strong relationship between temperature and chironomid assemblages in lakes remains uncertain. While a number of authors have provided state of the art overviews of fossil chironomid palaeoecology and the use of chironomids for temperature reconstruction, few have focused on examining the ecological basis for this approach. Here, we review the nature of the relationship between chironomids and temperature based on the available ecological evidence. After discussing many of the surveys describing the distribution of chironomid taxa in lake surface sediments in relation to temperature, we also examine evidence from laboratory and field studies exploring the effects of temperature on chironomid physiology, life cycles and behaviour. We show that, even though a direct influence of water temperature on chironomid development, growth and survival is well described, chironomid palaeoclimatology is presently faced with the paradoxical situation that the relationship between chironomid distribution and temperature seems strongest in relatively deep, thermally stratified lakes in temperate and subarctic regions in which the benthic chironomid fauna lives largely decoupled from the direct influence of air and surface water temperature. This finding suggests that indirect effects of temperature on physical and chemical characteristics of lakes play an important role in determining the distribution of lake-living chironomid larvae. However, we also demonstrate that no single indirect mechanism has been identified that can explain the strong relationship between chironomid distribution and temperature in all regions and datasets presently available. This observation contrasts with the previously published hypothesis that climatic effects on lake nutrient status and productivity may be largely responsible for the apparent correlation between chironomid assemblage distribution and temperature. We conclude our review by summarizing the implications of our findings for chironomid-based palaeoclimatology and by pointing towards further avenues of research necessary to improve our mechanistic understanding of the chironomid-temperature relationship.

Intra-annual radial growth and water relations of trees - implications towards a growth mechanism

There is a missing link between tree physiological and wood-anatomical knowledge which makes it impossible mechanistically to explain and predict the radial growth of individual trees from climate data. Empirical data of microclimatic factors, intra-annual growth rates, and tree-specific ratios between actual and potential transpiration (T PET−1) of trees of three species (Quercus pubescens, Pinus sylvestris, and Picea abies) at two dry sites in the central Wallis, Switzerland, were recorded from 2002 to 2004 at a 10 min resolution. This included the exceptionally hot and dry summer of 2003. These data were analysed in terms of direct (current conditions) and indirect impacts (predispositions of the past year) on growth. Rain was found to be the only factor which, to a large extent, consistently explained the radial increment for all three tree species at both sites and in the short term as well. Other factors had some explanatory power on the seasonal time-scale only. Quercus pubescens built up much of its tree ring before bud break. Pinus sylvestris and Picea abies started radial growth 1–2 weeks after Quercus pubescens and this was despite the fact that they had a high T PET−1 before budburst and radial growth started. A high T PET−1 was assumed to be related to open stomata, a very high net CO2 assimilation rate, and thus a potential carbon (C)-income for the tree. The main period of radial growth covered about 30–70% of the productive days of a year. In terms of C-allocation, these results mean that Quercus pubescens depended entirely on internal C-stores in the early phase of radial growth and that for all three species there was a long time period of C-assimilation which was not used for radial growth in above-ground wood. The results further suggest a strong dependence of radial growth on the current tree water relations and only secondarily on the C-balance. A concept is discussed which links radial growth over a feedback loop to actual tree water-relations and long-term affected C-storage to microclimate.

Prolactin upregulates sphingosine kinase-1 expression and activity in the human breast cancer cell line MCF7 and triggers enhanced proliferation and migration

Sphingosine kinases (SK) catalyze the formation of sphingosine-1-phosphate (S1P) which plays a crucial role in cell growth and survival. Here, we show that prolactin (PRL) biphasically activates the SK-1, but not the SK-2 subtype, in the breast adenocarcinoma cell-line MCF7. A first peak occurs after minutes of stimulation and is followed by a second delayed activation after hours of stimulation. A similar biphasic effect on SK-1 activity is seen for 17beta-estradiol (E(2)). The delayed activation of SK-1 derives from an upregulated mRNA and protein expression and is due to increased SK-1 promoter activity and mechanistically involves STAT5 activation as well as protein kinase C and the classical mitogen-activated protein kinases. Furthermore, glucocorticoids also block both hormone-induced SK-1 expression and activity. Functionally, long-term stimulation of MCF7 cells with PRL or E(2) is well known to trigger increased cell proliferation and migration. Both hormone-induced cell responses critically involve SK-1 activation since the depletion of SK-1, but not SK-2, by siRNA transfection abolishes the hormone-induced cell proliferation and migration. In summary, our data show that PRL and E(2) cause a pronounced delayed SK-1 activation which is due to increased gene transcription, and critically determines the capability of cells to grow and move. Thus, the SK-1 may represent a novel attractive target for anti-tumor therapy.

The influence of local and systemic preconditioning on oxygenation, metabolism and survival in critically ischaemic skin flaps in pigs

Stress proteins represent a group of highly conserved intracellular proteins that provide adaptation against cellular stress. The present study aims to elucidate the stress protein-mediated effects of local hyperthermia and systemic administration of monophosphoryl lipid A (MPL) on oxygenation, metabolism and survival in bilateral porcine random pattern buttock flaps. Preconditioning was achieved 24h prior to surgery by applying a heating blanket on the operative site (n = 5), by intravenous administration of MPL at a dosage of 35 microg/kg body weight (n = 5) or by combining the two (n = 5). The flaps were monitored with laser Doppler flowmetry, polarographic microprobes and microdialysis until 5h postoperatively. Semiquantitative immunohistochemistry was performed for heat shock protein 70 (HSP70), heat shock protein 32 (also termed haem oxygenase-1, HO-1), and inducible nitrc oxide synthase (iNOS). The administration of MPL increased the impaired microcirculatory blood flow in the proximal part of the flap and partial oxygen tension in the the distal part by approximately 100% each (both P<0.05), whereas both variables remained virtually unaffected by local heat preconditioning. Lactate/pyruvate (L/P) ratio and glycerol concentration (representing cell membrane disintegration) in the distal part of the flap gradually increased to values of approximately 500 mmol/l and approximately 350 micromol/l, respectively (both P<0.01), which was substantially attenuated by heat application (P<0.01 for L/P ratio and P<0.05 for glycerol) and combined preconditioning (P<0.01 for both variables), whereas the effect of MPL was less marked (not significant). Flap survival was increased from 56% (untreated animals) to 65% after MPL (not significant), 71% after heat application (P<0.05) and 78% after both methods of preconditioning (P<0.01). iNOS and HO-1 were upregulated after each method of preconditioning (P<0.05), whereas augmented HSP70 staining was only observed after heat application (P<0.05). We conclude that local hyperthermia is more effective in preventing flap necrosis than systemic MPL administration because of enhancing the cellular tolerance to hypoxic stress, which is possibly mediated by HSP70, whereas some benefit may be obtained with MPL due to iNOS and HO-1-mediated improvement in tissue oxygenation.

GH mutant (R77C) in a pedigree presenting with the delay of growth and pubertal development: structural analysis of the mutant and evaluation of the biological activity

A heterozygous missense mutation in the GH-1 gene converting codon 77 from arginine (R) to cysteine (C), which was previously reported to have some GH antagonistic effect, was identified in a Syrian family. The index patient, a boy, was referred for assessment of his short stature (-2.5 SDS) at the age of 6 years. His mother and grandfather were also carrying the same mutation, but did not differ in adult height from the other unaffected family members. Hormonal examination in all affected subjects revealed increased basal GH, low IGF-I concentrations, and subnormal IGF-I response in generation test leading to the diagnosis of partial GH insensitivity. However, GH receptor gene (GHR) sequencing demonstrated no abnormalities. As other family members carrying the GH-R77C form showed similar alterations at the hormonal level, but presented with normal final height, no GH therapy was given to the boy, but he was followed through his pubertal development which was delayed. At the age of 20 years he reached his final height, which was normal within his parental target height. Functional characterization of the GH-R77C, assessed through activation of Jak2/Stat5 pathway, revealed no differences in the bioactivity between wild-type-GH (wt-GH) and GH-R77C. Detailed structural analysis indicated that the structure of GH-R77C, in terms of disulfide bond formation, is almost identical to that of the wt-GH despite the introduced mutation (Cys77). Previous studies from our group demonstrated a reduced capability of GH-R77C to induce GHR/GH-binding protein (GHBP) gene transcription rate when compared with wt-GH. Therefore, reduced GHR/GHBP expression might well be the possible cause for the partial GH insensitivity found in our patients. In addition, this group of patients deserve further attention because they could represent a distinct clinical entity underlining that an altered GH peptide may also have a direct impact on GHR/GHBP gene expression causing partial GH insensitivity. This might be responsible for the delay of growth and pubertal development. Finally, we clearly demonstrate that GH-R77C is not invariably associated with short stature, but that great care needs to be taken in ascribing growth failure to various heterozygous mutations affecting the GH-IGF axis and that careful functional studies are mandatory.

A systematic review of the success of sinus floor elevation and survival of implants inserted in combination with sinus floor elevation. Part II: transalveolar technique

OBJECTIVES: The objectives of this systematic review were to assess the survival rate of implants placed in sites with transalveolar sinus floor elevation. MATERIAL AND METHODS: An electronic search was conducted to identify prospective and retrospective cohort studies on transalveolar sinus floor elevation, with a mean follow-up time of at least 1 year after functional loading. Failure and complication rates were analyzed using random-effects Poisson regression models to obtain summary estimates/ year proportions. RESULTS: The search provided 849 titles. Full-text analysis was performed for 176 articles, resulting in 19 studies that met the inclusion criteria. Meta-analysis of these studies indicated an estimated annual failure rate of 2.48% (95% confidence interval (95% CI): 1.37-4.49%) translating to an estimated survival rate of 92.8% (95% CI): 87.4-96.0%) for implants placed in transalveolarly augmented sinuses, after 3 years in function. Furthermore, subject-based analysis revealed an estimated annual failure of 3.71% (95% CI: 1.21-11.38%), translating to 10.5% (95% CI: 3.6-28.9%) of the subjects experiencing implant loss over 3 years. CONCLUSION: Survival rates of implants placed in transalveolar sinus floor augmentation sites are comparable to those in non-augmented sites. This technique is predictable with a low incidence of complications during and post-operatively.

A systematic review of the success of sinus floor elevation and survival of implants inserted in combination with sinus floor elevation

OBJECTIVES: The objectives of this systematic review were to assess the survival rate of grafts and implants placed with sinus floor elevation. MATERIAL AND METHODS: An electronic search was conducted to identify studies on sinus floor elevation, with a mean follow-up time of at least 1 year after functional loading. RESULTS: The search provided 839 titles. Full-text analysis was performed for 175 articles resulting in 48 studies that met the inclusion criteria, reporting on 12,020 implants. Meta-analysis indicated an estimated annual failure rate of 3.48% [95% confidence interval (CI): 2.48%-4.88%] translating into a 3-year implant survival of 90.1% (95% CI: 86.4%-92.8%). However, when failure rates was analyzed on the subject level, the estimated annual failure was 6.04% (95% CI: 3.87%-9.43%) translating into 16.6% (95% CI: 10.9%-24.6%) of the subjects experiencing implant loss over 3 years. CONCLUSION: The insertion of dental implants in combination with maxillary sinus floor elevation is a predictable treatment method showing high implant survival rates and low incidences of surgical complications. The best results (98.3% implant survival after 3 years) were obtained using rough surface implants with membrane coverage of the lateral window.

Thiazolides inhibit growth and induce glutathione-S-transferase Pi (GSTP1)-dependent cell death in human colon cancer cells

Thiazolides are a novel class of broad-spectrum anti-infective drugs with promising in vitro and in vivo activities against intracellular and extracellular protozoan parasites. The nitrothiazole-analogue nitazoxanide (NTZ; 2-acetolyloxy-N-(5-nitro 2-thiazolyl) benzamide) represents the thiazolide parent compound, and a number of bromo- and carboxy-derivatives with differing activities have been synthesized. Here we report that NTZ and the bromo-thiazolide RM4819, but not the carboxy-thiazolide RM4825, inhibited proliferation of the colon cancer cell line Caco2 and nontransformed human foreskin fibroblasts (HFF) at or below concentrations the compounds normally exhibit anti-parasitic activity. Thiazolides induced typical signs of apoptosis, such as nuclear condensation, DNA fragmentation and phosphatidylserine exposure. Interestingly, the apoptosis-inducing effect of thiazolides appeared to be cell cycle-dependent and induction of cell cycle arrest substantially inhibited the cell death-inducing activity of these compounds. Using affinity chromatography and mass spectrometry glutathione-S-transferase P1 (GSTP1) from the GST class Pi was identified as a major thiazolide-binding protein. GSTP1 expression was more than 10 times higher in the thiazolide-sensitive Caco2 cells than in the less sensitive HFF cells. The enzymatic activity of recombinant GSTP1 was strongly inhibited by thiazolides. Silencing of GSTP1 using siRNA rendered cells insensitive to RM4819, while overexpression of GSTP1 increased sensitivity to RM4819-induced cell death. Thiazolides may thus represent an interesting novel class of future cancer therapeutics.