Do synovial biopsies help to support evidence for involvement of innate immunity in the immunopathology of Beh?et's disease?

Behçet's disease is a complex vasculitis of unknown etiology. Abundant neutrophils suggest the involvement of innate immunity. Cytokines are skewed to the T-helper-1 pattern. Few sterile organs are easily accessible for analysis in Behçet's disease. Cañete and coworkers identify inflamed joints as a feasible model and suggest the involvement of innate immunity in Behçet's disease.     

Checklist of the Caesalpinioideae (Leguminosae) of Equatorial Guinea (Annobón, Bioko and Río Muni)

This study provides a checklist of the Caesalpinioideae (Leguminosae) present in Equatorial Guinea, comprising 52 genera and 124 taxa. Seven species are known from Annobón, 33 from Bioko and 109 from Río Muni. The best represented genus is Senna with eight species. In addition, bibliographic references for Caesalpinioideae (Leguminosae) from Equatorial Guinea have been gathered and checked. Fourteen species are included based on literature records, because their distribution ranges suggest they may occur in Equatorial Guinea, 11 introduced species could be naturalized, and 45 taxa are recorded for the first time from the country. This represents an increase of over 35% in the floristic knowledge of Caesalpinioideae from Equatorial Guinea. A statistical summary is presented at the end of the checklist.  © 2006 The Linnean Society of London, Botanical Journal of the Linnean Society , 2006, 151 , 541–562.     

Genetic Variants in Inflammation-Related Genes Are Associated with Radiation-Induced Toxicity Following Treatment for Non-Small Cell Lung Cancer

Treatment of non-small cell lung cancer (NSCLC) with radiotherapy or chemoradiotherapy is often accompanied by the development of esophagitis and pneumonitis. Identifying patients who might be at increased risk for normal tissue toxicity would help in determination of the optimal radiation dose to avoid these events. We profiled 59 single nucleotide polymorphisms (SNPs) from 37 inflammation-related genes in 173 NSCLC patients with stage IIIA/IIIB (dry) disease who were treated with definitive radiation or chemoradiation. For esophagitis risk, nine SNPs were associated with a 1.5- to 4-fold increase in risk, including three PTGS2 (COX2) variants: rs20417 (HR:1.93, 95% CI:1.10–3.39), rs5275 (HR:1.58, 95% CI:1.09–2.27), and rs689470 (HR:3.38, 95% CI:1.09–10.49). Significantly increased risk of pneumonitis was observed for patients with genetic variation in the proinflammatory genes IL1A, IL8, TNF, TNFRSF1B, and MIF. In contrast, NOS3:rs1799983 displayed a protective effect with a 45% reduction in pneumonitis risk (HR:0.55, 95% CI:0.31–0.96). Pneumonitis risk was also modulated by polymorphisms in anti-inflammatory genes, including genetic variation in IL13. rs20541 and rs180925 each resulted in increased risk (HR:2.95, 95% CI:1.14–7.63 and HR:3.23, 95% CI:1.03–10.18, respectively). The cumulative effect of these SNPs on risk was dose-dependent, as evidenced by a significantly increased risk of either toxicity with an increasing number of risk genotypes (P<0.001). These results suggest that genetic variations among inflammation pathway genes may modulate the development of radiation-induced toxicity and, ultimately, help in identifying patients who are at an increased likelihood for such events.     

Trophic niche overlap between sympatric harbour seals (Phoca vitulina) and grey seals (Halichoerus grypus) at the southern limit of their European range (Eastern English Channel)

Sympatric harbour (Phoca vitulina) and grey seals (Halichoerus grypus) are increasingly considered potential competitors, especially since recent local declines in harbour seal numbers while grey seal numbers remained stable or increased at their European core distributions. A better understanding of the interactions between these species is critical for conservation efforts. This study aimed to identify the trophic niche overlap between harbour and grey seals at the southern limit of their European range, in the Baie de Somme (BDS, Eastern English Channel, France), where numbers of resident harbour seals and visiting grey seals are increasing exponentially. Dietary overlap was identified from scat contents using hierarchical clustering. Isotopic niche overlap was quantified using δ¹³C and δ¹⁵N isotopic values from whiskers of 18 individuals, by estimating isotopic standard ellipses with a novel hierarchical model developed in a Bayesian framework to consider both intraindividual variability and interindividual variability. Foraging areas of these individuals were identified from telemetry data. The three independent approaches provided converging results, revealing a high trophic niche overlap due to consumption of benthic flatfish. Two diet clusters were dominated by either small or large benthic flatfish; these comprised 85.5% [CI95%: 80.3%–90.2%] of harbour seal scats and 46.8% [35.1%–58.4%] of grey seal scats. The narrower isotopic niche of harbour seals was nested within that of grey seals (58.2% [22.7%–100%] overlap). Grey seals with isotopic values similar to harbour seals foraged in coastal waters close to the BDS alike harbour seals did, suggesting the niche overlap may be due to individual grey seal strategies. Our findings therefore provide the basis for potential competition between both species (foraging on benthic flatfish close to the BDS). We suggest that a continued increase in seal numbers and/or a decrease in flatfish supply in this area could cause/amplify competitive interactions and have deleterious effects on harbour seal colonies.     

Sensitivity to low-dose/low-LET ionizing radiation in mammalian cells harboring mutations in succinate dehydrogenase subunit C is governed by mitochondria-derived reactive oxygen species

It has been hypothesized that ionizing radiation-induced disruptions in mitochondrial O? metabolism lead to persistent heritable increases in steady-state levels of intracellular superoxide (O?(?U+2212)) and hydrogen peroxide (H?O?) that contribute to the biological effects of radiation. Hamster fibroblasts (B9 cells) expressing a mutation in the gene coding for the mitochondrial electron transport chain protein succinate dehydrogenase subunit C (SDHC) demonstrate increases in steady-state levels of O??- and H?O?. When B9 cells were exposed to low-dose/low-LET radiation (5-50 cGy), they displayed significantly increased clonogenic cell killing compared with parental cells. Clones derived from B9 cells overexpressing a wild-type human SDHC (T4, T8) demonstrated significantly increased surviving fractions after exposure to 5-50 cGy relative to B9 vector controls. In addition, pretreatment with polyethylene glycol-conjugated CuZn superoxide dismutase and catalase as well as adenoviral-mediated overexpression of MnSOD and/or mitochondria-targeted catalase resulted in significantly increased survival of B9 cells exposed to 10 cGy ionizing radiation relative to vector controls. Adenoviral-mediated overexpression of either MnSOD or mitochondria-targeted catalase alone was equally as effective as when both were combined. These results show that mammalian cells over expressing mutations in SDHC demonstrate low-dose/low-LET radiation sensitization that is mediated by increased levels of O??- and H?O?. These results also support the hypothesis that mitochondrial O??- and H?O? originating from SDH are capable of playing a role in low-dose ionizing radiation-induced biological responses.     

Mitochondrial Calcium Uniporter Activity Is Dispensable for MDA-MB-231 Breast Carcinoma Cell Survival

Calcium uptake through the mitochondrial Ca²⁺ uniporter (MCU) is thought to be essential in regulating cellular signaling events, energy status, and survival. Functional dissection of the uniporter is now possible through the recent identification of the genes encoding for MCU protein complex subunits. Cancer cells exhibit many aspects of mitochondrial dysfunction associated with altered mitochondrial Ca²⁺ levels including resistance to apoptosis, increased reactive oxygen species production and decreased oxidative metabolism. We used a publically available database to determine that breast cancer patient outcomes negatively correlated with increased MCU Ca²⁺ conducting pore subunit expression and decreased MICU1 regulatory subunit expression. We hypothesized breast cancer cells may therefore be sensitive to MCU channel manipulation. We used the widely studied MDA-MB-231 breast cancer cell line to investigate whether disruption or increased activation of mitochondrial Ca²⁺ uptake with specific siRNAs and adenoviral overexpression constructs would sensitize these cells to therapy-related stress. MDA-MB-231 cells were found to contain functional MCU channels that readily respond to cellular stimulation and elicit robust AMPK phosphorylation responses to nutrient withdrawal. Surprisingly, knockdown of MCU or MICU1 did not affect reactive oxygen species production or cause significant effects on clonogenic cell survival of MDA-MB-231 cells exposed to irradiation, chemotherapeutic agents, or nutrient deprivation. Overexpression of wild type or a dominant negative mutant MCU did not affect basal cloning efficiency or ceramide-induced cell killing. In contrast, non-cancerous breast epithelial HMEC cells showed reduced survival after MCU or MICU1 knockdown. These results support the conclusion that MDA-MB-231 breast cancer cells do not rely on MCU or MICU1 activity for survival in contrast to previous findings in cells derived from cervical, colon, and prostate cancers and suggest that not all carcinomas will be sensitive to therapies targeting mitochondrial Ca²⁺ uptake mechanisms.