Can patterns of spatial autocorrelation reveal population processes? An analysis with the fire salamander

Spatial autocorrelation (SAC) is often observed in species distribution data, and can be caused by exogenous, autocorrelated factors determining species distribution, or by endogenous population processes determining clustering such as dispersal. However, it remains debated whether SAC patterns can actually reveal endogenous processes. We reviewed studies measuring dispersal of the salamander Salamandra salamandra, to formulate a priori hypotheses on the scale at which dispersal is expected to determine population distribution. We then tested the hypotheses by analysing SAC in distribution data, and evaluating whether controlling for the effect of environmental variables can reveal endogenous processes. We surveyed 565 streams to obtain species distribution data; we also recorded landscape and microhabitat features known to affect the species. We used multiple approaches to tease apart endogenous and exogenous SAC: the analysis of residuals of logistic regression models considering different environmental variables; the analysis of eigenvectors extracted by several implementations of spatial eigenvector mapping. In capture–mark–recapture studies, 98% of individuals moved 500 m or less. Both species distribution and environmental features were strongly autocorrelated. The residuals of logistic regression relating species to environmental variables were autocorrelated at distances up to 500 m; analyses considering different sets of environmental variables, or assuming non‐linear species habitat relationships, yielded identical results. The results of spatial eigenvector mapping strongly depended on the matrix of distances used. Nevertheless, the eigenvectors of models with best fit were autocorrelated at distances up to 200–500 m. The concordance between multiple approaches suggests that 500 m is the scale at which dispersal connects breeding localities, increasing probability of occurrence. If exogenous variables are correctly identified, the analysis of SAC can provide important insights on endogenous population processes, such as the flow of individuals. SAC analysis can also provide important information for conservation, as the existence of metapopulations or population networks is essential for long term persistence of amphibians.     

Use of intercross outbred mice and single nucleotide polymorphisms to map skin cancer modifier loci

Car-R and Car-S outbred mouse lines, phenotypically selected for resistance and susceptibility to skin carcinogenesis respectively, show significant linkage disequilibrium (LD) at genetic markers mapping on chromosomal regions where skin cancer modifier loci (Skts3, Skts1, and Psl1 on Chrs 5, 7, and 9 respectively) have been mapped in standard crosses. Analysis of these regions for genetic linkage with skin cancer phenotypes in 245 (Car-R × Car-S)F₂ intercross mice, by using single nucleotide polymorphisms (SNPs), revealed significant linkage at a possible allelic form of the Skts1 locus, whose mapping region was shortened to a <5.5-cM interval near the Tyr locus. The Car-derived Skts1 locus was linked with papilloma multiplicity and latency by a recessive inheritance of the susceptibility allele. Putative loci on Chr 5 (Skts3) and 9 (Psl1) showed no significant linkage. These results point to the important role of the Stks1 locus in mouse skin tumorigenesis in independent crosses. The shortened Skts1 mapping region should facilitate the identification of candidate genes. Received: 23 June 2000 / Accepted: 22 November 2000     

Cell adhesion protects c-Raf-1 against ubiquitin-dependent degradation by the proteasome

MAP kinase activation by growth factors depends on cell adhesion to the extracellular matrix. Disrupting the cell adhesion process in NIH 3T3 fibroblasts induced an almost complete inhibition of MAP kinase, which was impaired by proteasome inhibitors. In the absence of cell anchorage, c-Raf-1 expression was dramatically decreased after 24 h. This down-regulation was suppressed by proteasome inhibitors, suggesting that a proteasome-dependent degradation of Raf occurred in the absence of cell adhesion. Proteasome inhibitors did not affect Raf-1 levels in adherent cells, indicating that this degradation only occurred in the absence of cell adhesion. Finally, ectopic coexpression of Raf-1 and ubiquitin in HEK-293 and NIH 3T3 cells generated ubiquitylated forms of Raf-1, both in adherent and suspended cells, suggesting a possible ubiquitin-dependent degradation of the protein.     

Risk and Outcome after Ablation of Isthmus-Dependent Atrial Flutter in Elderly Patients

MethodsA total of 1187 patients with a mean age 65±12 years consecutively referred for AFL ablation were retrospectively analyzed in the study.Results445 (37.5%) patients were aged ≥70 (range 70 to 93) among which 345 were aged 70 to 79 years (29.1%) and 100 were aged ≥80 (8.4%). In multivariable analysis, AFL-related rhythmic cardiomyopathy and presentation with 1/1 AFL were less frequent (respectively adjusted OR = 0.44, 0.27–0.74, p = 0.002 and adjusted OR = 0.29, 0.16–0.52, p<0.0001). AFL ablation-related major complications were more frequent in patients ≥70 although remained lower than 10% (7.4% in ≥70 vs. 4.2% in <70, adjusted OR = 1.74, 1.04–2.89, p = 0.03). After 2.1±2.7 years, AFL recurrence was less frequent in patients ≥70 (adjusted OR = 0.54, 0.37–0.80, p = 0.002) whereas atrial fibrillation (AF) occurrence was as frequent in the 70–79 and ≥80 age subsets. As expected, cardiac mortality was higher in older patients. Patients aged ≥80 also had a low probability of AFL recurrence (5.0%) and AF onset (19.0%).ConclusionsOlder patients represent 37.5% of patients referred for AFL ablation and displayed a <10% risk of ablation-related complications. Importantly, AFL recurrences were less frequent in patients ≥70 while AF occurrence was as frequent as in patients <70. Similar observations were made in patients ≥80 years. AFL ablation appears to be safe and efficient and should not be ruled out in elderly patients.     

Linkage disequilibrium and haplotype mapping of a skin cancer susceptibility locus in outbred mice

Car-R (carcinogenesis-resistant) and Car-S (carcinogenesis-susceptible) outbred mice, obtained by phenotypic selection from an initial intercross of eight inbred strains, show a >100-fold difference in their susceptibility to two-stage skin tumorigenesis. We found that the lines carry a high degree of genetic polymorphism, with an average heterozygosity of 0.39. This polymorphism allowed the use of linkage disequilibrium (LD) and haplotype analysis for the mapping of a skin cancer modifier locus on Chr 7, in a short region of 6 cM, around the Tyr gene. Car-S mice inherited the susceptibility allele at this locus from the A/J, BALB/c, SJL/J, and SWR/J strains. Our results demonstrate the feasibility and usefulness of mapping disease genes by LD in phenotypically selected, genetically heterogeneous animals. Received: 16 March 2000 / Accepted: 9 June 2000     

Assessing Coverage,Equity and Quality Gaps in Maternal and Neonatal Care in Sub-Saharan Africa: An Integrated Approach

BackgroundGaps in coverage, equity and quality of health services hinder the achievement of the Millennium Development Goals 4 and 5 in most countries of sub-Saharan Africa as well as in other high-burden countries, yet few studies attempt to assess all these dimensions as part of the situation analysis. We present the base-line data of a project aimed at simultaneously addressing coverage, equity and quality issues in maternal and neonatal health care in five districts belonging to three African countries.MethodsData were collected in cross-sectional studies with three types of tools. Coverage was assessed in three hospitals and 19 health centres (HCs) utilising emergency obstetric and newborn care needs assessment tools developed by the Averting Maternal Death and Disability program. Emergency obstetrics care (EmOC) indicators were calculated. Equity was assessed in three hospitals and 13 HCs by means of proxy wealth indices and women delivering in health facilities were compared with those in the general population to identify inequities. Quality was assessed in three hospitals using the World Health Organization’s maternal and neonatal quality of hospital care assessment tool which evaluates the whole range of aspects of obstetric and neonatal care and produces an average score for each main area of care.ResultsAll the three hospitals qualified as comprehensive EmOC facilities but none of the HCs qualified for basic EmOC. None of the districts met the minimum requisites for EmOC indicators. In two out of three hospitals, there were major quality gaps which were generally greater in neonatal care, management of emergency and complicated cases and monitoring. Higher access to care was coupled by low quality and good quality by very low access. Stark inequities in utilisation of institutional delivery care were present in all districts and across all health facilities, especially at hospital level.ConclusionOur findings confirm the existence of serious issues regarding coverage, equity and quality of health care for mothers and newborns in all study districts. Gaps in one dimension hinder the potential gains in health outcomes deriving from good performances in other dimensions, thus confirm the need for a three-dimensional profiling of health care provision as a basis for data-driven planning.     

Dimeric Smac mimetics/IAP inhibitors as in vivo-active pro-apoptotic agents. Part II: Structural and biological characterization

Novel pro-apoptotic, homodimeric and heterodimeric Smac mimetics/IAPs inhibitors connected through head–head (8), tail–tail (9) or head–tail linkers (10), were biologically and structurally characterized. In vitro characterization (binding to BIR3 and linker-BIR2–BIR3 domains from XIAP and cIAP1, cytotoxicity assays) identified early leads from each dimer family. Computational models and structural studies (crystallography, NMR, gel filtration) partially rationalized the observed properties for each dimer class. Tail–tail dimer 9a was shown to be active in a breast and in an ovary tumor model, highlighting the potential of dimeric Smac mimetics/IAP inhibitors based on the N-AVPI-like 4-substituted 1-aza-2-oxobicyclo[5.3.0]decane scaffold as potential antineoplastic agents.     

Urothelial cell changes due to busulfan and cyclophosphamide treatment in bone marrow transplantation

Since the administration of cyclophosphamide and busulfan can cause hemorrhagic cystitis and changes in urothelial cells, an investigation was carried out to see whether patients undergoing bone marrow transplantation (BMT) who were treated with these drugs showed such urothelial changes and whether exfoliative urinary cytology can contribute to the early diagnosis and monitoring of such changes. Morphologic and morphometric analyses were performed on cytocentrifuged, Papanicolaou-stained preparations of 700 samples from 107 patients. Various degrees of urothelial cell changes were found in 30.8% of the cases. These changes consisted mainly of a considerable increase in the size of the nucleus and of a cytoplasm that was often bizarrely shaped. Even the structures of the nucleus and the cytoplasm changed. The results of this study showed that exfoliative urinary cytology permits an early diagnosis and monitoring of urothelial cell changes related to the administration of busulfan and cyclophosphamide in connection with BMT.