Analysis of serum insulin-like growth factor binding proteins using western blotting: use of the method for titration of the binding proteins and competitive binding studies

A nitrocellulose gel transfer technique has been adapted to study the insulin-like growth factor (IGF) binding proteins of human serum. Normal and hypopituitary sera were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by electroblotting to nitrocellulose or nylon membrane. Nonidet-P40 (3%) and Tween 20 (0.1%) were required for quenching and to allow detection of the IGF binding proteins by autoradiography after overlay with either 125I-labeled IGF I or IGF II. Several forms of IGF binding protein have been identified with molecular weights of 41,500, 38,500, 34,000, 30,000, and 24,000. Titration and competitive binding studies with IGF were performed on the transferred IGF binding proteins, indicating that binding proteins isolated by this technique can be characterized.     

Familial Site-specific Ovarian Cancer Is Linked to BRCA1 on 17q12-21

In a study of nine families with “site-specific” ovarian cancer (criterion: three or more cases of epithelial ovarian cancer and no cases of breast cancer diagnosed at age <50 years) we have obtained evidence of linkage to the breast-ovarian cancer susceptibility gene, BRCA1 on 17q12-21. If the risk of cancer in these families is assumed to be restricted to the ovary, the best estimate of the proportion of families linked to BRCA1 is .78 (95% confidence interval .32–1.0). If predisposition to both breast and ovarian cancer is assumed, the proportion linked is 1.0 (95% confidence interval .46–1.0). The linkage of familial site-specific ovarian cancer to BRCA1 indicates the possibility of predictive testing in such families; however, this is only appropriate in families where the evidence for linkage to BRCA1 is conclusive.     

The role of biogeography in shaping diversity of the intestinal microbiota in house mice

The microbial communities inhabiting the mammalian intestinal tract play an important role in diverse aspects of host biology. However, little is known regarding the forces shaping variation in these communities and their influence on host fitness. To shed light on the contributions of host genetics, transmission and geography to diversity in microbial communities between individuals, we performed a survey of intestinal microbial communities in a panel of 121 house mice derived from eight locations across Western Europe using pyrosequencing of the bacterial 16S rRNA gene. The host factors studied included population structure estimated by microsatellite loci and mitochondrial DNA, genetic distance and geography. To determine whether host tissue (mucosa)‐associated communities display properties distinct from those of the lumen, both the caecal mucosa and contents were examined. We identified Bacteroides, Robinsoniella and Helicobacter as the most abundant genera in both the caecal content and mucosa‐associated communities of wild house mice. Overall, we found geography to be the most significant factor explaining patterns of diversity in the intestinal microbiota, with a comparatively weaker influence of host population structure and genetic distance. Furthermore, the influence of host genetic distance was limited to the mucosa communities, consistent with this environment being more intimately coupled to the host.     

A sharp incisor tool for predator house mice back to the wild

The house mouse (Mus musculus domesticus), as a successful invasive species worldwide, has to forage a variety of resources. Subantarctic mice display among the most notable diet shift from the usual omnivorous–granivorous diet, relying on a larger proportion of terrestrial animal prey. In agreement, a recent study of their mandible morphology evidenced an evolution of their mandible shape to optimize incisor biting and hence seize preys. Here, the incisors themselves are the focus of a morphometric analysis combined with a 3D study of their internal structure, aiming at a comparison between subantarctic populations (Guillou island, Kerguelen archipelago) with a range of western European continental, commensal mice. The predatory foraging behavior of Guillou mice was indeed associated with a sharper bevel of the lower incisor, which appears as an efficient morphology for piercing prey. The incisor of these mice also displays a reduced pulp cavity, suggesting slower eruption counterbalancing a reduced abrasion on such soft food material. The dynamics of the ever‐growing incisor may thus allow adaptive incisor sculpting and participate to the success of mice in foraging diverse resources.     

Alteration of cardiovascular and neuronal function in M1 knockout mice

We used gene targeting to generate mice lacking the M1 muscarinic acetylcholine receptor. These mice exhibit a decreased susceptibility to pilocarpine-induced seizures, loss of regulation of M-current potassium channel activity and of a specific calcium channel pathway in sympathetic neurons, a loss of the positive chronotropic and inotropic responses to the novel muscarinic agonist McN-A-343, and impaired learning in a hippocampal-dependent test of spatial memory.     

Evidence of a link between demographic rates and species habitat suitability from post release movements in a reinforced bird population

Despite the increasing use of species distribution models for predicting current or future animal distribution, only a few studies have linked the gradient of habitat suitability (HS) to demographic parameters. While such approaches can improve the reliability of models, they can help to better predict the response of species to changes in HS over space and time, as induced by ongoing global change. Here, we tested whether the spatial variation in HS along the individual movement path is related to survival, using extensive tracking data collected from captive‐bred individuals translocated to reinforce the wild populations of houbara bustard. We first modelled and mapped the HS from presence data of wild individuals using niche models in a consensus framework. We further analysed survival of released individuals using capture–recapture modelling and its links to HS, as the trend in suitability from the release sites along movements. We found that the survival of released individuals was related to changes in HS along their movements. For instance, individuals which moved to sites of lower HS than their release sites have lower survival probabilities than the others, independently of the HS of the release sites and daily movement rate. Our results provide an empirical support of the relationship between HS and survival, a major fitness component.     

Multi-parameter automodels and their applications

Motivated by the modelling of non-Gaussian data or positivelycorrelated data on a lattice, extensions of Besag's automodelsto exponential families with multi-dimensional parameters havebeen proposed recently. We provide a multiple-parameter analogueof Besag's one-dimensional result that gives the necessary formof the exponential families for the Markov random field's conditionaldistributions. We propose estimation of parameters by maximumpseudolikelihood and give a proof of the consistency of theestimators for the multi-parameter automodel. The methodologyis illustrated with examples, in particular the building ofa cooperative system with beta conditional distributions. Wealso indicate future applications of these models to the analysisof mixed-state spatial data.     

The “bone morphogenic proteins” pathways in bone and joint diseases: Translational perspectives from physiopathology to therapeutic targets

A large body of evidence supports an important role of bone morphogenic proteins (BMPs) pathways in skeletal development in the embryo. BMPs are also involved in skeletal homeostasis and diseases in the adult. They were first identified as major bone anabolic agents and recent advances indicate that they also regulate osteoclastogenesis and joint components via multiple cross-talks with other signaling pathways. This review attempts to integrate these data in the pathogenesis of bone and joints diseases, such as osteoporosis, fracture healing, osteoarthritis, inflammatory arthritis, or bone metastasis. The use of recombinant BMPs in bone tissue engineering and in the treatment of skeletal diseases, or future therapeutic strategies targeting BMPs signal and its regulators, will be discussed based on these considerations.     

New mechanism of BRCA-1 mutation by deletion/insertion at the same nucleotide position in three unrelated French breast/ovarian cancer families

A novel complex mutation consisting of a small deletion/insertion (3958del5ins4) was found in the breast cancer-1 gene (BRCA-1) in three unrelated French breast and/or ovarian cancer families. These mutations occurred at the same nucleotide position of the 3′ end of exon 11. The wild-type sequence, CTCAG, was deleted and replaced by AGGC in the three families. The consequence is the generation of a stop codon, TAG, resulting in a truncated protein. We propose two different mechanisms to explain the generation of this complex mutation: (i) the simultaneous occurrence of a deletion and an insertion in a stem-loop structure and (ii) the abortive integration of a human transposable element (Tigger 1) that deleted 5 nucleotides and inserted a 4-nucleotide “scar”, corresponding to the 5′ extremity of the transposon. Received: 26 November 1997 / Accepted: 6 February 1998     

Power and Sample Size Determination in the Rasch Model: Evaluation of the Robustness of a Numerical Method to Non-Normality of the Latent Trait

Patient-reported outcomes (PRO) have gained importance in clinical and epidemiological research and aim at assessing quality of life, anxiety or fatigue for instance. Item Response Theory (IRT) models are increasingly used to validate and analyse PRO. Such models relate observed variables to a latent variable (unobservable variable) which is commonly assumed to be normally distributed. A priori sample size determination is important to obtain adequately powered studies to determine clinically important changes in PRO. In previous developments, the Raschpower method has been proposed for the determination of the power of the test of group effect for the comparison of PRO in cross-sectional studies with an IRT model, the Rasch model. The objective of this work was to evaluate the robustness of this method (which assumes a normal distribution for the latent variable) to violations of distributional assumption. The statistical power of the test of group effect was estimated by the empirical rejection rate in data sets simulated using a non-normally distributed latent variable. It was compared to the power obtained with the Raschpower method. In both cases, the data were analyzed using a latent regression Rasch model including a binary covariate for group effect. For all situations, both methods gave comparable results whatever the deviations from the model assumptions. Given the results, the Raschpower method seems to be robust to the non-normality of the latent trait for determining the power of the test of group effect.