Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes.

Background: Array-comparative genomic hybridization (array-CGH) is a widely used technique to detect copy number variants (CNVs) associated with developmental delay/intellectual disability (DD/ID).

Aims: Identification of genomic disorders in DD/ID.

Materials And Methods: We performed a comprehensive array-CGH investigation of 1,015 consecutive cases with DD/ID and combined literature mining, genetic evidence, evolutionary constraint scores, and functional information in order to assess the pathogenicity of the CNVs.

Protein malnutrition attenuates bone anabolic response to PTH in female rats.

PTH is indicated for the treatment of severe osteoporosis. Elderly osteoporotic patients frequently suffer from protein malnutrition, which may contribute to bone loss. It is unknown whether this malnutrition may affect the response to PTH.

Systemic treatment with strontium ranelate accelerates the filling of a bone defect and improves the material level properties of the healing bone.

Rapid bone defect filling with normal bone is a challenge in orthopaedics and dentistry. Strontium ranelate (SrRan) has been shown to in vitro decrease bone resorption and increase bone formation, and represents a potential agent with the capacity to accelerate bone defect filling. In this study, bone tibial defects of 2.

External mechanical microstimuli modulate the osseointegration of titanium implants in rat tibiae.

Purpose: To assess the effect of external mechanical microstimuli of controlled magnitude on the microarchitecture of the peri-implant bone beds in rat tibiae.

Materials And Methods: Tibiae of forty rats were fitted with two transcutaneous titanium cylinders. After healing, the implants were loaded to 1 to 3 N, five days/week for four weeks.

Implementation of the "loaded implant" model in the rat using a miniaturized setup--description of the method and first results.

Objective: To miniaturize the "loaded implant" model to permit its application to small rodents. In this model, two titanium implants are placed 8 mm apart with their heads protruding from the skin and are forced together by a dedicated actuator. To assess the effect of (i) the post-implantation healing period and the duration of stimulation and (ii) the intratissular strain level on the microtomographical bone parameters BV/TV, Tb.

Hedgehog pathway activity is required for the lethality and intestinal phenotypes of mice with hyperactive Wnt signaling.

Several lines of evidence point to the central role of WNT signaling in the initiation of intestinal tumorigenesis, most often due to loss of APC, a negative regulator of the WNT-betaCATENIN/TCF pathway. Modeling human colon cancers in mice through loss of Apc has shown that inappropriate activation of Wnt signaling is sufficient to induce adenoma formation. More recent analyses have also demonstrated a key role for HEDGEHOG-GLI (HH-GLI) signaling in human colon cancers.

Hox gene function in vertebrate gut morphogenesis: the case of the caecum.

The digestive tract is made of different subdivisions with various functions. During embryonic development, the developing intestine expresses combinations of Hox genes along its anterior to posterior axis, suggesting a role for these genes in this regionalization process. In particular, the transition from small to large intestine is labelled by the transcription of all Hoxd genes except Hoxd12 and Hoxd13, the latter two genes being transcribed only near the anus.

Interactions between HOXD and Gli3 genes control the limb apical ectodermal ridge via Fgf10.

The development of the vertebrate limb is dependent upon two signaling centers, the apical ectodermal ridge (AER), which provides the underlying mesenchyme with essential growth factors, and the zone of polarizing activity (ZPA), the source of the Sonic hedgehog (SHH) product. Recent work involving gain and loss of function of Hox genes has emphasized their impact both on AER maintenance and Shh transcriptional activation. Here, we describe antagonistic interactions between posterior Hoxd genes and Gli3, suggesting that the latter product protects the AER from the deleterious effect of the formers, and we present evidence that Fgf10 is the mediator of HOX-dependent AER expansion.