The Effect of the Botulinum Toxin-A on Craniofacial Development: An Experimental Study.

Ann Plast Surg. 2009 Sep 4; Babuccu B, Babuccu O, Yurdakan G, Ankaral HIn this study, we developed a novel experimental model to evaluate muscular action on bone formation and remodeling by the help of Botulinum toxin-A (BTX).Forty-nine 15-day-old male Wistar rats were put into 4 groups randomly. Group 1 was the control group. BTX 0.4 IU (0.05 mL) was injected into the right masseter muscle in group 2 and into right temporalis muscle in group 3. The same volume of sterile saline was given into the both above-mentioned muscles in group 4. At the end of the fourth month, all animals were killed. Histology and weight of the masseter and temporalis muscles were studied. Thirty different osteometric measurements were also taken from skulls.Significant atrophy in BTX injected muscles was observed in groups 2 and 3. In group 4 (saline injection), only few osteometric measurements were significantly reduced, indicating the effect of the injection itself. Both groups 2 and 3 have apparent decrease in nasal bone, premaxilla, maxilla, and zygomatic dimensions on the injected side. When masseter group was compared with control and saline groups, no significant difference was found in skull base dimensions and mandibular length. In contrast, temporal group has also shown significant decrease in skull base dimensions.Our conclusions are as follows: (1) With this model, it is possible to study muscular action on bone formation and modeling without any surgical intervention, that is, by avoiding surgical artifacts, such as scar and contracture; (2) denervation of the skeletal muscles with BTX during the growing phase does effect bone development in a negative way; (3) pediatric use of the BTX deserves reevaluation under the light of these findings.

Recombination is suppressed over a large region of the rainbow trout Y chromosome.

Anim Genet. 2009 Sep 10; Phillips RB, Dekoning JJ, Ventura AB, Nichols KM, Drew RE, Chaves LD, Reed KM, Felip A, Thorgaard GHSummary The previous genetic mapping data have suggested that most of the rainbow trout sex chromosome pair is pseudoautosomal, with very small X-specific and Y-specific regions. We have prepared an updated genetic and cytogenetic map of the male rainbow trout sex linkage group. Selected sex-linked markers spanning the X chromosome of the female genetic map have been mapped cytogenetically in normal males and genetically in crosses between the OSU female clonal line and four different male clonal lines as well as in outcrosses involving outbred OSU and hybrids between the OSU line and the male clonal lines. The cytogenetic maps of the X and Y chromosomes were very similar to the female genetic map for the X chromosome. Five markers on the male maps are genetically very close to the sex determination locus (SEX), but more widely spaced on the female genetic map and on the cytogenetic map, indicating a large region of suppressed recombination on the Y chromosome surrounding the SEX locus. The male map is greatly extended at the telomere. A BAC clone containing the SCAR (sequence characterized amplified region) Omy-163 marker, which maps close to SEX, was subjected to shotgun sequencing. Two carbonyl reductase genes and a gene homologous to the vertebrate skeletal ryanodine receptor were identified. Carbonyl reductase is a key enzyme involved in production of trout ovarian maturation hormone. This brings the number of type I genes mapped to the sex chromosome to six and has allowed us to identify a region on zebrafish chromosome 10 and medaka chromosome 13 which may be homologous to the distal portion of the long arm of the rainbow trout Y chromosome.

Drosophila Cip4/Toca-1 Integrates Membrane Trafficking and Actin Dynamics through WASP and SCAR/WAVE.

Curr Biol. 2009 Aug 27; Fricke R, Gohl C, Dharmalingam E, Grevelhörster A, Zahedi B, Harden N, Kessels M, Qualmann B, Bogdan SBACKGROUND: Developmental processes are intimately tied to signaling events that integrate the dynamic reorganization of the actin cytoskeleton and membrane dynamics. The F-BAR-domain-containing proteins are prime candidates to couple actin dynamics and membrane trafficking in different morphogenetic processes. RESULTS: Here, we present the functional analysis of the Drosophila F-BAR protein Cip4/Toca1 (Cdc42-interacting protein 4/transducer of Cdc42-dependent actin assembly 1). Cip4 is able to form a complex with WASP and SCAR/WAVE and recruits both actin-nucleation-promoting factors to invaginating membranes and endocytic vesicles. Actin-comet-tail-based movement of these vesicles depends not only on WASP but largely on WAVE function. In vivo, loss of cip4 function causes multiple wing hairs. A similar phenotype is observed when vesicle scission is affected after Dynamin suppression. Gene dosage experiments show that Cip4 and WAVE functionally interact to restrict wing hair formation. Further rescue experiments confirm that Cip4 is able to act through WAVE and WASP in vivo. Biochemical and functional data support a model in which Cdc42 acts upstream of Cip4 and recruits not only WASP but also SCAR/WAVE via Abi to control Dynamin-dependent cell polarization in the wing. CONCLUSION: Cip4 integrates membrane trafficking and actin dynamics through WASP and WAVE. First, Cip4 promotes membrane invaginations and triggers the vesicle scission by recruiting Dynamin to the neck of nascent vesicles. Second, Cip4 recruits WASP and WAVE proteins to induce actin polymerization, supporting vesicle scission and providing the force for vesicle movement.

Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in Swine.

J Am Coll Cardiol. 2009 Sep 8; 54(11): 1014-23Leor J, Tuvia S, Guetta V, Manczur F, Castel D, Willenz U, Petneházy O, Landa N, Feinberg MS, Konen E, Goitein O, Tsur-Gang O, Shaul M, Klapper L, Cohen SOBJECTIVES: This study sought to determine whether alginate biomaterial can be delivered effectively into the infarcted myocardium by intracoronary injection to prevent left ventricular (LV) remodeling early after myocardial infarction (MI). BACKGROUND: Although injectable biomaterials can improve infarct healing and repair, the feasibility and effectiveness of intracoronary injection have not been studied. METHODS: We prepared a calcium cross-linked alginate solution that undergoes liquid to gel phase transition after deposition in infarcted myocardium. Anterior MI was induced in swine by transient balloon occlusion of left anterior descending coronary artery. At 4 days after MI, either alginate solution (2 or 4 ml) or saline was injected selectively into the infarct-related coronary artery. An additional group (n = 19) was treated with incremental volumes of biomaterial (1, 2, and 4 ml) or 2 ml saline and underwent serial echocardiography studies. RESULTS: Examination of hearts harvested after injection showed that the alginate crossed the infarcted leaky vessels and was deposited as hydrogel in the infarcted tissue. At 60 days, control swine experienced an increase in left ventricular (LV) diastolic area by 44%, LV systolic area by 45%, and LV mass by 35%. In contrast, intracoronary injection of alginate (2 and 4 ml) prevented and even reversed LV enlargement (p < 0.01). Post-mortem analysis showed that the biomaterial (2 ml) increased scar thickness by 53% compared with control (2.9 +/- 0.1 mm vs. 1.9 +/- 0.3 mm; p < 0.01) and was replaced by myofibroblasts and collagen. CONCLUSIONS: Intracoronary injection of alginate biomaterial is feasible, safe, and effective. Our findings suggest a new percutaneous intervention to improve infarct repair and prevent adverse remodeling after reperfused MI.