The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions.
A versatile method for synthesizing functionalized amorphous degradable polyesters via step growth
polycondensation was investigated. A series of dicarboxylic acids and anhydrides were synthesized by Diels−Alder reactions of fumaric acid and maleic anhydride, respectively, with various dienes. The resulting difunctional
monomers were reacted with 1,8-octanediol in the presence of tin octanoate catalyst at 160 °C and 30 mmHg for
24 h to form new unsaturated aliphatic polyesters. Each polyester had molecular weight 〈M
n〉 between 1.0 × 104
and 2.0 × 104 g mol-1 and a polydispersity index near 2.0. All of the materials were amorphous and had glass
transition temperatures between −30 and −15 °C. Each polymer repeat unit necessarily featured a double bond,
which was exploited to cross-link the materials yielding degradable elastomers. Amine- and ether-containing
polyesters were synthesized by using monomers formed from the corresponding polar functionalized dienes.
Using this broad cycloaddition scheme, a variety of amorphous, functionalized polyesters were successfully
synthesized.
Materials capable of dynamically controlling surface chemistry and topography are highly desirable. We have designed a system that is uniquely able to remotely control the presented functionality and geometry at a given time by using a functionalizable shape memory material. This was accomplished by incorporating controlled amounts of an azide-containing monomer into a shape memory polymeric material. These materials are capable of physically changing surface geometry over a broad range of length scales from >1 mm to 100 nm. Using copper-assisted click chemistry, they can be functionalized with a variety of molecules to yield different surfaces. Combining these features gave materials that can change both the presented geometry and functionality at tunable transition temperatures.
A new class of thermoplastic poly(ester urethane)s containing novel soft segments are prepared using a one-step synthesis. Amorphous polyester prepolymers (〈M n 〉 ) 1.5 × 10 3 -3.4 × 10 3 g/mol) were incorporated as soft segments in poly(ester urethane)s using an aromatic diisocyanate, 4,4′-methylenebis(phenylisocyanate), but with no chain extension. These completely amorphous materials had a wide range of mechanical properties (E ) 0.86-29.3 MPa; γ max ) 2106%), and they possessed linear degradation profiles. A combination of contact angle studies, water uptake studies, and XPS analysis showed that these materials exhibited a surface segregation phenomenon upon contact with water. Kinetic analyses showed that three of the materials are among the fastest degrading poly(ester urethane)s reported in the literature to date. Initial cytotoxicity testing by minimum essential medium tests showed that only one of the nine new materials gave a cytotoxic response. Two separate sterilization methods did not elicit a cytotoxic response in the poly(ester urethane)s even after a 1 week incubation period.
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