New recessive truncating mutation in LTBP3 in a family with oligodontia, short stature, and mitral valve prolapse.

Latent TGFB-binding protein 3 (LTBP3) is known to increase bio-availability of TGFB. A homozygous mutation in this gene has previously been associated with oligodontia and short stature in a single family. We report on two sisters with homozygous truncating mutations in LTBP3. In addition to oligodontia and short stature, both sisters have mitral valve prolapse, suggesting a link between truncating LTBP3 mutations and mitral valve disease mediated through the TGFB pathway.

Inverse Miniemulsion Enables the Continuous-Flow Synthesis of Controlled Ultra-High Molecular Weight Polymers.

We report the controlled synthesis of ultra-high molecular weight (UHMW) polymers (Mn ≥ 106 g/mol) via continuous flow in a tubular reactor. At high monomer conversion, UHMW polymers in homogeneous batch polymerization exhibit high viscosities that pose challenges for employing continuous flow reactors. However, under heterogeneous inverse miniemulsion (IME) conditions, UHMW polymers can be produced within the dispersed phase, while the viscosity of the heterogeneous mixture remains approximately the same as the viscosity of the continuous phase. Conducting such IME polymerizations in flow results in a faster rate of polymerization compared to batch IME polymerizations while still providing excellent control over molecular weight up to 106 g/mol. Crucial emulsion parameters, such as particle size and stability under continuous flow conditions, were examined using dynamic light scattering. A range of poly(N,N-dimethylacrylamide) and poly(4-acryloylmorpholine) polymers with molecular weights of 104-106 g/mol (D ≤ 1.31) were produced by this method using water-soluble trithiocarbonates as photoiniferters.

Enlightening advances in polymer bioconjugate chemistry: light-based techniques for grafting to and from biomacromolecules.

Photochemistry has revolutionized the field of polymer-biomacromolecule conjugation. Ligation reactions necessitate biologically benign conditions, and photons have a significant energy advantage over what is available thermally at ambient temperature, allowing for rapid and unique reactivity. Photochemical reactions also afford many degrees of control, specifically, spatio-temporal control, light source tunability, and increased oxygen tolerance. Light-initiated polymerizations, in particular photo-atom-transfer radical polymerization (photo-ATRP) and photoinduced electron/energy transfer reversible addition-fragmentation chain transfer polymerization (PET-RAFT), have been used for grafting from proteins, DNA, and cells. Additionally, the spatio-temporal control inherent to light-mediated chemistry has been utilized for grafting biomolecules to hydrogel networks for many applications, such as 3-D cell culture. While photopolymerization has clear advantages, there are factors that require careful consideration in order to obtain optimal control. These factors include the photocatalyst system, light intensity, and wavelength. This Perspective aims to discuss recent advances of photochemistry for polymer biomacromolecule conjugation and potential considerations while tailoring these systems.

Miscanthus Giganteus: A commercially viable sustainable source of cellulose nanocrystals.

With a goal of identifying a new scalable source for cellulose nanocrystals (CNCs), we successfully isolated CNCs from a sustainable, non-invasive grass, Miscanthus x. Giganteus (MxG). Subjecting MxG stalks to base hydrolysis, bleaching and acid hydrolysis allowed access to cellulose nanocrystals (MxG-CNC) in high yields. X-ray diffraction studies showed the crystallinity of the MxG-CNCs increased with subsequent treatment conditions (>90% after HCl hydrolysis). Transmission electron microscopy showed that the MxG-CNC exhibit relatively high aspect ratios (60-70), and small angle neutron scattering showed the crystals were ribbon-like with a width and thickness of 8.5 and 2.8nm respectively. As expected, thermomechanical analysis of nanocomposites fabricated with carboxylic acid functionalized MxG-CNC (MxG-CNC-COOH) and PVAc showed an increase in modulus (above Tg) as filler content was increased. Comparing the properties to PVAc nanocomposites containing CNCs from wood showed at least as good, if not slightly better, reinforcement at the same loading level.

Spondyloepiphyseal dysplasias and bilateral legg-calvé-perthes disease: diagnostic considerations for mucopolysaccharidoses.

Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome, MIM 253200 ) is an autosomal recessive lysosomal storage disease (LSD) caused by decreased activity of arylsulfatase B (N-acetylgalactosamine 4-sulfatase) enzyme resulting in dermatan sulfate accumulation; mucopolysaccharidosis type IVA (MPS IVA, Morquio syndrome A, MIM 253000 ) by decreased activity of N-acetylgalactosamine 6-sulfatase enzyme resulting in accumulation of keratan sulfate. Clinical symptoms include coarse facial features, joint stiffness, hepatosplenomegaly, hip osteonecrosis, and dysostosis multiplex. MPS IVA symptoms are similar but with joint hypermobility.With suspicion of MPS disease, clinicians request urine studies for quantitative and qualitative glycosaminoglycans (GAGs). Diagnosis is confirmed by decreased enzyme activity in leukocytes or cultured skin fibroblasts. Further confirmation is obtained with identification of two mutations in the ARSB gene for MPS VI or mutations in the GALNS gene for MPS IVA.We report slowly progressing patients, one with MPS VI and two with MPS IVA, who presented with skeletal changes and hip findings resembling Legg-Calvé-Perthes disease or spondyloepiphyseal dysplasia and normal/near normal urine GAG levels. The urine analysis data presented suggest that present screening techniques for MPS are inadequate in milder patients and result in delayed or missed diagnoses. The patients presented in this paper emphasize the importance of enzymatic and molecular testing.