Biomimetic mineralization of metal-organic frameworks as protective coatings for biomacromolecules

Enhancing the robustness of functional biomacromolecules is a critical challenge in biotechnology, which if addressed would enhance their use in pharmaceuticals, chemical processing and biostorage. Here we report a novel method, inspired by natural biomineralization processes, which provides unprecedented protection of biomacromolecules by encapsulating them within a class of porous materials termed metal-organic frameworks. We show that proteins, enzymes and DNA rapidly induce the formation of protective metal-organic framework coatings under physiological conditions by concentrating the framework building blocks and facilitating crystallization around the biomacromolecules. The resulting biocomposite is stable under conditions that would normally decompose many biological macromolecules. For example, urease and horseradish peroxidase protected within a metal-organic framework shell are found to retain bioactivity after being treated at 80 °C and boiled in dimethylformamide (153 °C), respectively. This rapid, low-cost biomimetic mineralization process gives rise to new possibilities for the exploitation of biomacromolecules.Kang Liang, Raffaele Ricco, Cara M. Doherty, Mark J. Styles, Stephen Bell, Nigel Kirby, Stephen Mudie, David Haylock, Anita J. Hill, Christian J. Doonan, Paolo Falcar

A new form of childhood onset, autosomal recessive spinocerebellar ataxia and epilepsy is localized at 16q21-q23.

Childhood ataxias are a complex set of inherited disorders. Ataxias associated with generalized tonic-clonic epilepsy are usually included with the progressive myoclonus epilepsies (PME). Five disease entities, Unverricht-Lundborg disease, Lafora's disease, neuronal ceroid lipofuscinoses, myoclonic epilepsy with ragged red fibres and sialidoses, account for the majority of PME cases. Two rare forms of ataxia plus epilepsy, sensory ataxic neuropathy, dysarthria and ophthalmoparesis, and infantile onset spinocerebellar ataxia were described recently and found to be caused by defective mitochondrial proteins. We report here a large consanguineous family from Saudi Arabia with four affected children presenting with generalized tonic-clonic epilepsy, ataxia and mental retardation, but neither myoclonus nor mental deterioration. MRI and muscle biopsy of one patient revealed, respectively, posterior white matter hyperintensities and vacuolization of the sarcotubular system. We localized the defective gene by homozygosity mapping to a 19 Mb interval in 16q21-q23 between markers D16S3091 and D16S3050. Linkage studies in this region will allow testing for homogeneity of this novel ataxia-epilepsy entity

A spray-drying strategy for synthesis of nanoscale metal-organic frameworks and their assembly into hollow superstructures

Metal-organic frameworks (MOFs) are among the most attractive porous materials known today. Their miniaturization to the nanoscale-into nanoMOFs-is expected to serve myriad applications from drug delivery to membranes, to open up novel avenues to more traditional storage and catalysis applications, and to enable the creation of sophisticated superstructures. Here, we report the use of spray-drying as a versatile methodology to assemble nanoMOFs, yielding spherical hollow superstructures with diameters smaller than 5 μm. This strategy conceptually mimics the emulsions used by chemists to confine the synthesis of materials, but does not require secondary immiscible solvents or surfactants. We demonstrate that the resulting spherical, hollow superstructures can be processed into stable colloids, whose disassembly by sonication affords discrete, homogeneous nanoMOFs. This spray-drying strategy enables the construction of multicomponent MOF superstructures, and the encapsulation of guest species within these superstructures. We anticipate that this will provide new routes to capsules, reactors and composite materials. © 2013 Macmillan Publishers Limited. All rights reserved.I.I. and M.C.S. thank MICINN and ICN for a Ramón y Cajal grant and a research contract, respectively. A.C. thanks the Generalitat de Catalunya for a FI fellowship.Peer Reviewe

Localization of a Recessive Gene for North American Indian Childhood Cirrhosis to Chromosome Region 16q22—and Identification of a Shared Haplotype

North American Indian childhood cirrhosis (NAIC, or CIRH1A) is an isolated nonsyndromic form of familial cholestasis reported in Ojibway-Cree children and young adults in northwestern Quebec. The pattern of transmission is consistent with an autosomal recessive mode of inheritance. To map the NAIC locus, we performed a genomewide scan on three DNA pools of samples from 13 patients, 16 unaffected siblings, and 22 parents from five families. Analysis of 333 highly polymorphic markers revealed 3 markers with apparent excess allele sharing among affected individuals. Additional mapping identified a chromosome 16q segment shared by all affected individuals. When the program FASTLINK/LINKAGE was used and a completely penetrant autosomal recessive mode of inheritance was assumed, a maximum LOD score of 4.44 was observed for a recombination fraction of 0, with marker D16S3067. A five-marker haplotype (D16S3067, D16S752, D16S2624, D16S3025, and D16S3106) spanning 4.9 cM was shared by all patients. These results provide significant evidence of linkage for a candidate gene on chromosome 16q22