High-resolution
synchrotron X-ray powder diffraction (XRD) combined
with the Rietveld refinement method and confocal laser scanning microscopy
(CLSM) were utilized in this study to elucidate the interaction between
a recombinant biomineralization protein (perlucin) fused to green
fluorescent protein (GFP) and synthetic calcite. Although recombinant
perlucin is insoluble, its solubility was increased via fusion to
the highly soluble GFP. We demonstrate that GFP-perlucin derivatives
become incorporated into the calcite structure and induce concentration-dependent
anisotropic lattice distortions along the host’s c-axis. In contrast, GFP alone is hardly incorporated at all. The
observed lattice distortions and peculiar microstructure of the crystals
are comparable to those previously observed in biogenic calcite. Taking
advantage of biotechnology to optimize individual protein properties,
such as the solubility of an otherwise insoluble protein derivative,
is a promising route toward the synthesis of new and improved biocomposite
materials.
We aimed to unravel the molecular genetic basis of inherited retinal degeneration (IRD) in a comprehensive cohort of patients diagnosed in the largest center for IRD in Germany. A cohort of 2,158 affected patients from 1,785 families diagnosed with IRD was analyzed by targeted next‐generation sequencing (NGS). Patients with single‐gene disorders (i.e., choroideremia and retinoschisis) were analyzed by Sanger sequencing and multiplex ligation‐dependent probe amplification. Our study cohort accounts for ∼7% of the estimated 30,000 patients with IRD in Germany, thereby providing representative data for both the prevalence of IRDs and the mutation spectrum of IRD genes for the population in Germany. We achieved a molecular diagnostic rate of 35–95%, depending on the clinical entities, with a high detection rate for achromatopsia, retinoschisis, and choroideremia, and a low detection rate for central areolar choroidal dystrophy and macular dystrophy. A total of 1,161 distinct variants were identified, including 501 novel variants, reaffirming the known vast genetic heterogeneity of IRD in a mainly outbred European population. This study demonstrates the clinical utility of panel‐based NGS in a large and highly heterogeneous cohort from an outbred population and for the first time gives a comprehensive representation of the genetic landscape of IRDs in Germany. The data are valuable and crucial for the scientific community and healthcare providers, but also for the pharmaceutical industry in the progressing field of personalized medicine and gene therapy.
Many crystals in nature exhibit fascinating mechanical, optical, magnetic and other characteristics. One of the reasons for this phenomenon has to do with the presence of specific organic molecules that are tightly associated with the mineral. Over the years, some organic crystals have been found to be located within the lattices of their singlecrystalline biogenic hosts. A number of questions remain unanswered: for example, how do these molecules become incorporated and what is their function? In this review we survey the gradual refinement of the above mentioned finding in biogenic crystals, with the object of tracing the acquisition of our fundamental knowledge in this field during the last 50 years. We highlight the progress made in understanding the function and significance of this intracrystalline organic matter, from the earliest observations of this phenomenon in a biological system to the highly promising recent achievements in bio-inspired material synthesis, where intracrystalline molecules have been used in many studies to synthesize numerous synthetic nanohybrid composites with fascinating new properties.Boaz Pokroy is an associate professor in the Department of Materials Science and Engineering at the Technion-Israel Institute of Technology, Israel, where he earned all of his degrees. Previously, he was a postdoctoral fellow and Fulbright Scholar in the laboratory of Prof. Joanna Aizenberg at the School of Engineering and Applied Sciences at Harvard University and Bell Labs. Pokroy's research focuses on biomineralization and bio-inspired surface engineering. He studies the structure of biominerals on the atomic, nano-, and mesoscales using state-of-the-art high-resolution characterization techniques such as high-resolution synchrotron diffraction and aberration-corrected transmission electron microscopy. Based on the strategies that organisms use to produce natural materials, his lab also develops novel bio-inspired materials, such as semiconductors whose bandgap can be tuned by the incorporation of intracrystalline biological molecules; controlling the short-range order of nano-amorphous materials; and fabrication of superhydrophobic/superoleophobic surfaces for various applications.
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