Biallelic VARS variants cause developmental encephalopathy with microcephaly that is recapitulated in vars knockout zebrafish

in Nature Communications (2019), 10(1), 708

Aminoacyl tRNA synthetases (ARSs) link specific amino acids with their cognate transfer RNAs in a critical early step of protein translation. Mutations in ARSs have emerged as a cause of recessive, often ... [more ▼]

Aminoacyl tRNA synthetases (ARSs) link specific amino acids with their cognate transfer RNAs in a critical early step of protein translation. Mutations in ARSs have emerged as a cause of recessive, often complex neurological disease traits. Here we report an allelic series consisting of seven novel and two previously reported biallelic variants in valyl-tRNA synthetase (VARS) in ten patients with a developmental encephalopathy with microcephaly, often associated with early-onset epilepsy. In silico, in vitro, and yeast complementation assays demonstrate that the underlying pathomechanism of these mutations is most likely a loss of protein function. Zebrafish modeling accurately recapitulated some of the key neurological disease traits. These results provide both genetic and biological insights into neurodevelopmental disease and pave the way for further in-depth research on ARS related recessive disorders and precision therapies. [less ▲]

Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies

in Nature Communications (2018)

Optical control of polarization in ferroelectric heterostructures

in Nature Communications (2018), 9

In the ferroelectric devices, polarization control is usually accomplished by application of an electric field. In this paper, we demonstrate optically induced polarization switching in BaTiO3-based ... [more ▼]

In the ferroelectric devices, polarization control is usually accomplished by application of an electric field. In this paper, we demonstrate optically induced polarization switching in BaTiO3-based ferroelectric heterostructures utilizing a two-dimensional narrow-gap semiconductor MoS2 as a top electrode. This effect is attributed to the redistribution of the photo-generated carriers and screening charges at the MoS2/BaTiO3 interface. Specifically, a two-step process, which involves formation of intra-layer excitons during light absorption followed by their decay into inter-layer excitons, results in the positive charge accumulation at the interface forcing the polarization reversal from the upward to the downward direction. Theoretical modeling of the MoS2 optical absorption spectra with and without the applied electric field provides quantitative support for the proposed mechanism. It is suggested that the discovered effect is of general nature and should be observable in any heterostructure comprising a ferroelectric and a narrow gap semiconductor. [less ▲]

Tailoring van der Waals dispersion interactions with external electric charges

in Nature Communications (2018), 9

Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential

in Nature Communications (2018)

Competition between crystal and fibril formation in molecular mutations of amyloidogenic peptides

in Nature Communications (2017), 8

Amyloidogenic model peptides are invaluable for investigating assembly mechanisms in disease related amyloids and in protein folding. During aggregation, such peptides can undergo bifurcation leading to ... [more ▼]

Amyloidogenic model peptides are invaluable for investigating assembly mechanisms in disease related amyloids and in protein folding. During aggregation, such peptides can undergo bifurcation leading to fibrils or crystals, however the mechanisms of fibril-to-crystal conversion are unclear. We navigate herein the energy landscape of amyloidogenic peptides by studying a homologous series of hexapeptides found in animal, human and disease related proteins. We observe fibril-to-crystal conversion occurring within single aggregates via untwisting of twisted ribbon fibrils possessing saddle-like curvature and cross-sectional aspect ratios approaching unity. Changing sequence, pH or concentration shifts the growth towards larger aspect ratio species assembling into stable helical ribbons possessing mean-curvature. By comparing atomistic calculations of desolvation energies for association of peptides we parameterise a kinetic model, providing a physical explanation of fibril-to-crystal interconversion. These results shed light on the self-assembly of amyloidogenic peptides, suggesting amyloid crystals, not fibrils, represent the ground state of the protein folding energy landscape. [less ▲]

Nanoscale $\uppi$\textendash$\uppi$ stacked molecules are bound by collective charge fluctuations

in Nature Communications (2017), 8

Genome-wide analysis of chromosomal import patterns after natural 2 transformation of Helicobacter pylori

in Nature Communications (2016), 7

Recombination plays a dominant role in the evolution of the bacterial pathogen Helicobacter pylori, but its dynamics remain incompletely understood. Here we use an in vitro transformation system combined ... [more ▼]

Recombination plays a dominant role in the evolution of the bacterial pathogen Helicobacter pylori, but its dynamics remain incompletely understood. Here we use an in vitro transformation system combined with genome sequencing to study chromosomal integration patterns after natural transformation. A single transformation cycle results in up to 21 imports, and repeated transformations generate a maximum of 92 imports (8% sequence replacement). Import lengths show a bimodal distribution with averages of 28 and 1,645bp. Reanalysis of paired H. pylori genomes from chronically infected people demonstrates the same bimodal import pattern in vivo. Restriction endonucleases (REases) of the recipient bacteria fail to inhibit integration of homeologous DNA, independently of methylation. In contrast, REases limit the import of heterologous DNA. We conclude that restriction-modification systems inhibit the genomic integration of novel sequences, while they pose no barrier to homeologous recombination, which reconciles the observed stability of the H. pylori gene content and its highly recombinational population structure. [less ▲]

The Plasma Membrane Calcium ATPase 4 Signaling in Cardiac Fibroblasts Mediates Cardiomyocyte Hypertrophy

in Nature Communications (2016)

Ultrafast acousto-optic mode conversion in optically birefringent ferroelectrics

in NATURE COMMUNICATIONS (2016), 7

The ability to generate efficient giga-terahertz coherent acoustic phonons with femtosecond laser makes acousto-optics a promising candidate for ultrafast light processing, which faces electronic device ... [more ▼]

The ability to generate efficient giga-terahertz coherent acoustic phonons with femtosecond laser makes acousto-optics a promising candidate for ultrafast light processing, which faces electronic device limits intrinsic to complementary metal oxide semiconductor technology. Modern acousto-optic devices, including optical mode conversion process between ordinary and extraordinary light waves (and vice versa), remain limited to the megahertz range. Here, using coherent acoustic waves generated at tens of gigahertz frequency by a femtosecond laser pulse we reveal the mode conversion process and show its efficiency in ferroelectric materials such as BiFeO3 and LiNbO3. Further to the experimental evidence, we provide a complete theoretical support to this all-optical ultrafast mechanism mediated by acousto-optic interaction. By allowing the manipulation of light polarization with gigahertz coherent acoustic phonons, our results provide a novel route for the development of next-generation photonic-based devices and highlight new capabilities in using ferroelectrics in modern photonics. [less ▲]