A 3D system to model human pancreas development and its reference single-cell transcriptome atlas identify signaling pathways required for progenitor expansion

in Nature Communications (2021)

Coulomb interactions between dipolar quantum fluctuations in van der Waals bound molecules and materials

in Nature Communications (2021), 12(1), 137

Mutual Coulomb interactions between electrons lead to a plethora of interesting physical and chemical effects, especially if those interactions involve many fluctuating electrons over large spatial scales ... [more ▼]

Mutual Coulomb interactions between electrons lead to a plethora of interesting physical and chemical effects, especially if those interactions involve many fluctuating electrons over large spatial scales. Here, we identify and study in detail the Coulomb interaction between dipolar quantum fluctuations in the context of van der Waals complexes and materials. Up to now, the interaction arising from the modification of the electron density due to quantum van der Waals interactions was considered to be vanishingly small. We demonstrate that in supramolecular systems and for molecules embedded in nanostructures, such contributions can amount to up to 6 kJ/mol and can even lead to qualitative changes in the long-range van der Waals interaction. Taking into account these broad implications, we advocate for the systematic assessment of so-called Dipole-Correlated Coulomb Singles in large molecular systems and discuss their relevance for explaining several recent puzzling experimental observations of collective behavior in nanostructured materials. [less ▲]

Common diseases alter the physiological age-related blood microRNA profile.

in Nature communications (2020), 11(1), 5958

Aging is a key risk factor for chronic diseases of the elderly. MicroRNAs regulate post-transcriptional gene silencing through base-pair binding on their target mRNAs. We identified nonlinear changes in ... [more ▼]

Aging is a key risk factor for chronic diseases of the elderly. MicroRNAs regulate post-transcriptional gene silencing through base-pair binding on their target mRNAs. We identified nonlinear changes in age-related microRNAs by analyzing whole blood from 1334 healthy individuals. We observed a larger influence of the age as compared to the sex and provide evidence for a shift to the 5' mature form of miRNAs in healthy aging. The addition of 3059 diseased patients uncovered pan-disease and disease-specific alterations in aging profiles. Disease biomarker sets for all diseases were different between young and old patients. Computational deconvolution of whole-blood miRNAs into blood cell types suggests that cell intrinsic gene expression changes may impart greater significance than cell abundance changes to the whole blood miRNA profile. Altogether, these data provide a foundation for understanding the relationship between healthy aging and disease, and for the development of age-specific disease biomarkers. [less ▲]

Developmental GABA polarity switch and neuronal plasticity in Bioengineered Neuronal Organoids

in Nature Communications (2020), 11(1), 3791

Event-related functional MRI of awake behaving pigeons at 7T

in Nature Communications (2020), 11(1),

The atypical chemokine receptor ACKR3/CXCR7 is a broad-spectrum scavenger for opioid peptides.

in Nature communications (2020), 11(1), 3033

Endogenous opioid peptides and prescription opioid drugs modulate pain, anxiety and stress by activating opioid receptors, currently classified into four subtypes. Here we demonstrate that ACKR3/CXCR7 ... [more ▼]

Endogenous opioid peptides and prescription opioid drugs modulate pain, anxiety and stress by activating opioid receptors, currently classified into four subtypes. Here we demonstrate that ACKR3/CXCR7, hitherto known as an atypical scavenger receptor for chemokines, is a broad-spectrum scavenger of opioid peptides. Phylogenetically, ACKR3 is intermediate between chemokine and opioid receptors and is present in various brain regions together with classical opioid receptors. Functionally, ACKR3 is a scavenger receptor for a wide variety of opioid peptides, especially enkephalins and dynorphins, reducing their availability for the classical opioid receptors. ACKR3 is not modulated by prescription opioids, but we show that an ACKR3-selective subnanomolar competitor peptide, LIH383, can restrain ACKR3's negative regulatory function on opioid peptides in rat brain and potentiate their activity towards classical receptors, which may open alternative therapeutic avenues for opioid-related disorders. Altogether, our results reveal that ACKR3 is an atypical opioid receptor with cross-family ligand selectivity. [less ▲]

From quantum to continuum mechanics in the delamination of atomically-thin layers from substrates

in Nature Communications (2020)

A three-order-parameter bistable magnetoelectric multiferroic metal

in Nature Communications (2020)

Data driven discovery of cyber physical systems

in Nature Communications (2019)

Cyber-physical systems embed software into the physical world. They appear in a wide range of applications such as smart grids, robotics, and intelligent manufacturing. Cyber-physical systems have proved ... [more ▼]

Cyber-physical systems embed software into the physical world. They appear in a wide range of applications such as smart grids, robotics, and intelligent manufacturing. Cyber-physical systems have proved resistant to modeling due to their intrinsic complexity arising from the combination of physical and cyber components and the interaction between them. This study proposes a general framework for discovering cyber-physical systems directly from data. The framework involves the identification of physical systems as well as the inference of transition logics. It has been applied successfully to a number of real-world examples. The novel framework seeks to understand the underlying mechanism of cyber-physical systems as well as make predictions concerning their state trajectories based on the discovered models. Such information has been proven essential for the assessment of the performance of cyber- physical systems; it can potentially help debug in the implementation procedure and guide the redesign to achieve the required performance. [less ▲]

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 ▲]