Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19

in Nature Communications (2022), 13

COVID-19 is primarily known as a respiratory disease caused by SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, severe headaches, and even stroke are reported in up to 30 ... [more ▼]

COVID-19 is primarily known as a respiratory disease caused by SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, severe headaches, and even stroke are reported in up to 30% of cases and can persist even after the infection is over (long COVID). These neurological symptoms are thought to be produced by the virus infecting the central nervous system, however we don’t understand the molecular mechanisms triggering them. The neurological effects of COVID-19 share similarities to neurodegenerative diseases in which the presence of cytotoxic aggregated amyloid protein or peptides is a common feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we identified two peptides from the SARS-CoV-2 proteome that self-assemble into amyloid assemblies. Furthermore, these amyloids were shown to be highly toxic to neuronal cells. We suggest that cytotoxic aggregates of SARS-CoV-2 proteins may trigger neurological symptoms in COVID-19. [less ▲]

The mouse metallomic landscape of aging and metabolism

in Nature Communications (2022), 13(607),

Emerging spin-phonon coupling through cross-talk of two magnetic sublattices

in NATURE COMMUNICATIONS (2022), 13(1), 443-7

Typically, magnetic phenomena result from the spontaneous order of the sublattices. Here, the cross-talk of two magnetic ions gives rise to an intrinsic, yet non-spontaneous ordering and manifests as ... [more ▼]

Typically, magnetic phenomena result from the spontaneous order of the sublattices. Here, the cross-talk of two magnetic ions gives rise to an intrinsic, yet non-spontaneous ordering and manifests as emergent strong spin-phonon coupling in SmFeO3. Many material properties such as superconductivity, magnetoresistance or magnetoelectricity emerge from the non-linear interactions of spins and lattice/phonons. Hence, an in-depth understanding of spin-phonon coupling is at the heart of these properties. While most examples deal with one magnetic lattice only, the simultaneous presence of multiple magnetic orderings yield potentially unknown properties. We demonstrate a strong spin-phonon coupling in SmFeO3 that emerges from the interaction of both, iron and samarium spins. We probe this coupling as a remarkably large shift of phonon frequencies and the appearance of new phonons. The spin-phonon coupling is absent for the magnetic ordering of iron alone but emerges with the additional ordering of the samarium spins. Intriguingly, this ordering is not spontaneous but induced by the iron magnetism. Our findings show an emergent phenomenon from the non-linear interaction by multiple orders, which do not need to occur spontaneously. This allows for a conceptually different approach in the search for yet unknown properties. [less ▲]

The role of lattice dynamics in ferroelectric switching

in Nature Communications (2022)

Interactions between large molecules pose a puzzle for reference quantum mechanical methods

in Nature Communications (2021)

A computer-guided design tool to increase the efficiency of cellular conversions

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 ▲]

Loss of Ambra1 promotes melanoma growth and invasion.

in Nature communications (2021), 12(1), 2550

Melanoma is the deadliest skin cancer. Despite improvements in the understanding of the molecular mechanisms underlying melanoma biology and in defining new curative strategies, the therapeutic needs for ... [more ▼]

Melanoma is the deadliest skin cancer. Despite improvements in the understanding of the molecular mechanisms underlying melanoma biology and in defining new curative strategies, the therapeutic needs for this disease have not yet been fulfilled. Herein, we provide evidence that the Activating Molecule in Beclin-1-Regulated Autophagy (Ambra1) contributes to melanoma development. Indeed, we show that Ambra1 deficiency confers accelerated tumor growth and decreased overall survival in Braf/Pten-mutated mouse models of melanoma. Also, we demonstrate that Ambra1 deletion promotes melanoma aggressiveness and metastasis by increasing cell motility/invasion and activating an EMT-like process. Moreover, we show that Ambra1 deficiency in melanoma impacts extracellular matrix remodeling and induces hyperactivation of the focal adhesion kinase 1 (FAK1) signaling, whose inhibition is able to reduce cell invasion and melanoma growth. Overall, our findings identify a function for AMBRA1 as tumor suppressor in melanoma, proposing FAK1 inhibition as a therapeutic strategy for AMBRA1 low-expressing melanoma. [less ▲]

Integration of time-series meta-omics data reveals how microbial ecosystems respond to disturbance

in Nature Communications (2020)

The development of reliable, mixed-culture biotechnological processes hinges on understanding how microbial ecosystems respond to disturbances. Here we reveal extensive phenotypic plasticity and niche ... [more ▼]

The development of reliable, mixed-culture biotechnological processes hinges on understanding how microbial ecosystems respond to disturbances. Here we reveal extensive phenotypic plasticity and niche complementarity in oleaginous microbial populations from a biological wastewater treatment plant. We perform meta-omics analyses (metagenomics, metatranscriptomics, metaproteomics and metabolomics) on in situ samples over 14 months at weekly intervals. Based on 1,364 de novo metagenome-assembled genomes, we uncover four distinct fundamental niche types. Throughout the time-series, we observe a major, transient shift in community structure, coinciding with substrate availability changes. Functional omics data reveals extensive variation in gene expression and substrate usage amongst community members. Ex situ bioreactor experiments confirm that responses occur within five hours of a pulse disturbance, demonstrating rapid adaptation by specific populations. Our results show that community resistance and resilience are a function of phenotypic plasticity and niche complementarity, and set the foundation for future ecological engineering efforts. [less ▲]

Gene regulatory network inference from sparsely sampled noisy data

in Nature Communications (2020), 11

The complexity of biological systems is encoded in gene regulatory networks. Unravelling this intricate web is a fundamental step in understanding the mechanisms of life and eventually developing ... [more ▼]

The complexity of biological systems is encoded in gene regulatory networks. Unravelling this intricate web is a fundamental step in understanding the mechanisms of life and eventually developing efficient therapies to treat and cure diseases. The major obstacle in inferring gene regulatory networks is the lack of data. While time series data are nowadays widely available, they are typically noisy, with low sampling frequency and overall small number of samples. This paper develops a method called BINGO to specifically deal with these issues. Benchmarked with both real and simulated time-series data covering many different gene regulatory networks, BINGO clearly and consistently outperforms state-of-the-art methods. The novelty of BINGO lies in a nonparametric approach featuring statistical sampling of continuous gene expression profiles. BINGO’s superior performance and ease of use, even by non-specialists, make gene regulatory network inference available to any researcher, helping to decipher the complex mechanisms of life. [less ▲]