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),

Chiral structures of electric polarization vectors quantified by X-ray resonant scattering

in Nature Communications (2022)

Evolution of the murine gut resistome following broad-spectrum antibiotic treatment.

in Nature communications (2022), 13(1), 2296

The emergence and spread of antimicrobial resistance (AMR) represent an ever-growing healthcare challenge worldwide. Nevertheless, the mechanisms and timescales shaping this resistome remain elusive ... [more ▼]

The emergence and spread of antimicrobial resistance (AMR) represent an ever-growing healthcare challenge worldwide. Nevertheless, the mechanisms and timescales shaping this resistome remain elusive. Using an antibiotic cocktail administered to a murine model along with a longitudinal sampling strategy, we identify the mechanisms by which gut commensals acquire antimicrobial resistance genes (ARGs) after a single antibiotic course. While most of the resident bacterial populations are depleted due to the treatment, Akkermansia muciniphila and members of the Enterobacteriaceae, Enterococcaceae, and Lactobacillaceae families acquire resistance and remain recalcitrant. We identify specific genes conferring resistance against the antibiotics in the corresponding metagenome-assembled genomes (MAGs) and trace their origins within each genome. Here we show that, while mobile genetic elements (MGEs), including bacteriophages and plasmids, contribute to the spread of ARGs, integrons represent key factors mediating AMR in the antibiotic-treated mice. Our findings suggest that a single course of antibiotics alone may act as the selective sweep driving ARG acquisition and incidence in gut commensals over a single mammalian lifespan. [less ▲]

Deterministic control of ferroelectric polarization by ultrafast laser pulses

in Nature Communications (2022), 13

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 ▲]