Evolving mortality and clinical outcomes of hospitalized subjects during successive COVID-19 waves in Catalonia, Spain.

Background: The changes in shield strategies, treatments, emergence variants, and healthcare pathways might shift the profile and outcome of patients hospitalized with COVID-19 in successive waves of the outbreak.

Methods: We retrospectively analysed the characteristics and in-hospital outcomes of all patients admitted with COVID-19 in eight university hospitals of Catalonia (North-East Spain) between Feb 28, 2020 and Feb 28, 2021. Using a 7-joinpoint regression analysis, we split admissions into four waves.

Quantifying nucleoporin stoichiometry inside single nuclear pore complexes in vivo.

The nuclear pore complex (NPC) is one of the largest supramolecular structures in eukaryotic cells. Its octagonal ring-scaffold perforates the nuclear envelope and features a unique molecular machinery that regulates nucleocytoplasmic transport. NPCs are composed of ~30 different nucleoporins (Nups), averaged at 8, 16 or 32 copies per NPC.

Nuclear pore complex protein sequences determine overall copolymer brush structure and function.

The transport of cargo across the nuclear membrane is highly selective and accomplished by a poorly understood mechanism involving hundreds of nucleoporins lining the inside of the nuclear pore complex (NPC). Currently, there is no clear picture of the overall structure formed by this collection of proteins within the pore, primarily due to their disordered nature. We perform coarse-grained simulations of both individual nucleoporins and grafted rings of nups mimicking the in vivo geometry of the NPC and supplement this with polymer brush modeling.

Physical motif clustering within intrinsically disordered nucleoporin sequences reveals universal functional features.

Bioinformatics of disordered proteins is especially challenging given high mutation rates for homologous proteins and that functionality may not be strongly related to sequence. Here we have performed a novel bioinformatic analysis, based on the spatial clustering of physically relevant features such as binding motifs and charges within disordered proteins, on thousands of Nuclear Pore Complex (NPC) FG motif containing proteins (FG nups). The biophysical mechanism by which FG nups regulate nucleocytoplasmic transport has remained elusive.

Single-molecule analysis of the recognition forces underlying nucleo-cytoplasmic transport.

To move molecules across the nuclear envelope they have to overcome the selective barrier of the nuclear pore which is formed by nucleoporins with FG repeats. For this, they are chaperoned by shuttling receptors that interact with FG nups thereby passing the barrier with an unresolved mechanism. We explored the molecular binding and dissociation of this process using single molecule force spectroscopy showing that no energetic cost is required for translocation.