Toward a comprehensive profiling of alternative splicing proteoform structures, interactions and functions.

The mRNA splicing machinery has been estimated to generate 100,000 known protein-coding transcripts for 20,000 human genes (Ensembl, Sept. 2024). However, this set is expanding with the massive and rapidly growing data coming from high-throughput technologies, particularly single-cell and long-read sequencing.

Stability of [10-12]cycloparaphenylene complexes with pristine fullerenes C and endohedral metallofullerenes MN@C.

[]Cycloparaphenylenes ([]CPPs) are strained macrocycles, comprising only sp-hybridized carbon atoms. In recent years, []CPPs have become of great research interest in the field of supramolecular chemistry since their special structure enables the formation of novel host-guest complexes. In this work, we investigate the gas-phase chemistry of noncovalent complexes of [10-12]CPP with the pristine fullerenes C and the endohedral metallofullerenes (EMFs) ScN@-C, ScN@-C and MN@-C (M = Sc, Y, Lu, Gd).

Nanohoops Favour Light-Induced Energy Transfer over Charge Separation in Porphyrin/[10]CPP/Fullerene Rotaxanes.

[2]Rotaxanes offer unique opportunities for studying and modulating charge separation and energy transfer, because the mechanical bond allows the robust, yet spatially dynamic tethering of photoactive groups. In this work, we synthesized [2]rotaxane triads comprising a central (aza)[10]CPP⊃C bis-adduct complex and two zinc porphyrin stoppers to address how the movable nanohoop affects light-induced charge separation and energy transfer between the rotaxane subcomponents. We found that neither the parent nanohoop [10]CPP nor its electron-deficient analogue aza[10]CPP actively participate in charge separation.

Predicting the Dynamic Interaction of Intrinsically Disordered Proteins.

Intrinsically disordered proteins (IDPs) participate in various biological processes. Interactions involving IDPs are usually dynamic and are affected by their inherent conformation fluctuations. Comprehensive characterization of these interactions based on current techniques is challenging.

Conformational Landscapes and Energetics of Carbon Nanohoops and their Ring-in-Ring Complexes.

Carbon nanohoops are promising precursors for the synthesis of nanotubes, whose structural dynamics are not well understood. Here, we investigate the conformational landscape and energetics of cycloparaphenylenes (CPPs), a methylene-bridged CPP and a carbon nanobelt. These nanohoops can form host-guest complexes with other rings, and understanding their structure is crucial for predicting their properties and identifying potential applications.

Frustraevo: a web server to localize and quantify the conservation of local energetic frustration in protein families.

According to the Principle of Minimal Frustration, folded proteins can only have a minimal number of strong energetic conflicts in their native states. However, not all interactions are energetically optimized for folding but some remain in energetic conflict, i.e.

Local energetic frustration conservation in protein families and superfamilies.

Energetic local frustration offers a biophysical perspective to interpret the effects of sequence variability on protein families. Here we present a methodology to analyze local frustration patterns within protein families and superfamilies that allows us to uncover constraints related to stability and function, and identify differential frustration patterns in families with a common ancestry. We analyze these signals in very well studied protein families such as PDZ, SH3, ɑ and β globins and RAS families.

New Insights into Ring-In-Ring Complexes of []Cycloparaphenylenes including the [12]Carbon Nanobelt.

The supramolecular chemistry of cycloparaphenylenes (CPPs) is characterized by the ability of the ring system to undergo both concave and convex π-π interactions. As a consequence, ring-in-ring complexes can be formed in which the CPP serves as the host as well as the guest molecule ([ + ]CPP⊃[]CPP). In this work, host-guest ring-in-ring complexes of []CPPs ( = 5-12) are investigated by means of electrospray ionization-tandem mass spectrometry (ESI-MS) and laser desorption ionization mass spectrometry (LDI-MS).

A molecular Popeye: Li@C and its complexes with []cycloparaphenylenes.

In this work, we compare for the first time the stability of []cycloparaphenylene ([]CPP)-based host-guest complexes with Li@C and C in the gas and the solution phase. Our gas-phase experiments reveal a significant increase in stability for the complexes featuring [9-12]CPP with Li@C. This increased interaction strength is also observed in solution.

Tunable Macrocyclic Polyparaphenylene Nanolassos via Copper-Free Click Chemistry.

Deriving diverse compound libraries from a single substrate in high yields remains to be a challenge in cycloparaphenylene chemistry. In here, a strategy for the late-stage functionalization of shape-persistent alkyne-containing cycloparaphenylene has been explored using readily available azides. The copper-free [3+2]azide-alkyne cycloaddition provided high yields (>90 %) in a single reaction step.

Two Rings Around One Ball: Stability and Charge Localization of [1 : 1] and [2 : 1] Complex Ions of [10]CPP and C *.

We investigate the gas-phase chemistry of noncovalent complexes of [10]cycloparaphenylene ([10]CPP) with C and C by means of atmospheric pressure photoionization and electrospray ionization mass spectrometry. The literature-known [1 : 1] complexes, namely [10]CPP⊃C and [10]CPP⊃C , are observed as radical cations and anions. Their stability and charge distribution are studied using energy-resolved collision-induced dissociation (ER-CID).

Should the COVID-19 lockdown be relaxed or intensified in case a vaccine becomes available?

Immediately after the start of the COVID-19 pandemic in Early 2020, most affected countries reacted with strict lockdown to limit the spread of the virus. Since that time, the measures were adapted on a short time basis according to certain numbers (i.e.

Chasing up and locking down the virus: Optimal pandemic interventions within a network.

During the COVID-19 pandemic countries invested significant amounts of resources into its containment. In early stages of the pandemic most of the (nonpharmaceutical) interventions can be classified into two groups: (i) testing and identification of infected individuals, (ii) social distancing measures to reduce the transmission probabilities. Furthermore, both groups of measures may, in principle, be targeted at certain subgroups of a networked population.

FrustratometeR: an R-package to compute local frustration in protein structures, point mutants and MD simulations.

Summary: Once folded, natural protein molecules have few energetic conflicts within their polypeptide chains. Many protein structures do however contain regions where energetic conflicts remain after folding, i.e.

Frustration in Fuzzy Protein Complexes Leads to Interaction Versatility.

Disordered proteins frequently serve as interaction hubs involving a constrained variety of partners. Complexes with different partners frequently exhibit distinct binding modes, involving regions that remain disordered in the bound state. While the conformational properties of disordered proteins are well-characterized in their free states, less is known about the molecular mechanisms by which specificity can be achieved not with one but with multiple partners.

Fuzziness and Frustration in the Energy Landscape of Protein Folding, Function, and Assembly.

Are all protein interactions fully optimized? Do suboptimal interactions compromise specificity? What is the functional impact of frustration? Why does evolution not optimize some contacts? Proteins and their complexes are best described as ensembles of states populating an energy landscape. These ensembles vary in breadth from narrow ensembles clustered around a single average X-ray structure to broader ensembles encompassing a few different functional "taxonomic" states on to near continua of rapidly interconverting conformations, which are called "fuzzy" or even "intrinsically disordered". Here we aim to provide a comprehensive framework for confronting the structural and dynamical continuum of protein assemblies by combining the concepts of energetic frustration and interaction fuzziness.

An analysis of Ibuprofen enantiomers in high concentrations of sodium chloride with SARS-CoV-2 main protease.

2020 will be remembered worldwide for the outbreak of Coronavirus disease (COVID-19), which quickly spread until it was declared as a global pandemic. The main protease (Mpro) of SARS-CoV-2, a key enzyme in coronavirus, represents an attractive pharmacological target for inhibition of SARS-CoV-2 replication. Here, we evaluated whether the anti-inflammatory drug Ibuprofen, may act as a potential SARS-CoV-2 Mpro inhibitor, using an study.

A training algorithm for networks of high-variability reservoirs.

Physical reservoir computing approaches have gained increased attention in recent years due to their potential for low-energy high-performance computing. Despite recent successes, there are bounds to what one can achieve simply by making physical reservoirs larger. Therefore, we argue that a switch from single-reservoir computing to multi-reservoir and even deep physical reservoir computing is desirable.

Large Ankyrin repeat proteins are formed with similar and energetically favorable units.

Ankyrin containing proteins are one of the most abundant repeat protein families present in all extant organisms. They are made with tandem copies of similar amino acid stretches that fold into elongated architectures. Here, we built and curated a dataset of 200 thousand proteins that contain 1.

Local frustration around enzyme active sites.

Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations of this principle open up the possibility to encode the complex energy landscapes that are required for active biological functions. We survey the local energetic frustration patterns of all protein enzymes with known structures and experimentally annotated catalytic residues.

Training Passive Photonic Reservoirs With Integrated Optical Readout.

As Moore's law comes to an end, neuromorphic approaches to computing are on the rise. One of these, passive photonic reservoir computing, is a strong candidate for computing at high bitrates (>10 Gb/s) and with low energy consumption. Currently though, both benefits are limited by the necessity to perform training and readout operations in the electrical domain.

Quantifying Economic Dependency.

In this paper we compare several types of economic dependency ratios for a selection of European countries. These dependency ratios take into account not only the demographic structure of the population, but also the differences in age-specific economic behaviour such as labour market activity, income and consumption as well as age-specific public transfers. In selected simulations where we combine patterns of age-specific economic behaviour and transfers with population projections, we show that in all countries population ageing would lead to a pronounced increase in dependency ratios if present age-specific patterns were not to change.

A deterministic approach to the adapted optode placement for illumination of highly scattering tissue.

A novel approach is presented for computing optode placements that are adapted to specific geometries and tissue characteristics, e.g., in optical tomography and photodynamic cancer therapy.

High-performance image reconstruction in fluorescence tomography on desktop computers and graphics hardware.

Image reconstruction in fluorescence optical tomography is a three-dimensional nonlinear ill-posed problem governed by a system of partial differential equations. In this paper we demonstrate that a combination of state of the art numerical algorithms and a careful hardware optimized implementation allows to solve this large-scale inverse problem in a few seconds on standard desktop PCs with modern graphics hardware. In particular, we present methods to solve not only the forward but also the non-linear inverse problem by massively parallel programming on graphics processors.