Underrepresentation of women in cardiovascular disease clinical Trials-What's in a Name?

Background: Cardiovascular disease is the leading cause of death in women worldwide. Yet, women are often underrepresented in cardiovascular clinical trials. Trial characteristics may influence the participation of women.

Uniting education, research, healthcare, and society to advance women's heart health.

Complex health challenges require professionals to operate across disciplines and to better connect with society. Here, we showcase a community-engaged and challenge-based educational model in which undergraduate students conduct transdisciplinary research on authentic complex biomedical problems. This concept reinforces translational medicine, human capital, and exemplifies synergy between education, research, healthcare, and society.

Effect of Particle Heterogeneity in Catalytic Copper-Containing Single-Chain Polymeric Nanoparticles Revealed by Single-Particle Kinetics.

Single-chain polymeric nanoparticles (SCPNs) have been extensively explored as a synthetic alternative to enzymes for catalytic applications. However, the inherent structural heterogeneity of SCPNs, arising from the dispersity of the polymer backbone and stochastic incorporation of different monomers as well as catalytic moieties, is expected to lead to variations in catalytic activity between individual particles. To understand the effect of structural heterogeneities on the catalytic performance of SCPNs, techniques are required that permit researchers to directly monitor SCPN activity at the single-polymer level.

Bisurea-Based Supramolecular Polymers for Tunable Biomaterials.

Water-soluble supramolecular polymers show great potential to develop dynamic biomaterials with tailored properties. Here, we elucidate the morphology, stability and dynamicity of supramolecular polymers derived from bisurea-based monomers. An accessible synthetic approach from 2,4-toluene diisocyanate (TDI) as the starting material is developed.

Bootstrapping Elliptic Feynman Integrals Using Schubert Analysis.

The symbol bootstrap has proven to be a powerful tool for calculating polylogarithmic Feynman integrals and scattering amplitudes. In this Letter, we initiate the symbol bootstrap for elliptic Feynman integrals. Concretely, we bootstrap the symbol of the twelve-point two-loop double-box integral in four dimensions, which depends on nine dual-conformal cross ratios.

Does preappointment gabapentin affect neurological examination findings? A prospective, randomized and blinded study in healthy cats.

Objectives: The aim of this study was to evaluate the influence of a preappointment oral dose of gabapentin on the neurological examination of cats.

Methods: A prospective, randomized and blinded clinical trial was conducted in 35 client-owned healthy cats. Cats were scheduled for two appointments and randomly assigned to receive either a placebo or a 100 mg gabapentin capsule prior to the second veterinary visit.

Evaluation of the effects of gabapentin on the physiologic and echocardiographic variables of healthy cats: a prospective, randomized and blinded study.

Objectives: The aim of this study was to evaluate, using echocardiography, the effects of oral administration of a single dose of gabapentin on the physiologic variables (heart rate [HR], respiratory rate [RR] and systolic blood pressure [SBP]) and systolic and diastolic cardiac function of healthy cats.

Methods: This was a prospective, randomized and blinded study with 40 healthy cats aged between 6 months and 2 years. The cats' health status was assessed on the first appointment (T1) when they underwent a physical examination, complete blood count, biochemical profile, assessment of physiologic variables and echocardiogram.

How Subtle Changes Can Make a Difference: Reproducibility in Complex Supramolecular Systems.

The desire to construct complex molecular systems is driven by the need for technological (r)evolution and our intrinsic curiosity to comprehend the origin of life. Supramolecular chemists tackle this challenge by combining covalent and noncovalent reactions leading to multicomponent systems with emerging complexity. However, this synthetic strategy often coincides with difficult preparation protocols and a narrow window of suitable conditions.

Structure and Dynamics of Supramolecular Polymers: Wait and See.

The introduction of stereogenic centers in supramolecular building blocks is used to unveil subtle changes in supramolecular structure and dynamics over time. Three stereogenic centers based on deuterium atoms were introduced in the side chains of a benzene-1,3,5-tricarboxamide (BTA) resulting in a supramolecular polymer in water that at first glance has a structure and dynamics identical to its achiral counterpart. Using three different techniques, the properties of the double helical polymers are compared after 1 day and 4 weeks.

Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19.

A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.

Quantifying Guest-Host Dynamics in Supramolecular Assemblies to Analyze Their Robustness.

The most basic function of synthetic microenvironments for tissue engineering is to act as a physical substrate for cell attachment, migration, and proliferation, similar to the natural cell environment. Functionalization of supramolecular materials with guest compounds that display the same recognition moieties is a common strategy to introduce biofunctionality. However, besides a robust interaction with the material, a certain level of dynamics needs to be conserved for an adaptive interface toward the living environment.

Kinetic Analysis as a Tool to Distinguish Pathway Complexity in Molecular Assembly: An Unexpected Outcome of Structures in Competition.

While the sensitive dependence of the functional characteristics of self-assembled nanofibers on the molecular structure of their building blocks is well-known, the crucial influence of the dynamics of the assembly process is often overlooked. For natural protein-based fibrils, various aggregation mechanisms have been demonstrated, from simple primary nucleation to secondary nucleation and off-pathway aggregation. Similar pathway complexity has recently been described in synthetic supramolecular polymers and has been shown to be intimately linked to their morphology.

Controlled translocation of DNA through nanopores in carbon nano-, silicon-nitride- and lipid-coated membranes.

We investigated experimentally and theoretically the translocation forces when a charged polymer is threaded through a solid-state nanopore and found distinct dependencies on the nanopore diameter as well as on the nano membrane material chemistry. For this purpose we utilized dedicated optical tweezers force mechanics capable of probing the insertion of negatively charged double-stranded DNA inside a helium-ion drilled nanopore. We found that both the diameter of the nanopore and the membrane material itself have significant influences on the electroosmotic flow through the nanopore and thus on the threading force.

Rational design of a cytotoxic dinuclear Cu2 complex that binds by molecular recognition at two neighboring phosphates of the DNA backbone.

The mechanism of the cytotoxic function of cisplatin and related anticancer drugs is based on their binding to the nucleobases of DNA. The development of new classes of anticancer drugs requires establishing other binding modes. Therefore, we performed a rational design for complexes that target two neighboring phosphates of the DNA backbone by molecular recognition resulting in a family of dinuclear complexes based on 2,7-disubstituted 1,8-naphthalenediol.

Hydrodynamic slip on DNA observed by optical tweezers-controlled translocation experiments with solid-state and lipid-coated nanopores.

We use optical tweezers to investigate the threading force on a single dsDNA molecule inside silicon-nitride nanopores between 6 and 70 nm in diameter, as well as lipid-coated solid-state nanopores. We observe a strong increase of the threading force for decreasing nanopore size that can be attributed to a significant reduction in the electroosmotic flow (EOF), which opposes the electrophoresis. Additionally, we show that the EOF can also be reduced by coating the nanopore wall with an electrically neutral lipid bilayer, resulting in an 85% increase in threading force.

A modular approach to easily processable supramolecular bilayered scaffolds with tailorable properties.

Engineering of anisotropic tissues demands extracellular matrix (ECM) mimicking scaffolds with an asymmetric distribution of functionalities. We here describe a convenient, modular approach based on supramolecular building blocks to form electrospun bilayered scaffolds with tailorable properties. Polymers and peptides functionalized with hydrogen-bonding ureido-pyrimidinone (UPy) moieties can easily be mixed-and-matched to explore new material combinations with optimal properties.

Video-based and interference-free axial force detection and analysis for optical tweezers.

For measuring the minute forces exerted on single molecules during controlled translocation through nanopores with sub-piconewton precision, we have developed a video-based axial force detection and analysis system for optical tweezers. Since our detection system is equipped with a standard and versatile CCD video camera with a limited bandwidth offering operation at moderate light illumination with minimal sample heating, we integrated Allan variance analysis for trap stiffness calibration. Upon manipulating a microbead in the vicinity of a weakly reflecting surface with simultaneous axial force detection, interference effects have to be considered and minimized.

Mechanically induced chemiluminescence from polymers incorporating a 1,2-dioxetane unit in the main chain.

Nature uses mechanochemical transduction processes to achieve diverse and vital functions, such as hearing, cellular adhesion and gating of ion channels. One fascinating example of biological mechanotransduction is the emission of light on mechanical stimulation. However, molecular-level transduction of force into luminescence in a synthetic system remains a challenge.

Nanopore translocation dynamics of a single DNA-bound protein.

We study the translocation dynamics of a single protein molecule attached to a double-stranded DNA that is threaded through a solid-state nanopore by optical tweezers and an electric field (nanopore force spectroscopy). We find distinct asymmetric and retarded force signals that depend on the protein charge, the DNA elasticity and its counterionic screening in the buffer. A theoretical model where an isolated charge on an elastic, polyelectrolyte strand is experiencing an anharmonic nanopore potential was developed.

Dynamic translocation of ligand-complexed DNA through solid-state nanopores with optical tweezers.

We investigated the threading and controlled translocation of individual lambda-DNA (λ-DNA) molecules through solid-state nanopores with piconewton force sensitivity, millisecond time resolution and picoampere ionic current sensitivity with a set-up combining quantitative 3D optical tweezers (OT) with electrophysiology. With our virtually interference-free OT set-up the binding of RecA and single peroxiredoxin protein molecules to λ-DNA was quantitatively investigated during dynamic translocation experiments where effective forces and respective ionic currents of the threaded DNA molecule through the nanopore were measured during inward and outward sliding. Membrane voltage-dependent experiments of reversible single protein/DNA translocation scans yield hysteresis-free, asymmetric single-molecule fingerprints in the measured force and conductance signals that can be attributed to the interplay of optical trap and electrostatic nanopore potentials.

Binding kinetics of bisintercalator Triostin a with optical tweezers force mechanics.

The binding kinetics of the intercalative binding of Triostin A to lambda-DNA was investigated by measuring the force extension response of the DNA-ligand complexes with an optical tweezers system. These force response curves, containing the information about different binding properties, were analyzed based on a recent method (put forth by another research group) for monointercalators that was extended to bisintercalators. Our binding analysis reveals an exponential dependence of the association constant on the applied external force as well as a decreasing binding site size.

Dehydrogenation of tertiary amines in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

In the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) analysis of various compounds synthesized in our laboratory, strong [M - H]+ ion peaks were often observed for the molecules with tertiary amino groups. In this work, the MALDI TOF MS behavior of two groups of compounds that incorporate tertiary amino moieties was investigated. One group is bisurea dimethylanilines (BUDMAs) prepared for the study of molecular recognition in thermoplastic elastomers, and the other group is the poly(propylene imine) diaminobutane dendrimers.

Molecular recognition in poly(epsilon-caprolactone)-based thermoplastic elastomers.

The molecular recognition properties of the hydrogen bonding segments in biodegradable thermoplastic elastomers were explored, aiming at the further functionalization of these potentially interesting biomaterials. A poly(epsilon-caprolactone)-based poly(urea) 2 was synthesized and characterized in terms of mechanical properties, processibility and histocompatibility. Comparison of the data with those obtained from the structurally related poly(urethane urea) 1 revealed that the difference in hard segment structure does not significantly affect the potency for application as a biomaterial.

Chemical and biological properties of supramolecular polymer systems based on oligocaprolactones.

We show that materials with a diverse range of mechanical and biological properties can be obtained using a modular approach by simply mixing different ratios of oligocaprolactones that are either end-functionalized or chain-extended with quadruple hydrogen bonding ureido-pyrimidinone (UPy) moieties. The use of two UPy-synthons allows for easy synthesis of UPy-modified polymers resulting in high yields. Comparison of end-functionalized UPy-polymers with chain-extended UPy-polymers shows that these polymers behave distinctively different regarding their material and biological properties.

Correlation between complementation group for immortality and DNA synthesis inhibitors.

Previous studies had demonstrated that a DNA synthesis inhibitor(s) was produced by senescent but not young human diploid fibroblasts (HDF). Analysis of immortal human cell lines led to the finding that SUSM-1, carcinogen-treated immortal human liver fibroblast cells, expressed a potent inhibitor of DNA synthesis that was active in proliferation-competent young HDF but did not affect the SUSM-1 cell line itself. To determine whether one mechanism of escape from senescence to the immortal phenotype involved the loss of response to such DNA synthesis inhibitors, we initiated the present study analyzing a larger number of immortal human cell lines representative of the four complementation groups for indefinite division identified to date.