Background Crepitus of the knee may mirror structural and functional changes in the joint during motion. Although the magnitude of these sounds increases with greater cartilage damage, it is unclear whether knee joint sounds also reflect joint loading. Methods Twelve healthy volunteers (mean 26 (SD 3.6) years, 7 females) participated in the randomized-balanced crossover study. Knee joint sounds were

Chromosomes are positioned non-randomly inside the nucleus to coordinate with their transcriptional activity. The molecular mechanisms that dictate the global genome organization and the nuclear localization of individual chromosomes are not fully understood. We introduce a polymer model to study the organization of the diploid human genome: it is data-driven as all parameters can be derived from Hi-C

Background The introduction of targeted therapies for the treatment of BRAF-mutant melanomas have improved survival rates in a significant proportion of patients. Nonetheless, the emergence of resistance to treatment remains inevitable in most patients. Scope of review Here, we review known and emerging molecular mechanisms that underlay the development of resistance to MAPK inhibition in melanoma

Background The investigation of the interactions between cells and active materials is pivotal in the emerging 3D printing-biomaterial application fields. Here, lipidomics has been used to explore the early impact of alginate (ALG) hydrogel architecture (2D films or 3D printed scaffolds) and the type of gelling agent (CaCl2 or FeCl3) on the lipid profile of human fibroblasts. Methods 2D and 3D ALG

Non-small cell lung cancer (NSCLC) accompanied by diabetes is an important risk factor affecting the prognosis of patients with NSCLC in clinical practice. However, the effect of high glucose (HG) in the pathogenesis of NSCLC remains elusive. It has been found that the RNA-binding protein Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) plays important roles in various diseases, including

Here we report the effects of ammonium on the main biophysical features of neurons and astrocytes during the first minutes of exposure. We found that ammonium causes the depolarization of neurons, which leads to the generation of high-frequency action potentials (APs). The initial alkalization and subsequent acidification of the intracellular medium in neurons occur along with the generation of calcium

Autoimmune Thyroid diseases, such as Hashimoto's thyroiditis, is characterized by lymphocytic infiltration and altered function of the thyroid. During inflammation, it has been reported a decreased expression in Tg and NIS, accompanied by an increase in HA production that accumulates in the gland. HA fragments produced in different pathological states can modulate gene expression in a variety of cell

Hypoplastic left heart syndrome (HLHS) represents approximately 9% of all congenital heart defects and is one of the most complex, with the left side of the heart being generally underdeveloped. Numerous studies demonstrate that intracardiac fluid flow patterns in the embryonic and fetal circulation can impact cardiac structural formation and remodeling. This highlights the importance of quantifying

Shear elastic modulus (G) can differ among individuals due to muscle size and other factors, even for constant muscle force. Inter-individual comparisons of G usually require normalization by maximal voluntary contraction (MVC), but MVC procedures may not be appropriate for certain clinical populations including those presenting with pain or other compromised functionality. This study aimed to test

In vitro experiments confirmed that antibacterial photodynamic treatment (aPDT) inactivates periodontal pathogens. However, more effective sterilization is needed in the complex oral environment. This study tested whether dihydroartemisinin (DHA) enhanced the photokilling effect of aPDT on Porphyromonas gingivalis(P. gingivalis) in planktonic and biofilm states. aPDT combining toluidine blue O (TBO)

Photoageing and skin cancer are major causes of morbidity and are a high cost to society. Interest in the development of photoprotective agents for inclusion in topical cosmetic and sunscreen products is profound. Recently, amino acids with a sulfinic group, notably hypotaurine, have been included as ingredients in cosmetic preparations. However, the mechanism of action of hypotaurine as a possible

Self-organisation of Min proteins is responsible for the spatial control of cell division in Escherichia coli, and has been studied both in vivo and in vitro. Intriguingly, the protein patterns observed in these settings differ qualitatively and quantitatively. This puzzling dichotomy has not been resolved to date. Using reconstituted proteins in laterally wide microchambers with a well-controlled

Fluorescence microscopy has been one of the most discovery-rich methods in biology. In the digital age, the discipline is becoming increasingly quantitative. Virtually all biological laboratories have access to fluorescence microscopes, but abilities to quantify biomolecule copy numbers are limited by the complexity and sophistication associated with current quantification methods. Here, we present

In the cell, DNA is arranged into highly-organised and topologically-constrained (supercoiled) structures. It remains unclear how this supercoiling affects the detailed double-helical structure of DNA, largely because of limitations in spatial resolution of the available biophysical tools. Here, we overcome these limitations, by a combination of atomic force microscopy (AFM) and atomistic molecular

Hyperpolarization-activated and cyclic nucleotide (HCN) modulated channels are tetrameric cation channels. In each of the four subunits, the intracellular cyclic nucleotide-binding domain (CNBD) is coupled to the transmembrane domain via a helical structure, the C-linker. High-resolution channel structures suggest that the C-linker enables functionally relevant interactions with the opposite subunit

Less than a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 22 million people worldwide with a death toll approaching 1 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies.

Linker histones bind to nucleosomes and modify chromatin structure and dynamics as a means of epigenetic regulation. Biophysical studies have shown that chromatin fibers can adopt a plethora of conformations with varying levels of compaction. Linker histone condensation, and its specific binding disposition, has been associated with directly tuning this ensemble of states. However, the atomistic dynamics

Here we show an interplay between the structures present in ionization tracks and nucleocapsid RNA structural biology, using fast ion beam inactivation of the severe acute respiratory syndrome coronavirus (SARS-CoV) virion as an example. This interplay is one of the key factors in predicting dose-inactivation curves for high energy ion beam inactivation of virions. We also investigate the adaptation

Epidemiological models usually contain a set of parameters that must be adjusted based on available observations. Once a model has been calibrated, it can be used as a forecasting tool to make predictions and to evaluate contingency plans. It is customary to employ only point estimators of model parameters for such predictions. However, some models may fit the same data reasonably well for a broad

In the absence of other tools, monitoring the effects of protective measures, including social distancing and forecasting the outcome of outbreaks is of immense interest. Real-time data is noisy and very often hampered by systematic errors in reporting. Detailed epidemic models may contain a large number of empirical parameters, which cannot be determined with sufficient accuracy. In this paper, we

The aim of this paper is to investigate the effects of a rotating ion beam on the temperature gradient instability (TGI) in completely ionized plasmas. The interplay of the temperature and density gradients provide the basis for experiencing an unstable inhomogeneous plasma medium due to TGI taken under consideration. The density and temperature gradients are considered perpendicular to the magnetic

We revisit the problem of the reduction of the three-dimensional (3D) dynamics of Bose-Einstein condensates, under the action of strong confinement in one direction (z), to a 2D mean-field equation. We address this problem for the confining potential with a singular term, viz ., Vz(z)=2z2+ζ2/z2, with constant $$. A quantum phase transition is induced by the latter term, between the ground state (GS)

We continue our theoretical study of a recently proposed two-dimensional colloidal system with attractive critical Casimir and repulsive magnetic dipole forces that can be tuned easily and independently from each other via the temperature and the strength of an external magnetic field, respectively [K. Marolt, M. Zimmermann and R. Roth, ]. Using this freedom, it is possible to construct a competing

The Sitnikov problem is a classical problem broadly studied in physics which can represent an illustrative example of chaotic scattering. The relativistic version of this problem can be attacked by using the post-Newtonian formalism. Previous work focused on the role of the gravitational radius λ on the phase space portrait. Here, we add two new and relevant issues on the influence of the gravitational

This paper studies the effect of stress inhomogeneity on the behaviour of fluid-driven fracture development in weakly consolidated granular systems. Using numerical models we investigate the change in fracture growth rate and fracture pattern structure in unconsolidated granular packs (also refered to as soft-sands) as a function of the change in the confining stresses applied to the system. Soft-sands

A spin system can be thought of as an information coding system that transfers information of the interaction configuration into information of the equilibrium state of the spin variables. Hence it can be expected that the relations between the interaction configuration and equilibrium states are consistent with the known laws of information theory. We show that Shannon’s rate-distortion theorem can

We recently argued that a self-propelled particle is formally equivalent to a system consisting of two subsystems coupled by a non-reciprocal interaction [Phys. Rev. E 100, 050603(R) (2019)]. Here we show that this non-reciprocal coupling allows to extract useful work from a single self-propelled particle maintained at constant temperature, by using an aligning interaction to control correlations between

A planar laser pulse propagating in vacuum can exhibit an extremely large ponderomotive force. This force, however, cannot impart net energy to an electron: As the pulse overtakes the electron, the initial impulse from its rising edge is completely undone by an equal and opposite impulse from its trailing edge. Here we show that planar-like "flying focus’’ pulses can break this symmetry, imparting

Spectral statistics of hermitian random Toeplitz matrices with independent identically distributed elements is investigated numerically. It is found that eigenvalue statistics of complex Toeplitz matrices is surprisingly well approximated by the semi-Poisson distribution belonging to intermediate-type statistics observed in certain pseudo-integrable billiards. The origin of intermediate behaviour could

We calculate the ground state energy density ϵ(g) for the one dimensional N-state quantum clock model up to order 18, where g is the coupling and N=3,4,5,...,10,20. Using methods based on Pad'e approximation, we extract the singular structure of ϵ″(g) or ϵ(g). They correspond to the specific heat and free energy of the classical 2D clock model. We find that, for N=3,4, there is a single critical point

Many systems with propagation dynamics, such as spike propagation in neural networks and spreading of infectious diseases, can be approximated by autoregressive models. The estimation of model parameters can be complicated by the experimental limitation that one observes only a fraction of the system (subsampling) and potentially time-dependent parameters, leading to incorrect estimates. We show analytically

Complex plasmas are interesting systems as the charged dust can self-assemble into different types of ordered structures. To understand the mechanisms which govern the transitions from one type of structure to another, it is necessary to know both the dust charge and the confining electric fields within the environment, parameters which are difficult to measure independently. The problem is further

Intercellular adhesion of keratinocytes depends critically on desmosomes which, during maturation, acquire a hyper-adhesive and thus Ca2+-independent state. Here, we investigated the roles of desmoglein (Dsg) 3 and plakophilins (Pkps) in hyper-adhesion. Atomic force microscopy (AFM) single molecule force mappings revealed increased Dsg3 molecules but not Dsg1 molecules binding strength in murine keratinocytes

In situ structures of the spirochete flagellar motor by cryo-ET reveal two distinct modes of interactions between the rotor ring and stator units. Together with new cryo-EM structures of the isolated stator units, this work provides insights into the mechanisms of torque generation and directional switch.

Viruses use internal ribosome entry sites (IRES) to hijack host ribosomes and promote cap-independent translation. Although they are well-studied in bulk, the dynamics of IRES-mediated translation remain unexplored at the single-molecule level. Here, we developed a bicistronic biosensor encoding distinct repeat epitopes in two open reading frames (ORFs), one translated from the 5′ cap, and the other

Transcription activation by distal enhancers is essential for cell-fate specification and maintenance of cellular identities. How long-range gene regulation is physically achieved, especially within complex regulatory landscapes of non-binary enhancer–promoter configurations, remains elusive. Recent nanoscopy advances have quantitatively linked promoter kinetics and ~100- to 200-nm-sized clusters of

The Ca-ATPase isoform 2a (SERCA2a) re-sequesters cytosolic Ca2+ into the sarcoplasmic reticulum (SR) of cardiac myocytes, enabling muscle relaxation during diastole. A central factor in heart failure is abnormally high cytosolic [Ca2+], resulting in pathophysiology and decreased cardiac performance. Therefore, augmentation of the SERCA2a Ca2+ transport activity is a promising therapeutic approach.

G protein-coupled receptors (GPCRs) are the largest class of transmembrane proteins, making them an important target for therapeutics. Activation of these receptors is modulated by orthosteric ligands, which stabilize one or several states within a complex conformational ensemble. The intra- and inter-state dynamics, however, is not well documented. Here, we used single-molecule fluorescence to measure

Cytoplasmic dynein is the primary motor for microtubule minus-end-directed transport and is indispensable to eukaryotic cells. Although each motor domain of dynein contains three active AAA+ ATPases (AAA1, 3, and 4), only the functions of AAA1 and 3 are known. Here, we use single-molecule fluorescence and optical tweezers studies to elucidate the role of AAA4 in dynein's mechanochemical cycle. We demonstrate

Biological membranes have been prominent targets for coarse-grained (CG) molecular dynamics (MD) simulations. While minimal CG lipid models with three-beads per lipid and quantitative CG lipid models with >10-beads per lipid have been well studied, in between them, CG lipid models with a compatible resolution to residue-level CG protein models are much less developed. Here, we extended a previously

Filopodia are actin-rich structures, present on the surface of practically every known eukaryotic cell. These structures play a pivotal role in specific cell-cell and cell-matrix interactions by allowing cells to explore their environment, generate mechanical forces, perform chemical signaling, or convey signals via intercellular tunneling nano-bridges. The dynamics of filopodia appear quite complex

Structured RNA elements are essential for biology and are ubiquitously used by viruses to control diverse infection-critical processes. Single-stranded RNA viruses often encode multiple processes into a single RNA element to maximize the functional capacity of their compact genomes. These important and elegant 'multifunctional' RNAs are hypothesized to use programmed structural changes to coordinate

Capillary forces are driven by interactions between liquids and surfaces. These forces are crucial for many processes ranging from biology and physics to engineering, such as the motion of aquatic insects on the surface of water, modulation of the material properties of spider silk, and self-assembly of small objects and microstructures. Recent studies have shown that cells assemble biomolecular condensates

Structure determination methods are needed to resolve the atomic details that underlie protein function. X-ray crystallography has provided most of our knowledge of protein structure but is constrained by the need for large, well-ordered crystals and the loss of phase information. The rapidly developing methods of serial femtosecond crystallography, micro-electron diffraction, and single-particle reconstruction

Parvalbumin (PV) is a calcium binding protein expressed in humans, fish and avian species. In these organisms, the calcium (Ca2+) affinities of specific PV isoforms can vary by orders of magnitude. Despite the availability of high resolution structural data for many PV isoforms, the structural bases for how such proteins confer widely-varying divalent Ca2+ affinities and selectivities against common

A near-atomic resolution structure of the mouse voltage dependent anion channel (mVDAC) is determined by combining cryogenic focused ion-beam (FIB) milling and microcrystal electron diffraction (MicroED). The crystals were grown in a viscous modified bicelle suspension which limited their size and made them unsuitable for conventional X-ray crystallography. Individual thin, plate-like crystals were

Scientific research, with its myriad disciplines, global reach, and massive economic impact, moves society forward by illuminating new understandings of our planet, its organisms, and the human condition. While the scientific community and life science industry advance knowledge, this comes at a large environmental cost. Scientists across the globe are recognizing the need to be more efficient in their