Background The pathophysiology of cerebral aneurysm is complex and poorly understood, and it can have the most catastrophic clinical presentation. Flow dynamics is a key player in the initiation and progression of aneurysm. Better understanding the interaction between hemodynamic loading and biomechanical wall responses can help to add the missing piece on aneurysmal pathophysiology. In this laboratory

Trk-A is a receptor tyrosine kinase (RTK) which plays an essential role in the development and functioning of the nervous system. Trk-A is expressed in neurons and signals in response to two ligands, NGF and NT-3, with very different functional consequences. Thus, NGF and NT-3 are "biased" ligands for Trk-A. Since it has been hypothesized that biased RTK ligands induce differential stabilization of

Sudden cardiac arrest is a malfunction of the heart’s electrical system, typically caused by ventricular arrhythmias, that can lead to sudden cardiac death (SCD) within minutes. Epidemiological studies have shown that SCD and ventricular arrhythmias are more likely to occur in the morning than in the evening, and laboratory studies indicate that these daily rhythms in adverse cardiovascular events

Many immunoreceptors have cytoplasmic domains that are intrinsically disordered (i.e., have high configurational entropy), have multiple sites of post-translational modification (e.g., tyrosine phosphorylation), and participate in nonlinear signaling pathways (e.g., exhibiting switch-like behavior). Several hypotheses to explain the origin of these nonlinearities fall under the broad hypothesis that

Photosynthetic light-harvesting complexes of higher plants, moss and green algae can undergo dynamic conformational transitions, which have been correlated to their ability to adapt to fluctuations in the light environment. Herein, we demonstrate the application of solid-state NMR spectroscopy on native, heterogeneous thylakoid membranes of Chlamydomonas reinhardtii (Cr) and on Cr Light-Harvesting

DNA sequences in regulatory regions and in telomers at the ends of chromosomes frequently contain tandem repeats of guanine nucleotides that can form stacked structures stabilized by Hoogsten pairing and centrally bound monovalent cations. The replication and elongation of telomeres requires the disruption of these G-quadruplex structures. Hence, drug molecules such as gold(Au)-carbene that stabilize

During cellular respiration, radicals, such as superoxide, are produced, and in a large concentration, they may cause cell damage. To combat this threat, the cell employs the enzyme Cu/Zn Superoxide Dismutase (SOD1), which converts the radical superoxide into molecular oxygen and hydrogen peroxide, through redox reactions. Although this is its main function, recent studies have shown that the SOD1

Chemoprevention failure is considered to be the most emerging problem that makes non-small cell lung cancer (NSCLC) as one of the deadliest malignancies in the world. In NSCLC cells, Nuclear factor erythroid 2-related factor 2 (Nrf2), a redox sensitive transcription factor, promotes cancer cell survival and fosters mechanism for drug resistance. Here we report identification of Kaempferol, a dietary

Circadian clock genes are found in almost every cell that has a nucleus; they regulate the rhythmic nature of all processes that are cyclical. Among the genes controlled by the circadian clock, there are numerous factors that regulate key processes in the functioning of the cell. Disturbances in the functioning of the circadian clock are associated with numerous disorders. A recent study has shown

Micro–ribonucleic acids (miRNAs) are a class of conserved small non-coding RNAs (sncRNAs) that post-transcriptionally regulate their downstream target genes. Existing evidence indicates that abnormal expression of mRNAs results in the occurrence and development of pancreatic cancer (PC). In this study, we explored the potential role of miRNA-139 (miR-139) as a biomarker in the monitoring and treatment

Objectively assessing horse movement symmetry as an adjunctive to the routine lameness evaluation is on the rise with several commercially available systems on the market. Prerequisites for quantifying such symmetries include knowledge of the gait and gait events, such as hoof to ground contact patterns over consecutive strides. Extracting this information in a robust and reliable way is essential

Sex and joint injury are risk factors implicated in the onset and progression of osteoarthritis (OA). In mouse models of post-traumatic OA (ptOA), the pathogenesis of disease is notably impacted by sex (often worse in males) and injury model (e.g. meniscal versus ligament injury). Increasing ptOA progression and severity is often associated with greater relative instability of the joint but few studies

Knee osteoarthritis is a leading cause of ambulatory disability in adults. The most prescribed mobility aid, the walking cane, is often underloaded and therefore fails to reduce knee joint loading and provide symptomatic relief. For this study, a novel walking cane with haptic biofeedback was designed to improve cane loading and reduce the knee adduction moment (KAM). To determine; 1) the short-term

The active control of the trunk plays an important role in frontal plane gait stability. We characterized trunk control in response to different step widths using a novel feedback system and examined the different effects of wide and narrow step widths as they each present unique task demands. Twenty healthy young adults walked on a treadmill at 1.25 m/s at five prescribed step widths: 0.33, 1.67,

Prostate cancer exhibits a propensity to metastasize to the bone, which often leads to fatality. Bone metastasis is characterized by complex biochemical, morphological, pathophysiological, and genetic changes to cancer cells as they colonize at bone sites. In this study, we report the evaluation of MDA PCa2b prostate cancer cells' nanomechanical properties during the mesenchymal-to-epithelial transition

Noroviruses cause immense frequent, sporadic gastroenteritis outbreaks worldwide. Emerging genotypes, which are divided based on VP1 sequence, further enhance this public threat. Self-assembling properties of the human norovirus major capsid protein VP1 are crucial for using virus-like particles (VLPs) for vaccine development. However, there is no vaccine available yet. Here, VLPs from different variants

Chromatosomes play a fundamental role in chromatin regulation, but a detailed understanding of their structure is lacking, partially due to their complex dynamics. Using single-molecule DNA unzipping with optical tweezers, we reveal that linker histone interactions with DNA are remarkably extended, with the C-terminal domain binding both DNA linkers as far as ~ ±140 bp from the dyad. In addition to

Light-field microscopy has emerged as a technique of choice for high-speed volumetric imaging of fast biological processes. However, artefacts, non-uniform resolution, and a slow reconstruction speed have limited its full capabilities for in toto extraction of the dynamic spatiotemporal patterns in samples. Here, we combined a view-channel-depth (VCD) neural network with light-field microscopy to mitigate

In this work, we present a single pole magnetic tweezers (MT) device designed for integration with substrate deformation tracking microscopy (DTM) and/or traction force microscopy (TFM) experiments intended to explore extracellular matrix rheology and human epidermal keratinocyte mechanobiology. Assembled from commercially available off-the-shelf electronics hardware and software, the MT device is

In this work we demonstrate the integration of magnetic tweezers (MT) with substrate deformation tracking microscopy (DTM) and traction force microscopy (TFM) for the investigation of extracellular matrix rheology and human epidermal keratinocyte mechanobiology in the context of human blistering skin diseases. Two model bead on gel experiments are described in which an MT device is used to apply a

Experimental evidence has demonstrated the potential of transient pulses of electric fields to alter mammalian cell phenotypes. Strategies with these pulsed electric fields (PEFs) have been developed for clinical applications in cancer therapeutics, in-vivo decellularization, and tissue regeneration. Successful implementation of these strategies involves understanding how PEFs impact the cellular structures

Cell penetration after recognition of the SARS-CoV-2 virus by the ACE2 receptor, and the fusion of its viral envelope membrane with cellular membranes, are the early steps of infectivity. A region of the Spike protein (S) of the virus, identified as the fusion peptide (FP), is liberated at its N-terminal site by a specific cleavage occurring in concert with the interaction of the receptor binding domain

Live cell imaging is used to track the dynamic adaptation of cell size and motility to various external factors. Bright field configuration can be used for these experiments, however the analysis can be challenging and difficult to automate. In this direction, a superior alternative is represented by the use of live‐cell dyes, which provide intense fluorescence from subcellular structures of living

Glucuronoxylans represent a significant fraction of woody biomass, and its decomposition is complicated by presence of lignin‐carbohydrate complexes (LCCs). Herein, LCCs from birchwood were used to investigate the potential coordinated action of a glucuronoyl esterase (TtCE15A) and two α‐glucuronidases, (SdeAgu115A and AxyAgu115A). When supplementing α‐glucuronidase with equimolar quantities of TtCE15A

ABSTRACT This pilot study’s goal was to investigate the impacts of static magnetic fields (SMF) on finger skin blood perfusion (SBP) when exposing the ulnar artery and ulnar and medial nerves to a rare earth concentric magnet for 30 minutes. Control SBP was measured in 4th fingers of adults (n = 12, age 26.0 ± 1.4 years) for 15 minutes using laser-Doppler. Then, active-magnets were placed over one

ATP-dependent DEAD-box helicases constitute one of the largest families of RNA helicases and are important regulators of most RNA-dependent cellular processes. The functional core of these enzymes consists of two RecA-like domains. Changes in the interdomain orientation of these domains upon ATP and RNA binding result in the unwinding of double-stranded RNA. The DEAD-box helicase DbpA from E. coli

Background Iron excess is a risk factor for cardiovascular diseases and it is important to understand the effect of iron on vascular permeability, particularly for the transport of large metabolic hormones such as adiponectin. Methods We used 2-dimensional monolayers of cultured human dermal microvascular endothelial cells (HDMEC) and human umbilical vein endothelial cells (HUVEC) as well as 3-dimensional

Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine, the aetiology and pathogenesis of which are poorly understood. Unfortunately, biomechanical data describing trunk muscle activation and intervertebral load, which can contribute to understanding the pathomechanics of the AIS spine, cannot be measured in vivo due to the invasiveness of the procedures. The present study

Older adults typically demonstrate reductions in overground walking speeds and propulsive forces compared to young adults. These reductions in walking speeds are risk factors for negative health outcomes. Therefore, this study aimed to determine the effect of an adaptive speed treadmill controller on walking speed and propulsive forces in older adults, including the mechanisms and strategies underlying

Achieving lateral integration of articular cartilage repair tissue with surrounding native cartilage remains a clinical challenge. Histological and bulk mechanical studies have identified extracellular matrix components that correlate with superior failure strength, but it is unclear how local changes in geometry and composition at the repair interface affect tissue strains under physiologic loading

Assessment of scapulothoracic and glenohumeral contributions to shoulder function during baseball pitching are limited by challenges in accurately measuring dynamic scapular orientation. A recently validated individualized linear model approach that estimates scapular orientation based on measurable humerothoracic orientation has yet to be adapted for pitching and may improve upon currently recommended

The UVA and UVB components of sunlight can produce three classes of bipyrimidine DNA photolesions [cyclobutane pyrimidine dimers (CPDs), pyrimidine (6‐4) pyrimidone photoproducts (6‐4PPs) and related Dewar valence isomers (DewarPPs)]. The UVA/UVB ratio of sunlight is high in winter and low in summer in the Northern Hemisphere. Since UVB radiation produces 6‐4PPs and UVA radiation converts them into

Incorporation of non-canonical amino acids (ncAAs) can endow proteins with novel functionalities, such as crosslinking or fluorescence. In ion channels, the function of these variants can be studied with great precision using standard electrophysiology, but this approach is typically labor intensive and low throughput. Here, we establish a high-throughput protocol to conduct functional and pharmacological

While there is a prevalent genome organization in eukaryotic cells, with heterochromatin concentrated at the nuclear periphery, anomalous cases do occur. Deviations of chromatin distribution are frequent, for example, upon aging, under malignant diseases, or even naturally in rod cells of nocturnal mammals. Using molecular dynamic simulations, we study the segregation of heterochromatin in the cell

Phospholipids, which are an integral component of cell membranes, exhibit a rich variety of lamellar phases modulated by temperature and composition. Molecular dynamics (MD) simulations have greatly enhanced our understanding of phospholipid membranes by capturing experimentally observed phases and phase transitions at molecular resolution. However, the ripple membrane phase, observed as an intermediate

We develop a model of latch-mediated spring actuated (LaMSA) systems relevant to comparative biomechanics. The model contains five components: two motors (muscles), a spring, a latch, and a load mass. One motor loads the spring to store elastic energy, and the second motor subsequently removes the latch, which releases the spring and causes movement of the load mass. We develop open-source software

The identification of stabilizing amino acid substitutions in proteins is a key challenge in protein engineering. Advances in biotechnology have enabled assaying of thousands of protein variants in a single high-throughput experiment, and more recent studies use such data in protein engineering. We present a Global Multi-Mutant Analysis (GMMA) that exploits the presence of multiply-substituted variants

We present a theoretical method to study how changes in pH shape the heterogeneous conformational ensemble explored by intrinsically disordered proteins (IDPs). The theory is developed in the context of coarse-grained models, which enable a fast, accurate, and extensive exploration of conformational space at a given protonation state. In order to account for pH effects, we generalize the Molecular

Circular dichroism spectroscopy is a structural biology technique frequently applied to determine the secondary structure composition of soluble proteins. Our recently introduced computational analysis package SESCA aids the interpretation of protein circular dichroism spectra and enables the validation of proposed corresponding structural models. To further these aims, we present the implementation

The complex glycans comprising ‘dietary fiber’ evade the limited repertoire of human digestive enzymes and hence feed the vast community of microbes in the lower gastrointestinal tract. As such, complex glycans drive the composition of the human gut microbiota and, in turn, influence diverse facets of our nutrition and health. To access these otherwise recalcitrant carbohydrates, gut bacteria produce

ABCB1, also called MDR1 or P‐glycoprotein, exports various hydrophobic compounds and plays an essential role as a protective physiological barrier in several organs, including the brain, testis, and placenta. However, little is known about the structural mechanisms that allow ABCB1 to recognize hydrophobic compounds of diverse structures or the coupling of ATP hydrolysis to uphill substrate export

In Escherichia coli, DNA replication is restarted following DNA repair by the PriA‐dependent pathway, in which the binding and dissociation of proteins such as PriA, PriB, and DnaT on ssDNA lead to the formation of a protein–DNA complex for recruiting the DnaB–DnaC replication protein complex. However, the structure of the PriB–DnaT complex, which is an essential step in the PriA‐dependent pathway

ATP binding cassette (ABC) transporter proteins include efflux pumps that confer multixenobiotic resistance to zebrafish embryos, a valuable toxico/pharmacological model. Here, we established an automated microscopy‐based rhodamine B dye accumulation assay in which enhanced dye accumulation in live zebrafish embryos indicates inhibition of multixenobiotic efflux transporter activity. Twenty structurally