Vasti

Layered double hydroxides nanoparticles (LDH-NP) are increasingly studied for biomedical applications. Nevertheless, their interaction with biomolecules such as proteins needs further exploration for an effective application. In this work, the adsorption of bovine serum albumin (BSA) on LDH-NP and the conformation changes of the protein upon adsorption were characterized using fluorescence spectroscopy. First, the quenching of tryptophan residues of BSA by chloride-intercalated LDH-NP was explored and the BSA adsorption capacity of LDH-NP were determined...

Cerebral palsy (CP) is a neurologic injury that impacts control of movement. Individuals with CP also often develop secondary impairments like weakness and contracture. Both altered motor control and secondary impairments influence how an individual walks after neurologic injury. However, understanding the complex interactions between and relative effects of these impairments makes analyzing and improving walking capacity in CP challenging. We used a sagittal-plane musculoskeletal model and neuromuscular control framework to simulate crouch and nondisabled gait...

Introduction: Spaceflight is associated with substantial and variable musculoskeletal (MSK) adaptations. Characterisation of muscle and joint loading profiles can provide key information to better align exercise prescription to astronaut MSK adaptations upon return-to-Earth. A case-study is presented of single-leg hopping in hypogravity to demonstrate the additional benefit computational MSK modelling has when estimating lower-limb MSK loading. Methods: A single male participant performed single-leg vertical hopping whilst attached to a body weight support system to replicate five gravity conditions (0...

Alterations in RNA-splicing are a molecular hallmark of several neurological diseases, including muscular dystrophies where mutations in genes involved in RNA metabolism or characterised by alterations in RNA splicing have been described. Here, we present five patients from two unrelated families with a limb-girdle muscular dystrophy (LGMD) phenotype carrying a biallelic variant in SNUPN gene. Snurportin-1, the protein encoded by SNUPN, plays an important role in the nuclear transport of small nuclear ribonucleoproteins (snRNPs), essential components of the spliceosome...

Two new copper dimers, namely, bis-(dimethyl sulfoxide)-tetra-kis-(μ-pyrene-1-carboxyl-ato)dicopper( Cu - Cu ), [Cu2 (C17 H9 O2 )4 (C2 H6 OS)2 ] or [Cu2 (pyr-COO- )4 (DMSO)2 ] ( 1 ), and bis-(di-methyl-formamide)-tetra-kis-(μ-pyrene-1-carboxyl-ato)dicopper( Cu - Cu ), [Cu2 (C17 H9 O2 )4 (C3 H7 NO)2 ] or [Cu2 (pyr-COO- )4 (DMF)2 ] ( 2 ) (pyr = pyrene), were synthesized from the reaction of pyrene-1-carb-oxy-lic acid, copper(II) nitrate and tri-ethyl-amine from solvents DMSO and DMF, respectively...

We talk to Vasty Osei Amponsa and Kylie J. Walters about their paper "hRpn13 shapes the proteome and transcriptome through epigenetic factors HDAC8, PADI4, and transcription factor NF-κB p50", their journeys across continents leading them to the NCI, and how Kylie tries to foster curiosity and a sense of belonging in her lab.

The anti-cancer target hRpn13 is a proteasome substrate receptor. However, hRpn13-targeting molecules do not impair its interaction with proteasomes or ubiquitin, suggesting other critical cellular activities. We find that hRpn13 depletion causes correlated proteomic and transcriptomic changes, with pronounced effects in myeloma cells for cytoskeletal and immune response proteins and bone-marrow-specific arginine deiminase PADI4. Moreover, a PROTAC against hRpn13 co-depletes PADI4, histone deacetylase HDAC8, and DNA methyltransferase MGMT...

Mycobacterium tuberculosis is the main causal agent of pulmonary tuberculosis (TB); the treatment of this disease is long and involves a mix of at least four different antibiotics that frequently lead to abandonment, favoring the surge of drug-resistant mycobacteria (MDR-TB), whose treatment becomes more aggressive, being longer and more toxic. Thus, the search for novel strategies for treatment that improves time or efficiency is of relevance. In this work, we used a murine model of pulmonary TB produced by the MDR-TB strain to test the efficiency of gene therapy with adenoviral vectors codifying TNF (AdTNF), a pro-inflammatory cytokine that has protective functions in TB by inducing apoptosis, granuloma formation and expression of other Th1-like cytokines...

Joint compressive forces have been identified as a risk factor for osteoarthritis disease progression. Therefore, unloader braces are a common treatment with the aim of relieving pain, but their effects are not clearly documented in the literature. A knee brace concept was tested with the aim of reducing joint loads and pain in knee osteoarthritis patients by applying an extension moment exclusively during the stance phase. The ideal effects were evaluated during gait based on musculoskeletal modeling of six patients, and experimental tests with a prototype brace were conducted on one patient...

The objective of the study was to explore how biarticular mechanisms of the gastrocnemii muscles may provide an important energy source for power and work at the ankle joint with increasing running speed. Achilles tendon force was quantified as a proxy of the triceps surae muscle force and the contribution of the monoarticular soleus and the biarticular gastrocnemii to the mechanical power and work performed at the ankle joint was investigated in three running speeds (transition 2.0 m s-1 , slow 2.5 m s-1 , fast 3...

Goodman, WW, Helms, E, and Graham, DF. Individual muscle contributions to the acceleration of the center of mass during the barbell back squat in trained female subjects. J Strength Cond Res 37(10): 1947-1954, 2023-The squat is used to enhance performance and rehabilitate the lower body. However, muscle forces and how muscles accelerate the center of mass (CoM) are not well understood. The purpose was to determine how lower extremity muscles contribute to the vertical acceleration of the CoM when squatting to parallel using 85% one-repetition maximum...

OBJECTIVES: Compare lower extremity muscle volume in females with patellofemoral pain (PFP) to a cohort of pain-free females and investigate the relationship between thigh and hip muscle volume and torque. DESIGN: Cross-sectional. PARTICIPANTS: Twenty-one females, 13 with PFP and 8 pain-free controls. MAIN OUTCOME MEASURES: We quantified normalized lower extremity muscle volume (cm3 /kg*m) via magnetic resonance imaging and isometric hip and thigh torque (Nm/kg) via a multimodal dynamometer...

Tuberculosis (TB) is the deadliest disease caused by a bacterial agent. Glucocorticoids (GCs) have a typical anti-inflammatory effect, but recently it has been shown that they can present proinflammatory activity, mainly by increasing molecules from innate immunity. In the current study, we evaluated the effect of low doses of dexamethasone on Mycobacterium tuberculosis in vivo and in vitro. We used an established mice model of progressing tuberculosis (TB) in the in vivo studies. Intratracheal or intranasal dexamethasone therapy administered with conventional antibiotics in the late stage of the disease decreased the lung bacilli load and lung pneumonia, and increased the survival of the animals...

Regulated protein degradation in eukaryotes is performed by the 26S proteasome, which contains a 28-subunit hollow core particle (CP) within which proteolysis occurs, and a 19-subunit regulatory particle (RP) that binds, processes, and translocates substrates to the CP. In addition to its intrinsic subunits, myriad proteins interact with the proteasome transiently, including factors that assist and/or regulate its degradative activities. Efforts to identify proteasome-interacting components and/or to solve its structure have relied on over-expression of a tagged plasmid, establishing stable cell lines, or laborious purification protocols to isolate native proteasomes from cells...

Tuberculosis (TB) caused by the complex Mycobacterium tuberculosis (Mtb) is the main cause of death by a single bacterial agent. Last year, TB was the second leading infectious killer after SARS-CoV-2. Nevertheless, many biological and immunological aspects of TB are not completely elucidated, such as the complex process of immunoregulation mediated by regulatory T cells (Treg cells) and the enzymes indoleamine 2,3-dioxygenase (IDO) and heme oxygenase 1 (HO-1). In this study, the contribution of these immunoregulatory factors was compared in mice infected with Mtb strains with different levels of virulence...

OBJECTIVE: Characterise the diagnostic and prognostic value of muscle MRI patterns as biomarkers in a genetically heterogeneous nemaline myopathy (NM) patient cohort. METHODS: Modified Mercuri scoring of lower limb MRI in genetically characterised NM patients referred to the highly specialised service for congenital myopathies at Great Ormond Street Hospital. Findings were compared to clinical data and MRI patterns derived from collated published data. RESULTS: Twenty-seven patients with MRI were identified (8 NEB-NM, 13 ACTA1-NM, 6 TPM3-NM)...

Trauma-related psychopathology transpires in some individuals after exposure to a life-threatening event. While aberrant adrenergic processes may contribute to this, a clear understanding of how said processes influence trauma-related conditions, remain inadequate. Here, we aimed to develop and describe a novel zebrafish (Danio rerio) model of life-threatening trauma-induced anxiety that may be representative of trauma related anxiety, and to evaluate the impact of stress-paired epinephrine (EPI) exposure in the model system...

Knowledge of individual muscle force during strength and conditioning exercises provides deeper understanding of how specific training decisions relate to desired training outcomes. The purpose of this study was to estimate individual muscle forces during hexbar jumps with 0%, 20%, 40%, and 60% of the hexbar deadlift 1-repetition maximum utilizing in vivo motion capture and computational modeling techniques of male participants. Muscle forces for the gluteus maximus, biceps femoris, rectus femoris, vastus intermedius, gastrocnemius, and soleus were estimated via static optimization...

Understanding the mechanical demands of an exercise on the musculoskeletal system is crucial to prescribe effective training or therapeutic interventions. Yet, that knowledge is currently limited in water, mostly because of the difficulty in evaluating external resistance. Here I reconcile recent advances in 3D markerless pose and mesh estimation, biomechanical simulations, and hydrodynamic modeling, to predict lower limb mechanical loading during aquatic exercises. Simulations are driven exclusively from a single video...

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To compare muscle size, body composition, bone mineral density (BMD), and metabolic profiles in denervated versus innervated individuals with spinal cord injury (SCI). SETTING: Hunter Holmes McGuire Veterans Affairs (VA) Medical Center. METHODS: Body composition, bone mineral density (BMD), muscle size, and metabolic parameters were collected in 16 persons with chronic SCI (n = 8 denervated, n = 8 innervated) using dual-energy x-ray absorptiometry (DXA), magnetic resonance imaging (MRI), and fasting blood samples...