Quasi-harmonic analysis of mode coupling in fluctuating native proteins

Mode coupling and anharmonicity in a native fluctuating protein are investigated in modal space by projecting the motion along the eigenvectors of the fluctuation correlation matrix. The probability distribution of mode fluctuations is expressed in terms of tensorial Hermite polynomials. Molecular dynamics trajectories of Crambin are generated and used to evaluate the terms of the polynomials and to obtain the modal energies. The energies of a few modes exhibit large deviations from the harmonic energy of kT/2 per mode, resulting from coupling to the surroundings, or to another specific mode or to several other modes. Slowest modes have energies that are below that of the harmonic, and a few fast modes have energies significantly larger than the harmonic. Detailed analysis of the coupling of these modes to others is presented in terms of the lowest order two-mode coupling terms. Finally, the effects of mode coupling on conformational properties of the protein are investigated.     

Quercetin-loaded platelets as a potential targeted therapy for glioblastoma multiforme cell line U373-MG

Over the globe, the incidence of glioblastoma multiforme (GM) is very low, that is, 1–4 cases per 100,000, but it is fatal and cancer grows very fast inside the brain tissues, namely astrocytes and oligodendrocytes. Because of the rapid growth, it is difficult to halt the dissemination of tumor in adjacent tissues. Although temozolomide (TMZ) is a currently approved standard of care, it develops resistance over the period. Therefore, there is a need to develop a novel drug delivery system. In this work, authors have developed platelets as drug delivery carriers-loaded with quercetin (QCT) for targeting GM. The effect of QCT and QCT-platelet was assessed on the U373-MG cell line. Natural human platelets were used as carriers for drug loading and drug delivery. Platelets possess an open canalicular system that allows the uptake of drug molecules in the platelet cytoplasm. The study showed that the maximum encapsulation efficiency of QCT-platelet was 93.96 ± 0.12% and the maximum drug release in 24 h was 76.26 ± 0.13% in-vitro at pH 5.5 that mimics the tumor microenvironment. In this work, there is a three-fold enhancement of solubility of QCT. The cytotoxic activity of QCT-platelets was studied in the U373-MG human astrocytoma glioblastoma cell line and the cell viability was 14.52 ± 1.53% after 48 h. Thus, platelets were proved as good carriers for therapeutic moieties and can be effectively used to target the glioblastoma tumor in the near future.     

Designing and Judd–Ofelt evaluation of versatile luminescent Eu (III) complexes sensitized with β-diketone ligand for multifarious applications

The present research work entails the synthesis of one binary and four ternary red light−emitting Eu (III)-based complexes with 3-benzylidene-2,4-pentanedione as the main ligand and 1,10-phenanthroline, bathophenanthroline, neocuproine, and 4,4′-′dimethyl-2,2′-′bipyridyl as auxiliary ligands. The metal–organic framework of the series was elucidated using energy dispersive X-ray analysis, elemental analysis, Fourier transform infrared spectroscopy, and proton nuclear magnetic resonance. This Eu (III) series exhibits optimum thermal stability, making them a promising candidate for organic light-emitting diodes. On the basis of emission spectra, their optical parameters such as nonradiative and radiative decay rates, luminescence decay time, intrinsic quantum efficiency, and Judd–Ofelt intensity parameter were determined. The monocentric luminescence and Judd–Ofelt parameters reveal the absence of symmetry around the europium center. CIE chromaticity coordinates, correlated color temperature values, color purity, and asymmetric ratios authenticate the color coordinates of the complexes in red region. Optical band gap values lie within the range of wide band gap semiconductors, indicating their utilization in military radars and biological labeling.     

Self-incompatibility: a targeted,unexplored pre-fertilization barrier in flower crops of Asteraceae

Journal of Plant Research - Asteraceae (synonym as Compositae) is one of the largest angiosperm families among flowering plants comprising one-tenth of all agri-horticultural species grown across...     

Molecular analysis of the sea anemone toxin Av3 reveals selectivity to insects and demonstrates the heterogeneity of receptor site-3 on voltage-gated Na+ channels

Most known organisms encode proteases that are crucial for constitutive proteolytic events. In the present paper, we describe a method to define these events in proteomes from Escherichia coli to humans. The method takes advantage of specific N-terminal biotinylation of protein samples, followed by affinity enrichment and conventional LC (liquid chromatography)-MS/MS (tandem mass spectrometry) analysis. The method is simple, uses conventional and easily obtainable reagents, and is applicable to most proteomics facilities. As proof of principle, we demonstrate profiles of proteolytic events that reveal exquisite in vivo specificity of methionine aminopeptidase in E. coli and unexpected processing of mitochondrial transit peptides in yeast, mouse and human samples. Taken together, our results demonstrate how to rapidly distinguish real proteolysis that occurs in vivo from the predictions based on in vitro experiments.     

Paraoxonase and arylesterase activities in fibromyalgia

We aimed to evaluate the association of serum paraoxonase and arylesterase activities and oxidative/antioxidative status in patients with fibromyalgia. Forty-two patients with fibromyalgia and 53 healthy controls were included in the study. Serum paraoxonase and arylesterase activities were measured spectrophotometrically. Oxidative and antioxidative status were evaluated by measuring serum lipid hydroperoxide (LOOH) levels, total antioxidant status (TAS) and free sulfhydryl groups (-SH = total thiol). Lipid parameters were determined by routine laboratory methods. Serum paraoxonase and arylesterase activities, and TAS were lower in patients with fibromyalgia than in controls (P < 0.001, for all), and the -SH level was also lower in the patient group (P = 0.03). LOOH levels were higher in the patient group than in controls (P = 0.01). Our results suggest that patients with fibromyalgia were exposed to oxidative stress, and paraoxonase and arylesterase activities were decreased in these patients. Patients with fibromyalgia might be prone to development of atherosclerosis with reduced paraoxonase and arylesterase activities.     

The impact of infliximab treatment on quality of life in patients with inflammatory rheumatic diseases

In this study, we compare the health-related quality of life (HRQoL) of patients with moderate-to-severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), and study the effect of treatment with infliximab on the HRQoL of patients with these diseases. Short Form Health Survey-36 (SF-36) data from the placebo-controlled phases of 4 studies of infliximab in patients with inflammatory rheumatic diseases (n = 1990) were evaluated. Data came from the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) (n = 428), the Safety Trial for Rheumatoid Arthritis with REMICADE Therapy (START) (n = 1083), the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) (n = 279), and the Infliximab Multinational Psoriatic Arthritis Clinical Trial II (IMPACT II) (n = 200). SF-36 assessments were made at weeks 0, 10, 30, and 54 in ATTRACT, weeks 0, 6, and 22 in START, weeks 0, 12, and 24 in ASSERT, and weeks 0 and 14 in IMPACT II. All patient populations had significantly impaired physical aspects of HRQoL at baseline relative to the general population of the United States, and the magnitude of impairment was similar across the diseases. Mean baseline physical component summary scores were 29 in the RA cohort, 32 in the PsA cohort, and 29 in the AS cohort. In all 3 diseases, patients who received infliximab showed significant improvement in physical component summary scores compared with those who received placebo. The magnitude of the difference of improvement (effect size, 95%CI) between infliximab and placebo groups was similar in the AS (10.1, 9.2–11.0), PsA (8.6, 7.8–9.4), and RA (10.1, 9.2–11.0) cohorts. Patients with RA and those with PsA treated with infliximab also showed greater improvement in the mental component summary score than those in the placebo group with an effect size of 4.6 (4.2–5.1) in RA and 2.7 (2.4–3.1) in PsA. Patients in large randomized controlled studies of infliximab in RA, PsA, and AS had similar impairment in physical aspects of HRQoL at baseline and showed significantly greater improvement in HRQoL after treatment with infliximab.     

A family of amphiphilic dioxidovanadium(V) hydrazone complexes as potent carbonic anhydrase inhibitors along with anti-diabetic and cytotoxic activities

BioMetals - A family of dioxidovanadium(V) complexes (1–4) of the type [Na(H2O)x]+[VVO2(HL1?4)]? (x?=?4, 4.5 and 7) where HL2? represents the dianionic form of...     

Chronic granulomatous disease: a review of the infectious and inflammatory complications

Chronic Granulomatous Disease is the most commonly encountered immunodeficiency involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. The disease is the result of a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms. This can lead to infections with Staphylococcus aureus, Psedomonas species, Nocardia species, and fungi (such as Aspergillus species and Candida albicans). Involvement of vital or large organs can contribute to morbidity and/or mortality in the affected patients. Major advances have occurred in the diagnosis and treatment of this disease, with the potential for gene therapy or stem cell transplantation looming on the horizon.