Thermodynamically based DNA strand design

We describe a new algorithm for design of strand sets, for use in DNA computations or universal microarrays. Our algorithm can design sets that satisfy any of several thermodynamic and combinatorial constraints, which aim to maximize desired hybridizations between strands and their complements, while minimizing undesired cross-hybridizations. To heuristically search for good strand sets, our algorithm uses a conflict-driven stochastic local search approach, which is known to be effective in solving comparable search problems. The PairFold program of Andronescu et al. [M. Andronescu, Z. C. Zhang and A. Condon (2005) J. Mol. Biol., 345, 987–1001; M. Andronescu, R. Aguirre-Hernandez, A. Condon, and H. Hoos (2003) Nucleic Acids Res., 31, 3416–3422.] is used to calculate the minimum free energy of hybridization between two mismatched strands. We describe new thermodynamic measures of the quality of strand sets. With respect to these measures of quality, our algorithm consistently finds, within reasonable time, sets that are significantly better than previously published sets in the literature

Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) comprise a group of illnesses marked by memory and behavioral dysfunction that can occur in up to 50% of HIV patients despite adequate treatment with combination antiretroviral drugs. Iron dyshomeostasis exacerbates HIV-1 infection and plays a major role in Alzheimer’s disease pathogenesis. In addition, persons living with HIV demonstrate a high prevalence of neurodegenerative disorders, indicating that HAND provides a unique opportunity to study ferroptosis in these conditions. Both HIV and combination antiretroviral drugs increase the risk of ferroptosis by augmenting ferritin autophagy at the lysosomal level. As many viruses and their proteins exit host cells through lysosomal exocytosis, ferroptosis-driving molecules, iron, cathepsin B and calcium may be released from these organelles. Neurons and glial cells are highly susceptible to ferroptosis and neurodegeneration that engenders white and gray matter damage. Moreover, iron-activated microglia can engage in the aberrant elimination of viable neurons and synapses, further contributing to ferroptosis-induced neurodegeneration. In this mini review, we take a closer look at the role of iron in the pathogenesis of HAND and neurodegenerative disorders. In addition, we describe an epigenetic compensatory system, comprised of bromodomain-containing protein 4 (BRD4) and microRNA-29, that may counteract ferroptosis by activating cystine/glutamate antiporter, while lowering ferritin autophagy and iron regulatory protein-2. We also discuss potential interventions for lysosomal fitness, including ferroptosis blockers, lysosomal acidification, and cathepsin B inhibitors to achieve desirable therapeutic effects of ferroptosis-induced neurodegeneration

Free energy estimation of short DNA duplex hybridizations

<p>Abstract</p> <p>Background</p> <p>Estimation of DNA duplex hybridization free energy is widely used for predicting cross-hybridizations in DNA computing and microarray experiments. A number of software programs based on different methods and parametrizations are available for the theoretical estimation of duplex free energies. However, significant differences in free energy values are sometimes observed among estimations obtained with various methods, thus being difficult to decide what value is the accurate one.</p> <p>Results</p> <p>We present in this study a quantitative comparison of the similarities and differences among four published DNA/DNA duplex free energy calculation methods and an extended Nearest-Neighbour Model for perfect matches based on triplet interactions. The comparison was performed on a benchmark data set with 695 pairs of short oligos that we collected and manually curated from 29 publications. Sequence lengths range from 4 to 30 nucleotides and span a large GC-content percentage range. For perfect matches, we propose an extension of the Nearest-Neighbour Model that matches or exceeds the performance of the existing ones, both in terms of correlations and root mean squared errors. The proposed model was trained on experimental data with temperature, sodium and sequence concentration characteristics that span a wide range of values, thus conferring the model a higher power of generalization when used for free energy estimations of DNA duplexes under non-standard experimental conditions.</p> <p>Conclusions</p> <p>Based on our preliminary results, we conclude that no statistically significant differences exist among free energy approximations obtained with 4 publicly available and widely used programs, when benchmarked against a collection of 695 pairs of short oligos collected and curated by the authors of this work based on 29 publications. The extended Nearest-Neighbour Model based on triplet interactions presented in this work is capable of performing accurate estimations of free energies for perfect match duplexes under both standard and non-standard experimental conditions and may serve as a baseline for further developments in this area of research.</p

Acoustic radiation force imaging sonoelastography for noninvasive staging of liver fibrosis

AIM: To investigate the diagnostic accuracy of acoustic radiation force impulse (ARFI) imaging as a noninvasive method for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients

Collagen-Nanoparticles Composites for Wound Healing and Infection Control

Nowadays, the world is facing a serious crisis represented by the rapid emergence of resistant bacteria, which jeopardizes the efficacy of antibiotics. This crisis has been attributed to the overuse and misuse of antibiotics, as well as the cessation of new drug production by the pharmaceutical industry. Therefore, bacterial strains with resistance to multiple antibiotic classes have appeared, such as Staphylococcus aureus, Acinetobacter spp. and Pseudomonas aeruginosa. This review aims to provide an updated summary of the current approach to the treatment of infections due to resistant microorganisms, with a focus on the application of the antimicrobial effects of inorganic nanoparticles in combination with collagen to promote wound healing. In addition, the paper describes the current approaches in the field of functionalized collagen hydrogels capable of wound healing and inhibiting microbial biofilm production

Influence of Polymer Shell Molecular Weight on Functionalized Iron Oxide Nanoparticles Morphology and In Vivo Biodistribution

Iron oxide nanoparticles (IONPs) have been extensively used in different biomedical applications due to their biocompatibility and magnetic properties. However, different functionalization approaches have been developed to improve their time-life in the systemic circulation. Here, we have synthesized IONPs using a modified Massart method and functionalized them in situ with polyethylene glycol with different molecular weights (20 K and 35 K). The resulting nanoparticles were characterized in terms of morphology, structure, and composition using transmission electron microscopy (TEM) and selected area electron diffraction (SAED). In vivo biodistribution was evaluated in Balb/c mice, the presence of IONP being evidenced through histopathological investigations. IONP morphological characterization showed a change in shape (from spherical to rhombic) and size with molecular weight, while structural characterization proved the obtaining of highly crystalline samples of spinel structured cubic face-centered magnetite. In vivo biodistribution in a mice model proved the biocompatibility of all of the IONP samples. All NPs were cleared through the liver, spleen, and lungs, while bare IONPs were also evidenced in kidneys