Complete Genome Sequences of Subcluster C1 Mycobacteriophages Blackbrain, Cactojaque, Kboogie, Trinitium, and YoungMoneyMata.

Five subcluster C1 mycobacteriophages, Blackbrain, Cactojaque, Kboogie, Trinitium, and YoungMoneyMata, were isolated from soil using the host Mycobacterium smegmatis mc2155. The genome sizes range from 154,512 to 156,223 bp. The largest genome encodes 237 predicted proteins, 34 tRNAs, and 1 transfer-messenger RNA (tmRNA).

Complete Genome Sequences of Mycobacteriophages SynergyX, Abinghost, Bananafish, and Delton.

Four lytic mycobacteriophages, namely, SynergyX, Abinghost, Bananafish, and Delton, were isolated from soil in Washington, DC, using the bacterial host Mycobacterium smegmatis mc2155. Analysis of the genomes revealed that they belong to two subclusters of actinobacteriophage cluster B (subclusters B2 and B3) and subcluster D1 of cluster D.

Leishmaniasis: Recent epidemiological studies in the Middle East.

Leishmaniasis, one of the most neglected tropical diseases (NTDs), is the third most important vector-borne disease worldwide. This disease has a global impact and severity of the infection and is greatest in the Middle East. The agent of infection is a protozoan parasite of the genus, Leishmania, and is generally transmitted by blood-sucking female sandflies. In humans, there are three clinical forms of infection: (1) cutaneous (CL), (2) mucocutaneous (ML), and (3) visceral leishmaniasis (VL). This review aims to discuss the current epidemiological status of leishmaniasis in Saudi Arabia, Iraq, Syria, and Yemen with a consideration of treatment options. The elevated risk of leishmaniasis is influenced by the transmission of the disease across endemic countries into neighboring non-infected regions.

Correction to "An Investigation of the Interaction Between Bovine Serum Albumin-Conjugated Silver Nanoparticles and the Hydrogel in Hydrogel Nanocomposites".

[This corrects the article DOI: 10.1021/acsomega.1c00834.].

Complete Genome Sequences of Mycobacteriophages Dallas and Jonghyun.

Two temperate mycobacteriophages, Dallas and Jonghyun, were isolated from soil in Washington, DC, using the bacterial host Mycobacterium smegmatis mc2155. Analysis of the genomes revealed that Dallas and Jonghyun belong to clusters J and G, respectively. The structures of the genomes are typical of their respective clusters.

An Investigation of the Interaction between Bovine Serum Albumin-Conjugated Silver Nanoparticles and the Hydrogel in Hydrogel Nanocomposites.

Nanocomposite hydrogels are attracting significant interest due to their potential use in drug delivery systems and tissue scaffolds. Stimuli-responsive hydrogel nanocomposites are of particular interest due to sustained release of therapeutic agents from the hydrogel. However, challenges such as controlled release of therapeutic agents exist because of limited understanding of the interactions between the therapeutic agent and the hydrogel. To investigate the interaction, we synthesize a hydrogel nanocomposite by crosslinking the hydrogel precursors (tetrazine-modified polyethylene glycol and norbornene-modified hyaluronic acid) using click chemistry while bovine serum albumin-capped silver nanoparticles were encapsulated in situ in the matrix. The interaction between the nanoparticles and the hydrogel was studied by a combination of spectroscopic techniques. X-ray photoelectron spectroscopy results suggest that the hydrogel molecule rearranges so that polyethylene glycol is pointing up toward the surface while hyaluronic acid folds to interact with bovine serum albumin of the nanoparticles. Hyaluronic acid, facing inward, may interact with the nanoparticle via hydrogen bonding. The hydrogel nanocomposite showed antibacterial activity against Gram-positive/Gram-negative bactericides, supporting time-based nanoparticle release results. Our findings about interactions between the nanoparticles and the hydrogel can be useful in the formulation of next generation of hydrogel nanocomposites.

MK-STYX Alters the Morphology of Primary Neurons, and Outgrowths in MK-STYX Overexpressing PC-12 Cells Develop a Neuronal Phenotype.

We previously reported that the pseudophosphatase MK-STYX (mitogen activated kinase phosphoserine/threonine/tyrosine binding protein) dramatically increases the number of what appeared to be primary neurites in rat pheochromocytoma (PC-12) cells; however, the question remained whether these MK-STYX-induced outgrowths were bona fide neurites, and formed synapses. Here, we report that microtubules and microfilaments, components of the cytoskeleton that are involved in the formation of neurites, are present in MK-STYX-induced outgrowths. In addition, in response to nerve growth factor (NGF), MK-STYX-expressing cells produced more growth cones than non-MK-STYX-expressing cells, further supporting a model in which MK-STYX has a role in actin signaling. Furthermore, immunoblot analysis demonstrates that MK-STYX modulates actin expression. Transmission electron microscopy confirmed that MK-STYX-induced neurites form synapses. To determine whether these MK-STYX-induced neurites have pre-synaptic or post-synaptic properties, we used classical markers for axons and dendrites, Tau-1 and MAP2 (microtubule associated protein 2), respectively. MK-STYX induced neurites were dopaminergic and expression of both Tau-1 and MAP2 suggests that they have both axonal and dendritic properties. Further studies in rat hippocampal primary neurons demonstrated that MK-STYX altered their morphology. A significant number of primary neurons in the presence of MK-STYX had more than the normal number of primary neurites. Our data illustrate the novel findings that MK-STYX induces outgrowths in PC-12 cells that fit the criteria for neurites, have a greater number of growth cones, form synapses, and have pre-synaptic and post-synaptic properties. It also highlights that the pseudophosphatase MK-STYX significantly alters the morphology of primary neurons.

CD40-CD40L cross-talk drives fascin expression in dendritic cells for efficient antigen presentation to CD4+ T cells.

Fascin is an actin-bundling protein that, among immune cells, is restricted to expression in dendritic cells (DCs). Previous reports have suggested that fascin plays an important role in governing DC antigen presentation to CD4+ T cells. However, no report has clearly linked the receptor-ligand engagement that can direct downstream regulation of fascin expression. In this study, bone marrow-derived DCs from wild-type versus CD40-knockout C57BL/6 mice were used to elucidate the mechanisms of fascin expression and activity upon CD40-CD40 ligand (CD40L) engagement. These investigations now show that CD40 engagement governs fascin expression in DCs to promote CD4+ T-cell cytokine production. Absence of CD40 signaling resulted in diminished fascin expression in DCs and was associated with impaired CD4+ T-cell responses. Furthermore, the study found that loss of CD40-CD40L engagement resulted in reduced DC-T-cell contacts. Rescue by ectopic fascin expression in CD40-deficient DCs was able to re-establish sustained contacts with T cells and restore cytokine production. Taken together, these results show that cross-talk through CD40-CD40L signaling drives elevated fascin expression in DCs to support acquisition of full T-cell responses.

Novel drug design for Chagas disease via targeting Trypanosoma cruzi tubulin: Homology modeling and binding pocket prediction on Trypanosoma cruzi tubulin polymerization inhibition by naphthoquinone derivatives.

Chagas disease, also called American trypanosomiasis, is a parasitic disease caused by Trypanosoma cruzi (T. cruzi). Recent findings have underscored the abundance of the causative organism, (T. cruzi), especially in the southern tier states of the US and the risk burden for the rural farming communities there. Due to a lack of safe and effective drugs, there is an urgent need for novel therapeutic options for treating Chagas disease. We report here our first scientific effort to pursue a novel drug design for treating Chagas disease via the targeting of T. cruzi tubulin. First, the anti T. cruzi tubulin activities of five naphthoquinone derivatives were determined and correlated to their anti-trypanosomal activities. The correlation between the ligand activities against the T. cruzi organism and their tubulin inhibitory activities was very strong with a Pearson's r value of 0.88 (P value <0.05), indicating that this class of compounds could inhibit the activity of the trypanosome organism via T. cruzi tubulin polymerization inhibition. Subsequent molecular modeling studies were carried out to understand the mechanisms of the anti-tubulin activities, wherein, the homology model of T. cruzi tubulin dimer was generated and the putative binding site of naphthoquinone derivatives was predicted. The correlation coefficient for ligand anti-tubulin activities and their binding energies at the putative pocket was found to be r=0.79, a high correlation efficiency that was not replicated in contiguous candidate pockets. The homology model of T. cruzi tubulin and the identification of its putative binding site lay a solid ground for further structure based drug design, including molecular docking and pharmacophore analysis. This study presents a new opportunity for designing potent and selective drugs for Chagas disease.

Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment.

Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs.

Antimicrobial and cell viability measurement of bovine serum albumin capped silver nanoparticles (Ag/BSA) loaded collagen immobilized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) film.

Bacterial infection of orthopedic devices has been a major concern in joint replacement procedures. Therefore, this study is aimed at formulating collagen immobilized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) film loaded with bovine serum albumin capped silver nanoparticles (Ag/BSA NPs) to inhibit bacterial growth while retaining/promoting osteoblast cells viability. The nanoparticles loaded collagen immobilized PHBV film was characterized for its composition by X-ray Photoelectron Spectroscopy and Anodic Stripping Voltammetry. The extent of loading of Ag/BSA NPs on collagen immobilized PHBV film was found to depend on the chemistry of the functionalized PHBV film and the concentration of Ag/BSA NPs solution used for loading nanoparticles. Our results showed that more Ag/BSA NPs were loaded on higher molecular weight collagen immobilized PHEMA-g-PHBV film. Maximum loading of Ag/BSA NPs on collagen immobilized PHBV film was observed when 16ppm solution was used for adsorption studies. Colony forming unit and optical density measurements showed broad antimicrobial activity towards Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa at significantly lower concentration i.e., 0.19 and 0.31µg/disc, compared to gentamicin and sulfamethoxazole trimethoprim while MTT assay showed that released nanoparticles from Ag/BSA NPs loaded collagen immobilized PHBV film has no impact on MCTC3-E1 cells viability.