Role of CARD9 in Cell- and Organ-Specific Immune Responses in Various Infections.

The caspase recruitment domain-containing protein 9 (CARD9) is an intracellular adaptor protein that is abundantly expressed in cells of the myeloid lineage, such as neutrophils, macrophages, and dendritic cells. CARD9 plays a critical role in host immunity against infections caused by fungi, bacteria, and viruses. A CARD9 deficiency impairs the production of inflammatory cytokines and chemokines as well as migration and infiltration, thereby increasing susceptibility to infections. However, CARD9 signaling varies depending on the pathogen causing the infection. Furthermore, different studies have reported altered CARD9-mediated signaling even with the same pathogen. Therefore, this review focuses on and elucidates the current literature on varied CARD9 signaling in response to various infectious stimuli in humans and experimental mice models.

Taurine Chloramine-Mediated Nrf2 Activation and HO-1 Induction Confer Protective Effects in Astrocytes.

Taurine is ubiquitously distributed in mammalian tissues, with the highest levels in the brain, heart, and leukocytes. Taurine reacts with hypochlorous acid (HOCl) to produce taurine chloramine (Tau-Cl) via the myeloperoxidase (MPO) system. In this study, we elucidated the antioxidative and protective effects of Tau-Cl in astrocytes. Tau-Cl increased the expression and nuclear translocation of nuclear factor E2-related factor (Nrf2) and the expression of Nrf2-regulated antioxidant genes, including heme oxygenase 1 (HO-1). Nrf2 activity is negatively regulated by Kelch-like ECH-associated protein 1 (Keap1). Tau-Cl decreased the level of the reduced thiol groups of Keap1, resulting in the disruption of the Keap1-Nrf2 complex. Consequently, Tau-Cl rescued the H2O2-induced cell death by enhancing HO-1 expression and suppressing reactive oxygen species. In conclusion, Tau-Cl confers protective effects in astrocytes by disrupting the Keap1-Nrf2 complex, thereby promoting Nrf2 translocation to the nucleus, wherein it binds to the antioxidant response element (ARE) and accelerates the transcription of antioxidant genes. Therefore, in astrocytes, the activation of the Keap1-Nrf2-ARE pathway by Tau-Cl may increase antioxidants and anti-inflammatory mediators as well as other cytoprotective proteins, conferring protection against brain infection and injury.

Identification of a novel plant RNA virus species of the genus Amalgavirus in the family Amalgaviridae from chia (Salvia hispanica).

BACKGROUND: Chia (Salvia hispanica) is a flowering plant in the family Lamiaceae, which produces seeds that are a rich source of various nutritional compounds. OBJECTIVE: To identify a novel RNA virus potentially associated with chia. METHODS: Transcriptome data obtained from developing chia seeds were assembled into contigs. Sequence contigs containing an open reading frame (ORF) that showed amino acid identities with a viral RNA-dependent RNA polymerase (RdRp) were identified and analyzed. RESULTS: A genomic sequence of a novel plant RNA virus named Salvia hispanica RNA virus 1 (ShRV1) was identified in a chia seed transcriptome dataset. The ShRV1 genome sequence has two ORFs that showed high sequence identities with ORFs of known members of the genus Amalgavirus in the family Amalgaviridae. Amalgaviridae is a family of positive-sense double-stranded non-segmented RNA viruses that infect plants, fungi, and animals. The ShRV1 genome encodes two proteins: a putative replication factory matrix-like protein from ORF1 and an RdRp from the fused ORF of ORF1 and ORF2 by a + 1 programmed ribosomal frameshifting (PRF) mechanism. A conserved + 1 PRF motif sequence UUU_CGU was found at the ORF1/ORF2 boundary. A comparison of 31 amalgavirus ORF1 + 2 fusion proteins revealed that only three positions were repeatedly used as a + 1 PRF site during amalgavirus evolution. CONCLUSION: ShRV1 is a novel virus found to be associated with chia and may be useful for studying the molecular features of amalgaviruses.

Loss of conserved ubiquitylation sites in conserved proteins during human evolution.

Ubiquitylation of lysine residues in proteins serves a pivotal role in the efficient removal of misfolded or unused proteins and in the control of various regulatory pathways by monitoring protein activity that may lead to protein degradation. The loss of ubiquitylated lysines may affect the ubiquitin­mediated regulatory network and result in the emergence of novel phenotypes. The present study analyzed mouse ubiquitylation data and orthologous proteins from 62 mammals to identify 193 conserved ubiquitylation sites from 169 proteins that were lost in the Euarchonta lineage leading to humans. A total of 8 proteins, including betaine homocysteine S­methyltransferase, clin and CBS domain divalent metal cation transport mediator 3, ribosome­binding protein 1 and solute carrier family 37 member 4, lost 1 conserved lysine residue, which was ubiquitylated in the mouse ortholog, following the human­chimpanzee divergence. A total of 17 of the lost ubiquitylated lysines are also known to be modified by acetylation and/or succinylation in mice. In 8 cases, a novel lysine evolved at positions flanking the lost conserved lysine residues, potentially as a method of compensation. We hypothesize that the loss of ubiquitylation sites during evolution may lead to the development of advantageous phenotypes, which are then fixed by selection. The ancestral ubiquitylation sites identified in the present study may be a useful resource for investigating the association between loss of ubiquitylation sites and the emergence of novel phenotypes during evolution towards modern humans.

Metabolic burden measured by (18)f-fluorodeoxyglucose positron emission tomography/computed tomography is a prognostic factor in patients with small cell lung cancer.

PURPOSE: Evidence regarding the usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in predicting the prognosis of non-small cell lung cancer is increasing. However, data on small cell lung cancer (SCLC) are scarce. The aim of this study was to evaluate the prognostic value of metabolic parameters measured using (18)F-FDG PET/CT in patients with SCLC. MATERIALS AND METHODS: We conducted a retrospective review of 114 patients with pathologically proven SCLC (26 cases of limited disease and 88 cases of extensive disease) who underwent pretreatment (18)F-FDG PET/CT. The maximal SUV (SUVmax) was used quantitatively for determination of FDG PET activity. The SUVmax of the primary tumor (primary SUVmax), the sum of SUVmax values of malignant lesions (SUVsum), and the mean SUVmax of malignant lesions were calculated. RESULTS: The patient population was subdivided using a median SUVsum value of 24.6. High SUVsum showed a significant association with known factors for poor prognosis, including higher neuron-specific enolase (p=0.010), CYFRA 21-1 (p=0.014), and extensive disease status (p=0.007). Patients with high SUVsum had significantly shorter median overall survival (6.6 months vs. 13.0 months, p<0.001) and progression-free survival (5.2 months vs. 8.0 months, p<0.001) than patients with low SUVsum. Results of multivariate analysis showed that SUVsum, chemotherapy cycles, and the response to first-line treatment were significant prognostic factors of survival. In contrast, mean SUVmax and primary SUVmax were not significant predictors of survival. CONCLUSION: In this study, metabolic burden represented by SUVsum from pretreatment (18)F-FDG PET/CT was an independent prognostic factor in patients with SCLC.

Fabrication of electrospun biocomposites comprising polycaprolactone/fucoidan for tissue regeneration.

In this study, we designed a new biocomposite comprising electrospun polycaprolactone (PCL)/fucoidan, in which the fucoidan has various beneficial biological functions, including anticoagulant, antiviral, and immunomodulatory activity. To obtain the composite scaffolds, a mixture of PCL and fucoidan was electrospun using various compositions (1, 2, 3, and 10 wt.%) of fucoidan powders. The resultant electrospun composites exhibited improved tensile modulus and strength for limited weight fractions (<10 wt.%) of fucoidan when compared with the pure PCL fiber mats. In addition, the biocomposites showed dramatic hydrophilic properties at >3 wt.% of fucoidan in the PCL/fucoidan. The biocompatibility of the electrospun mats was examined in vitro using osteoblast-like cells (MG63). Total protein content, alkaline phosphatase activity, and calcium mineralization were assessed. Scanning electron microscopic images showed that the cells were distributed more widely and were agglomerated on PCL/fucoidan mats compared with pure PCL mats. In addition, total protein content, alkaline phosphatase activity, and calcium mineralization were higher with PCL/fucoidan mats than with pure PCL mats. These observations suggest that fucoidan-supplemented biocomposites would make excellent materials for tissue-engineering applications.

Molecular-level engineering of protein physical hydrogels for predictive sol-gel phase behavior.

Predictable tuning of bulk mechanics from the molecular level remains elusive in many physical hydrogel systems because of the reliance on nonspecific and nonstoichiometric chain interactions for network formation. We describe a mixing-induced two-component hydrogel (MITCH) system, in which network assembly is driven by specific and stoichiometric peptide-peptide binding interactions. By integrating protein science methodologies with a simple polymer physics model, we manipulate the polypeptide binding interactions and demonstrate the direct ability to predict the resulting effects on network cross-linking density, sol-gel phase behavior, and gel mechanics.

Nonpolymeric thermosensitive benzenetricarboxamides.

A new class of nonpolymeric thermosensitive materials based on the benzene-1,3,5-tricarboxamide (BTC) structural platform are described. We observed that the benzocrown ether-substituted BTC derivatives undergo an unusual temperature-dependent reversible solubility change in aqueous solution. Thus, a clear nonfluorescent solution of BTC derivatives becomes turbid and generates fluorescent aggregates above the LCST temperature. The aggregates disappear, and a clear solution is reformed when the solution is cooled to 20 °C. It is believed that the LCST behavior of BTC derivatives results from the removal of water molecules from crown ether moieties at elevated temperature. Thus, BTC derivatives exist in fully hydrated forms below the LCST. Heating the BTC derivatives solutions causes the expulsion of water and induces the formation of aggregates. At room temperature, the removal of water from BTC derivatives occurs slowly and leads to the formation of long nanofibers.

Two-component protein-engineered physical hydrogels for cell encapsulation.

Current protocols to encapsulate cells within physical hydrogels require substantial changes in environmental conditions (pH, temperature, or ionic strength) to initiate gelation. These conditions can be detrimental to cells and are often difficult to reproduce, therefore complicating their use in clinical settings. We report the development of a two-component, molecular-recognition gelation strategy that enables cell encapsulation without environmental triggers. Instead, the two components, which contain multiple repeats of WW and proline-rich peptide domains, undergo a sol-gel phase transition upon simple mixing and hetero-assembly of the peptide domains. We term these materials mixing-induced, two-component hydrogels. Our results demonstrate use of the WW and proline-rich domains in protein-engineered materials and expand the library of peptides successfully designed into engineered proteins. Because both of these association domains are normally found intracellularly, their molecular recognition is not disrupted by the presence of additional biomolecules in the extracellular milieu, thereby enabling reproducible encapsulation of multiple cell types, including PC-12 neuronal-like cells, human umbilical vein endothelial cells, and murine adult neural stem cells. Precise variations in the molecular-level design of the two components including (i) the frequency of repeated association domains per chain and (ii) the association energy between domains enable tailoring of the hydrogel viscoelasticity to achieve plateau shear moduli ranging from approximately 9 to 50 Pa. Because of the transient physical crosslinks that form between association domains, these hydrogels are shear-thinning, injectable, and self-healing. Neural stem cells encapsulated in the hydrogels form stable three-dimensional cultures that continue to self-renew, differentiate, and sprout extended neurites.

Surface functionalization of a poly(vinylidene fluoride): effect on the adhesive and piezoelectric properties.

We studied the effect of the surface functionalization and crystalline phase change of poly(vinylidene fluoride) (PVDF) films on their adhesion and piezoelectric properties. The surface modification of PVDF was carried out with ion beam and/or plasma treatment. These surface modifications were found to alter the interfacial strength between PVDF and metal electrodes and the crystal structure of the piezoelectric PVDF film. A remarkable improvement was found in the interfacial adhesion of the films with thermally deposited metal electrodes, but some piezoelectricity of PVDF film was lost due to the changes in the crystal phase. The proper treatment condition for enhancing the adhesion and retaining piezoelectric structure was suggested.

Vancomycin-induced morphological transformation of self-assembled amphiphilic diacetylene supramolecules.

Reversible ribbon-sphere microstructural transformation of dipeptide-containing diacetylene supramolecules was observed by specific ligand-receptor interactions.

A polydiacetylene-based fluorescent sensor chip.

Self-assembled diacetylene vesicles were spotted and immobilized on aldehyde-modified glass substrates using conventional microarray technology. Irradiation of the immobilized diacetylenes allowed generation of nonfluorescent "blue-phase" polydiacetylene (PDA) arrays. Specific interaction of the PDA vesicle arrays with carbohydrates or poly(acrylic acid) solutions afforded fluorescent profiles.