Phospholipase C-delta1 rescues intracellular Ca2+ overload in ischemic heart and hypoxic neonatal cardiomyocytes

Ischemia and simulated ischemic conditions cause intracellular Ca2+ overload in the myocardium. The relationship between ischemia injury and Ca2+ overload has not been fully characterized. The aim of the present study was to investigate the expression and characteristics of PLC isozymes in myocardial infarction-induced cardiac remodeling and heart failure. In normal rat heart tissue, PLC-delta1 (about 44 ng/mg of heart tissue) was most abundant isozymes compared to PLC-gamma1 (6.8 ng/mg) and PLC-beta1 (0.4 ng/mg). In ischemic heart and hypoxic neonatal cardiomyocytes, PLC-delta1, but not PLC-beta1 and PLC-gamma1, was selectively degraded, a response that could be inhibited by the calpain inhibitor, calpastatin, and by the caspase inhibitor, zVAD-fmk. Overexpression of the PLC-delta1 in hypoxic neonatal cardiomyocytes rescued intracellular Ca2+ overload by ischemic conditions. In the border zone and scar region of infarcted myocardium, and in hypoxic neonatal cardiomyocytes, the selective degradation of PLC-delta1 by the calcium sensitive proteases may play important roles in intracellular Ca2+ regulations under the ischemic conditions. It is suggested that PLC isozyme-changes may contribute to the alterations in calcium homeostasis in myocardial ischemia.     

Characterization of RyDEN (C19orf66) as an Interferon-Stimulated Cellular Inhibitor against Dengue Virus Replication

Dengue virus (DENV) is one of the most important arthropod-borne pathogens that cause life-threatening diseases in humans. However, no vaccine or specific antiviral is available for dengue. As seen in other RNA viruses, the innate immune system plays a key role in controlling DENV infection and disease outcome. Although the interferon (IFN) response, which is central to host protective immunity, has been reported to limit DENV replication, the molecular details of how DENV infection is modulated by IFN treatment are elusive. In this study, by employing a gain-of-function screen using a type I IFN-treated cell-derived cDNA library, we identified a previously uncharacterized gene, C19orf66, as an IFN-stimulated gene (ISG) that inhibits DENV replication, which we named Repressor of yield of DENV (RyDEN). Overexpression and gene knockdown experiments revealed that expression of RyDEN confers resistance to all serotypes of DENV in human cells. RyDEN expression also limited the replication of hepatitis C virus, Kunjin virus, Chikungunya virus, herpes simplex virus type 1, and human adenovirus. Importantly, RyDEN was considered to be a crucial effector molecule in the IFN-mediated anti-DENV response. When affinity purification-mass spectrometry analysis was performed, RyDEN was revealed to form a complex with cellular mRNA-binding proteins, poly(A)-binding protein cytoplasmic 1 (PABPC1), and La motif-related protein 1 (LARP1). Interestingly, PABPC1 and LARP1 were found to be positive modulators of DENV replication. Since RyDEN influenced intracellular events on DENV replication and, suppression of protein synthesis from DENV-based reporter construct RNA was also observed in RyDEN-expressing cells, our data suggest that RyDEN is likely to interfere with the translation of DENV via interaction with viral RNA and cellular mRNA-binding proteins, resulting in the inhibition of virus replication in infected cells.     

Genome-wide DNA polymorphism and transcriptome analysis of an early-maturing rice mutant

In order to develop a rice population with improved important traits such as flowering time, we developed 2,911 M₂ targeting-induced local lesions in genomes (TILLING) lines by irradiating rice seeds with γ-rays. In all, 15 M₃ lines were obtained from 3 different M₂ lines that exhibited an early-maturing phenotype: these plants matured approximately 25 days faster than wild-type (WT) plants. To identify genome-wide DNA polymorphisms, we performed whole-genome resequencing of both the plant types, i.e., WT and early-maturing TILLING 1 (EMT1), and obtained mapped reads of 118,488,245 bp (99.53 %) and 128,489,860 bp (99.72 %), respectively; Nipponbare was used as the reference genome. We obtained 63,648 and 147,728 single nucleotide polymorphisms (SNPs) and 33,474 and 31,082 insertions and deletions (InDels) for the WT and EMT1, respectively. Interestingly, there was a higher number of SNPs (2.6-fold) and slightly lower number of InDels (0.9-fold) in EMT1 than in WT. The expression of at least 202 structurally altered genes was changed in EMT1, and functional enrichment analysis of these genes revealed that their molecular functions were related to flower development. These results might provide a critical insight into the regulatory pathways of rice flowering.     

Structural characterization and interaction of periostin and bone morphogenetic protein for regulation of collagen cross-linking

Periostin appears to be a unique extracellular protein secreted by fibroblasts that is upregulated following injury to the heart or changes in the environment. Periostin has the ability to associate with other critical extracellular matrix (ECM) regulators such as TGF-β, tenascin, and fibronectin, and is a critical regulator of fibrosis that functions by altering the deposition and attachment of collagen. Periostin is known to be highly expressed in carcinoma cells, but not in normal breast tissues. The protein has a structural similarity to insect fasciclin-1 (Fas 1) and can be induced by transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP)-2. To investigate the molecular interaction of periostin and bone morphogenetic protein, we modeled these three-dimensional structures and their binding sites. We demonstrated direct interaction between periostin and BMP1/2 in vitro using several biochemical and biophysical assays. We found that the structures of the first, second, and fourth Fas1 domains in periostin are similar to that of the fourth Fas 1 domain of TGFBIp. However, the structure of the third Fas 1 domain in periostin is different from those of the first, second, and fourth Fas1 domains, while it is similar to the NMR structure of Fasciclin-like protein from Rhodobacter sphaeroides. These results will useful in further functional analysis of the interaction of periostin and bone morphogenetic protein.     

Jabuticaba‐Inspired Hybrid Carbon Filler/Polymer Electrode for Use in Highly Stretchable Aqueous Li‐Ion Batteries

Stretchable electronics are considered as next‐generation devices; however, to realize stretchable electronics, it is first necessary to develop a deformable energy device. Of the various components in energy devices, the fabrication of stretchable current collectors is crucial because they must be mechanically robust and have high electrical conductivity under deformation. In this study, the authors present a conductive polymer composite composed of Jabuticaba‐like hybrid carbon fillers containing carbon nanotubes and carbon black in a simple solution process. The hybrid carbon/polymer (HCP) composite is found to effectively retain its electrical conductivity, even when under high strain of ≈200%. To understand the behavior of conductive fillers in the polymer matrix when under mechanical strain, the authors investigate the microstructure of the composite using an in situ small‐angle X‐ray scattering analysis. The authors observe that the HCP produces efficient electrical pathways for filler interconnections upon stretching. The authors develop a stretchable aqueous rechargeable lithium‐ion battery (ARLB) that utilizes this HCP composite as a stretchable current collector. The ARLB exhibits excellent rate capability (≈90 mA h g^?1 at a rate of 20 C) and outstanding capacity retention of 93% after 500 cycles. Moreover, the stretchable ARLB is able to efficiently deliver power even when under 100% strain.     

Highly Conductive,Light Weight,Robust, Corrosion‐Resistant,Scalable, All‐Fiber Based Current Collectors for Aqueous Acidic Batteries

Lithium‐ion batteries (LIBs) are integral parts of modern technology, but can raise safety concerns because of their flammable organic electrolytes with low flash points. Aqueous electrolytes can be used in LIBs to overcome the safety issues that come with organic electrolytes while avoiding poor kinetics associated with solid state electrolytes. Despite advances in aqueous electrolytes, current collectors for aqueous battery systems have been neglected. Current collectors used in today's aqueous battery systems are usually metal‐based materials, which are heavy, expensive, bulky, and prone to corrosion after prolonged use. Here, a carbon nanotube (CNT)–cellulose nanofiber (CNF) all‐fiber composite is developed that takes advantage of the high conductivity of CNT while achieving high mechanical strength through the interaction between CNT and CNF. By optimizing the CNT/CNF weight ratio, this all‐fiber current collector can be made very thin while maintaining high conductivity (≈700 S cm^?1) and strength (>60 MPa), making it an ideal replacement for heavy metal current collectors in aqueous battery systems.     

Fine needle aspiration cytology of metastatic olfactory neuroblastoma: a case report

BACKGROUND: Olfactory neuroblastoma (ONB) is an uncommon tumor, presenting as a polypoid mass arising from the upper nasal cavity. This tumor has been seldom diagnosed by direct fine needle aspiration (FNA). CASE: Metastatic ONB was diagnosed by FNA. The patient was a 40-year-old female with a polypoid mass in the nasal cavity and ipsilateral cervical lymphadenopathy. The punch biopsy of the nasal tumor revealed a smudged small round cell neoplasm with neuroendocrine differentiation, consistent with ONB. In FNA smears from the cervical lymph node, there were well-preserved, small, monotonous cells with hyperchromatic nuclei, fibrillary cytoplasm and indistinct cell borders. Also noteworthy were occasional pseudorosettes as well as rare true rosettes. By immunocytochemistry, tumor cells were positive for cytokeratin, chromogranin and synaptophysin. CONCLUSION: ONB, like adrenal neuroblastoma, shows distinctive cytologic features, including a rosette or pseudorosette and fibrillary network. FNA can accurately demonstrate these characteristic findings, and in some cases it may be a better diagnostic modality than incisional biopsy.     

Lipase and its modulator from Pseudomonas sp. strain KFCC 10818: proline-to-glutamine substitution at position 112 induces formation of enzymatically active lipase in the absence of the modulator

A lipase gene, lipK, and a lipase modulator gene, limK, of Pseudomonas sp. strain KFCC 10818 have been cloned, sequenced, and expressed in Escherichia coli. The limK gene is located immediately downstream of the lipK gene. Enzymatically active lipase was produced only in the presence of the limK gene. The effect of the lipase modulator LimK on the expression of active lipase was similar to those of the Pseudomonas subfamily I.1 and I.2 lipase-specific foldases (Lifs). The deduced amino acid sequence of LimK shares low homology (17 to 19%) with the known Pseudomonas Lifs, suggesting that Pseudomonas sp. strain KFCC 10818 is only distantly related to the subfamily I.1 and I.2 Pseudomonas species. Surprisingly, a lipase variant that does not require LimK for its correct folding was isolated in the study to investigate the functional interaction between LipK and LimK. When expressed in the absence of LimK, the P112Q variant of LipK formed an active enzyme and displayed 63% of the activity of wild-type LipK expressed in the presence of LimK. These results suggest that the Pro(112) residue of LipK is involved in a key step of lipase folding. We expect that the novel finding of this study may contribute to future research on efficient expression or refolding of industrially important lipases and on the mechanism of lipase folding.