SARNP,a participant in mRNA splicing and export,negatively regulates E-cadherin expression via interaction with pinin

Triple-negative breast cancer (TNBC) is associated with a high mortality rate, which is related to the insufficient number of appropriate biomarkers and targets. Therefore, there is an urgent need to discover appropriate biomarkers and targets for TNBC. SARNP (Hcc-1 and CIP29) is highly expressed in several cancers. It binds to UAP56, an RNA helicase component of the TREX complex in messenger RNA (mRNA) splicing and export. However, the role of SARNP in mRNA splicing and export and in the progression of breast cancer, especially of TNBC, remains unknown. Therefore, we examined the role of SARNP in mRNA splicing and export and progression of TNBC. We confirmed that SARNP binds to UAP56 and Aly and that SARNP overexpression enhances mRNA splicing, whereas its knockdown suppressed mRNA export. The SARNP overexpression induced the proliferation of MCF7 cells, whereas its knockdown induced E-cadherin expression and downregulated vimentin and N-cadherin expressions in SK-BR-3 and MDA-MB-231 cells. SARNP downregulates E-cadherin expression by interaction with pinin. Mice injected with MDA-MB-231_shSARNP cells exhibited a significant reduction in tumor growth and lung metastasis compared with those injected with MDA-MB-231_shCon cells in vivo. These findings suggested that SARNP is involved in mRNA splicing and export. SARNP maintains mesenchymal phenotype by escaping from inhibitory interaction with pinin leading to the downregulation of E-cadherin expression.     

Bacterial genome mapper: A comparative bacterial genome mapping tool

Recently, next generation sequencing (NGS) technologies have led to a revolutionary increase in sequencing speed and costefficacy. Consequently, a vast number of contigs from many recently sequenced bacterial genomes remain to be accurately mapped and annotated, requiring the development of more convenient bioinformatics programs. In this paper, we present a newly developed web-based bioinformatics program, Bacterial Genome Mapper, which is suitable for mapping and annotating contigs that have been assembled from bacterial genome sequence raw data. By constructing a multiple alignment map between target contig sequences and two reference bacterial genome sequences, this program also provides very useful comparative genomics analysis of draft bacterial genomes. AVAILABILITY: The database is available for free at http://mbgm.kribb.re.kr.     

Two cation transporters Ena1 and Nha1 cooperatively modulate ion homeostasis, antifungal drug resistance, and virulence of Cryptococcus neoformans via the HOG pathway

Maintenance of cation homeostasis is essential for survival of all living organisms in their biological niches. It is also important for the survival of human pathogenic fungi in the host, where cation concentrations and pH will vary depending on different anatomical sites. However, the exact role of diverse cation transporters and ion channels in virulence of fungal pathogens remains elusive. In this study we functionally characterized ENA1 and NHA1, encoding a putative Na(+)/ATPase and Na(+)/H(+) antiporter, respectively, in Cryptococcus neoformans, a basidiomycete fungal pathogen which causes fatal meningoencephalitis. Expression of NHA1 and ENA1 is induced in response to salt and osmotic shock mainly in a Hog1-dependent manner. Phenotypic analysis of the ena1Δ, nha1Δ, and ena1Δnha1Δ mutants revealed that Ena1 controls cellular levels of toxic cations, such as Na(+) and Li(+) whereas both Ena1 and Nha1 are important for controlling less toxic K(+) ions. Under alkaline conditions, Ena1 was highly induced and required for growth in the presence of low levels of Na(+) or K(+) salt and Nha1 played a role in survival under K(+) stress. In contrast, Nha1, but not Ena1, was essential for survival at acidic conditions (pH 4.5) under high K(+) stress. In addition, Ena1 and Nha1 were required for maintenance of plasma membrane potential and stability, which appeared to modulate antifungal drug susceptibility. Perturbation of ENA1 and NHA1 enhanced capsule production and melanin synthesis. However, Nha1 was dispensable for virulence of C. neoformans although Ena1 was essential. In conclusion, Ena1 and Nha1 play redundant and discrete roles in cation homeostasis, pH regulation, membrane potential, and virulence in C. neoformans, suggesting that these transporters could be novel antifungal drug targets for treatment of cryptococcosis.     

Cell therapy for skin wound using fibroblast encapsulated poly(ethylene glycol)-poly(L-alanine) thermogel

As a new application of a thermogel, a poly(ethylene glycol)-b-poly(L-alanine) (PEG-L-PA) gel encapsulating fibroblasts was investigated for wound healing. The fibroblasts were encapsulated by the temperature sensitive sol-to-gel transition of the polymer aqueous solution. Under the in vitro three-dimensional (3D) cell culture condition, the PEG-L-PA thermogel was comparable with Matrigel for cell proliferation and was significantly better than Matrigel for collagen types I and III formation. After confirming the excellent 3D microenvironment of the PEG-L-PA thermogel for fibroblasts, in vivo wound healing was investigated by injecting the cell-suspended polymer aqueous solution on incisions of rat skin, where the cell-encapsulated gel was formed in situ. Compared with the phosphate buffered saline treated system and the cell-free PEG-L-PA thermogel, the cell-encapsulated PEG-L-PA thermogel not only accelerated the wound closure but also improved epithelialization and the formation of skin appendages such as keratinocyte layer (epidermis), hair follicles, and sebaceous glands. The results demonstrate the potential of thermogels for cell therapy as an injectable tissue-engineering scaffold.     

Extracellular vesicles shed from gefitinib‐resistant nonsmall cell lung cancer regulate the tumor microenvironment

Epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs), including gefitinib, are the first‐line treatment of choice for nonsmall cell lung cancer patients who harbor activating EGFR mutations, however, acquired resistance to EGFR‐TKIs is inevitable. The main objective of this study was to identify informative protein signatures of extracellular vesicles (EV) derived from gefitinib‐resistant nonsmall cell lung cancer cells using proteomics analysis. Nano‐LC–MS/MS analysis identified with high confidence (false discovery rate < 0.05, fold change ≥2) 664 EV proteins enriched in PC9R cells, which are resistant to gefitinib due to EGFR T790M mutation. Computational analyses suggested components of several signal transduction mechanisms including the AKT (also PKB, protein kinase B)/mTOR (mechanistic target of rapamycin) pathway are overrepresented in EV from PC9R cells. Treatment of recipient cells with EV harvested from PC9R cells increased phosphorylation of signaling molecules, and enhanced proliferation, invasion, and drug resistance to gefitinib‐induced apoptosis. Dose‐ and time‐dependent pharmaceutical inhibition of AKT/mTOR pathway overcame drug resistance of PC9R cells and those of H1975 exhibiting EGFR T790M mutation. Our findings provide new insight into an oncogenic EV protein signature regulating tumor microenvironment, and will aid in the development of novel diagnostic strategies for prediction and assessment of gefitinib resistance.     

Effects of global warming on mosquitoes & mosquito‐borne diseases and the new strategies for mosquito control

Global warming has shortened mosquitoes’ lifecycle period and increased the disease transmission rates by mosquito vectors. We reviewed only three mosquito‐borne diseases: malaria, dengue fever, and the Japanese encephalitis. Billions of people get infected with those diseases and millions of people die every year. Although we struggle to find the most effective way to control mosquitoes using various methods (including pesticides), mosquito‐borne diseases are still among the most serious problems being faced. This paper, therefore, reviews the strategies for controlling mosquitoes. The use of pesticides to control mosquitoes might have more negative effects on humans and environments than benefits. Although the development of genetically modified (GM) mosquitoes raises new hopes for effective mosquito control, it will take longer to assess the risks to humans and environments. Furthermore, there has been concern about the possible adverse effects from the release of GM mosquitoes into the environment. The various mosquito traps may not be as effective at controlling only female mosquito populations. Therefore, new strategies for the control of mosquitoes are vital. The smart mosquito counter device was developed by Korean Centre for Disease Control (KCDC) in 2013. The mosquito pest control office is able to set up the appropriate mosquito control strategies by using quantitative mosquito information. The smart device will bring mosquito control in line with modern smart generation technology and the device will also soon be able to identify different mosquito species. This new strategy will change the methods of mosquito control and will provide beneficial effects toward sustainable nature and human health.     

Benign Solutions and Innovative Sequential Annealing Processes for High Performance Cu2ZnSn(Se,S)4 Photovoltaics

Solution‐based earth‐abundant Cu₂ZnSn(Se,S)₄ (CZTSSe) is proven to be a promising tool for thin‐film photovoltaic fabrication. Combining fully dissolved copper (Cu) and zinc/tin (Zn/Sn) hydrazinium constituents in an ethanolamine (EA) and dimethylsulfoxide (DMSO) solution mixture forms the CZTS precursor. All solutes in the precursor solution are intermixed on the molecular scale with excellent homogeneity. Sequential annealing steps under chalcogen vapor allow for enhanced grain growth while preventing the back contact from forming an excessively thick Mo(S,Se)₂ layer. The resulting devices achieve power conversion efficiencies of 7.5% under 1 sun conditions.     

Demulsification of oil-rich emulsion from enzyme-assisted aqueous extraction of extruded soybean flakes

Extraction of soybean oil from flaked and extruded soybeans using enzyme-assisted aqueous extraction processing (EAEP) is a promising alternative to conventional hexane extraction. The efficiencies of four proteases releasing oil from extruded material were compared. Protex 51FP, Protex 6L and Protex 7L each extracted 90% of the total oil available while Protex 50FP gave similar extraction yield as the control (without enzyme treatment). During EAEP, however, a stable emulsion forms that must be broken in order to recover free soybean oil. The potential of various proteases and phospholipases to destabilize the emulsion was determined. Two enzymes, a phospholipase A2 (LysoMax) and a protease (Protex 51FP) were selected to determine the effect of enzyme concentration on demulsification. Although at a 2% concentration (w/w, enzyme/(cream+free oil)), each enzyme tested was effective in totally destabilizing the cream; the protease released significantly more free oil than did the phospholipase at concentrations less than 2%. At 0.2% concentration, 88 and 48% of free oil were obtained with the protease and phospholipase, respectively. Reducing the pH of the cream also destabilized the cream with maximum demulsification at the isoelectric point of soy proteins. These results provide destabilization strategies for the oil-rich emulsion formed during aqueous extraction processing of extruded flakes and significantly contribute to the development of this environmentally-friendly technology.