Uncovering the novel characteristics of Asian honey bee, Apis cerana, by whole genome sequencing

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Abstract Background The honey bee is an important model system for increasing understanding of molecular and neural mechanisms underlying social behaviors relevant to the agricultural industry and basic science. The western honey bee, Apis mellifera, has served as a model species, and its genome sequence has been published. In contrast, the genome of the Asian honey bee, Apis cerana, has not yet been sequenced. A. cerana has been raised in Asian countries for thousands of years and has brought considerable economic benefits to the apicultural industry. A cerana has divergent biological traits compared to A. mellifera and it has played a key role in maintaining biodiversity in eastern and southern Asia. Here we report the first whole genome sequence of A. cerana. Results Using de novo assembly methods, we produced a 238 Mbp draft of the A. cerana genome and generated 10,651 genes. A.cerana-specific genes were analyzed to better understand the novel characteristics of this honey bee species. Seventy-two percent of the A. cerana-specific genes had more than one GO term, and 1,696 enzymes were categorized into 125 pathways. Genes involved in chemoreception and immunity were carefully identified and compared to those from other sequenced insect models. These included 10 gustatory receptors, 119 odorant receptors, 10 ionotropic receptors, and 160 immune-related genes. Conclusions This first report of the whole genome sequence of A. cerana provides resources for comparative sociogenomics, especially in the field of social insect communication. These important tools will contribute to a better understanding of the complex behaviors and natural biology of the Asian honey bee and to anticipate its future evolutionary trajectory

日韓両言語における外来語の受容に関する対照研究

2021【要旨

Current Insights into Combination Therapies with MAPK Inhibitors and Immune Checkpoint Blockade

The recent development of high-throughput genomics has revolutionized personalized medicine by identifying key pathways and molecular targets controlling tumor progression and survival. Mitogen-activated protein kinase (MAPK) pathways are examples of such targets, and inhibitors against these pathways have shown promising clinical responses in patients with melanoma, non-small-cell lung cancer, colorectal cancer, pancreatic cancer, and thyroid cancer. Although MAPK pathway-targeted therapies have resulted in significant clinical responses in a large proportion of cancer patients, the rate of tumor recurrence is high due to the development of resistance. Conversely, immunotherapies have shown limited clinical responses, but have led to durable tumor regression in patients, and complete responses. Recent evidence indicates that MAPK-targeted therapies may synergize with immune cells, thus providing rationale for the development of combination therapies. Here, we review the current status of ongoing clinical trials investigating MAPK pathway inhibitors, such as BRAF and MAPK/ERK kinase (MEK) inhibitors, in combination with checkpoint inhibitors targeting programmed death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T cell associated antigen-4 (CTLA-4). A better understanding of an individual drug’s mechanism of action, patterns of acquired resistance, and the influence on immune cells will be critical for the development of novel combination therapies

Performance and emission characteristics of a vehicle fueled with enriched biogas and natural gases

This study aimed to investigate the characteristics of exhaust emissions and the fuel economy of a compressed natural gas (CNG) vehicle fueled with biogas and natural gases. A large CNG vehicle currently used as a city bus in Korea was tested on a chassis dynamometer under the European Transient Cycle (ETC) and the National Institute of Environmental Research (NIER) 06 cycles. One CH4-enriched biogas (97.6% CH4) and 5 natural gases with different CH4 contents (81.6-94.0% CH4) were used as test fuels. Total hydrocarbons (THC), CO, NOx and CO2 emissions in the NIER 06 cycle were higher than those in the ETC cycle for all tested fuels, while the fuel economy in the NIER 06 cycle was 43.7-51.5% lower than that in the ETC cycle. Total VOC emissions increased with increasing CH4 content in the fuel, with toluene being the highest proportion of the BTEX emissions in both the ETC cycle (72-80%) and the NIER 06 cycle (73-78%). Emissions of elemental/organic carbon exhibited a similar trend to that of nanoparticle emissions. Total organic carbon was mainly comprised of organic compounds at 97-99% (ETC cycle) and 95-99% (NIER 06 cycle). Polycyclic aromatic hydrocarbon emissions in the NIER 06 cycle were 133.3-577.8% higher than in the ETC cycle because of incomplete combustion and an increase in unburned fuel in the NIER 06 cycle, which is a low-speed driving mode. Nanoparticle number concentrations were lowest for M91 among the 6 tested fuels; the total number of particles in the NIER 06 cycle was 33.2-123.8% higher than in the ETC cycle.close7

Evaluation of Chloride-Ion Diffusion Characteristics of Wave Power Marine Concrete Structures

Wave power marine concrete structures generate electrical energy using waves. They are exposed to a multi-deterioration environment because of air and hydrostatic pressure and chloride attack. In this study, the effect of air pressure repeatedly generated by water level change of wave power marine concrete structures on the chloride-ion diffusion of marine concrete was analyzed. The chloride-ion diffusion of wave power marine concrete structures was evaluated. The results show that the air chamber and bypass room, which were subjected to repetitive air pressures caused by water level changes, showed a higher water-soluble chloride-ion content compared to the generator room and docking facility, which were subjected to atmospheric pressure. Field exposure tests and indoor chloride attack tests were performed using fabricated specimens to analyze the effect of pressure on chloride-ion penetration. It was confirmed that Portland blast furnace slag had a greater inhibitory effect on chloride-ion penetration than ordinary Portland cement. The concrete specimens subjected to pressure showed increased capillary pores and micro-cracks. We devised an equation for calculating the diffusion coefficient based on measured data and estimating the diffusion coefficient for the location receiving repeated air pressure by using the diffusion coefficient of the location receiving general atmospheric pressure

Microfluidic Cell Stretching for Highly Effective Gene Delivery into Hard-to-Transfect Primary Cells

Cell therapy and cellular engineering begin with internalizing synthetic biomolecules and functional nanomaterials into primary cells. Conventionally, electroporation, lipofection, or viral transduction has been used; however, these are limited by their cytotoxicity, low scalability, cost, and/or preparation complexity, especially in primary cells. Thus, a universal intracellular delivery method that outperforms the existing methods must be established. Here, we present a versatile intracellular delivery platform that leverages intrinsic inertial flow developed in a T-junction microchannel with a cavity. The elongational recirculating flows exerted in the channel substantially stretch the cells, creating discontinuities on cell membranes, thereby enabling highly effective internalization of nanomaterials, such as plasmid DNA (7.9 kbp), mRNA, siRNA, quantum dots, and large nanoparticles (300 nm), into different cell types, including hard-to-transfect primary stem and immune cells. We identified that the internalization mechanism of external cargos during the cell elongation-restoration process is achieved by both passive diffusion and convection-based rapid solution exchange across the cell membrane. Using fluidic cell mechanoporation, we demonstrated a transfection yield superior to that of other state-of-the-art microfluidic platforms as well as current benchtop techniques, including lipofectamine and electroporation. In summary, the intracellular delivery platform developed in the present study enables a high delivery efficiency (up to 98%), easy operation (single-step), low material cost (<$1), high scalability (1 x 10(6) cells/min), minimal cell perturbation (up to 90%), and cell type/cargo insensitive delivery, providing a practical and robust approach anticipated to critically impact cell-based research.N

Preclinical Evaluation of hnRNPA2B1 Antibody in Human Triple-Negative Breast Cancer MDA-MB-231 Cells via PET Imaging

Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Because TNBC lacks the expression of commonly targeted receptors, it is challenging to develop a new imaging agent for this cancer subtype. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA–protein complexes that have been linked to tumor development and progression. Considering the high expression of hnRNPA2B1, an hnRNP subtype, in TNBC MDA-MB-231 cells, this study aimed to develop a novel hnRNPA2B1 antibody-based nuclear imaging agent. The hnRNPA2B1-specific antibody was radiolabeled with 64Cu and evaluated in vitro and in vivo. The trans-cyclooctene (TCO) was functionalized on the antibody to obtain hnRNP-PEG4-TCO and reactive tetrazine (Tz) on the ultrastable bifunctional chelator PCB-TE2A-alkyne to yield PCB-TE2A-Tz for the inverse electron demand Diels–Alder reaction. The 64Cu-radiolabeled antibody was administered and imaged at 1–18 h time points for conventional imaging. Alternatively, the unlabeled antibody conjugate was administered, and 48 h later radiolabeled 64Cu-PCB-TE2A-Tz was administered to the same mice for the pretargeting strategy and imaged at the same time intervals for direct comparison. The tumor was successfully visualized in both strategies, and comparatively, pretargeting showed superior results. The 64Cu-PCB-TE2A-Tz was successfully clicked at the tumor site with hnRNP-PEG4-TCO and the non-clicked were concurrently eliminated. This led to increase the tumor uptake with extremely high tumor-to-background ratio manifested by positron emission tomography (PET) imaging and biodistribution studies

Gadolinium Complex of ¹²⁵I/¹²⁷I‑RGD-DOTA Conjugate as a Tumor-Targeting SPECT/MR Bimodal Imaging Probe

The work describes the synthesis and in vivo application of [Gd­(L)­(H₂O)]·<i>x</i>H₂O, where L is a (¹²⁵I/¹²⁷I-RGD)- DOTA conjugate, as a tumor-targeting SPECT/MR bimodal imaging probe. Here, (¹²⁵I/¹²⁷I-RGD)-DOTA signifies a “cocktail mixture” of radioisotopic (<b>1a</b>, L = ¹²⁵I-RGD-DOTA) and natural (<b>1b</b>, L = ¹²⁷I-RGD-DOTA) Gd complexes. The two complexes are chemically equivalent as revealed by HPLC, and their cocktail mixture exhibits the integrin-specific tumor enhancement, demonstrating that they constitute essentially a single bimodal imaging probe. Employment of a cocktail mixture thus proves to be a sole and practical approach to overcome the sensitivity difference problem between MRI and SPECT