An Imported Case of Echinococcosis of the Liver in a Korean Who Traveled to Western and Central Europe

Echinococcus granulosus, an intestinal tapeworm of dogs and other canids, infects humans in its larval stage and causes human echinococcosis or hydatid disease. In the Republic of Korea, 31 parasite-proven human echinococcosis cases have been reported, most of which were imported from the Middle East. We recently examined a 61-year-old Korean man who had a large cystic mass in his liver. ELISA was negative for tissue parasitic infections, including echinococcosis, cysticercosis, paragonimiasis, and sparganosis. The patient underwent surgery to remove the cyst, and the resected cyst was processed histopathologically for microscopic examinations. In sectioned cyst tissue, necrotizing protoscolices with disintegrated hooklets of E. granulosus were found. In some areas, only freed, fragmented hooklets were detected. The patient had traveled to western and central Europe in 1996, and had no other history of overseas travel. We report our patient as a hepatic echinococcosis case which was probably imported from Europe.     

S100a9 Knockdown Decreases the Memory Impairment and the Neuropathology in Tg2576 Mice,AD Animal Model

Inflammation, insoluble protein deposition and neuronal cell loss are important features in the Alzheimer''s disease (AD) brain. To investigate the regulatory genes responsible for the neuropathology in AD, we performed microarray analysis with APP_V717I-CT100 transgenic mice, an animal model of AD, and isolated the S100a9 gene, which encodes an inflammation-associated calcium binding protein. In another AD animal model, Tg2576 mouse brain, and in human AD brain, induction of S100a9 was confirmed. The endogenous expression of S100a9 was induced by treatment with Aβ or CT peptides in a microglia cell line, BV2 cells. In these cells, silencing study of S100a9 showed that the induction of S100a9 increased the intracellular calcium level and up-regulated the inflammatory cytokines (IL-1β and TNFα) and iNOS. S100a9 lentiviral short hairpin RNA (sh-S100a9) was injected into the hippocampus region of the brains of 13-month-old Tg2576 mice. At two months after injection, we found that knockdown of S100a9 expression had improved the cognition decline of Tg2576 mice in the water maze task, and had reduced amyloid plaque burden. These results suggest that S100a9 induced by Aβ or CT contributes to cause inflammation, which then affects the neuropathology including amyloid plaques burden and impairs cognitive function. Thus, the inhibition of S100a9 is a possible target for AD therapy.     

Synthesis and biological evaluation of 3-substituted-benzofuran-2-carboxylic esters as a novel class of ischemic cell death inhibitors

A series of 3-substituted-benzofuran-2-carboxylic esters was synthesized and evaluated for biological activity as ischemic cell death inhibitors in H9c2 cells and rat primary cardiac myocytes under conditions of oxygen and glucose deprivation. The introduction of a sulfur atom at the three-position substituent of the benzofuran ring markedly improved ischemic cell death inhibitory potency. In particular, 3-[2-(4-nitro-phenylsulfanyl)-acetylamino]-benzofuran-2-carboxylic acid ester (10) (EC(50)=0.532 μM, cell death=6.18%) and 4-chloro-3-[3-(pyridin-2-ylsulfanyl)-propionylamino]-benzofuran-2-carboxylic ester (18) (EC(50)=0.557 μM, cell death=7.02%) were shown to be the most potent in this series of benzofuran analogs.     

Catalytic Domain of AfsKav Modulates Both Secondary Metabolism and Morphologic Differentiation in Streptomyces avermitilis ATCC 31272

Genetic characterization of afsK-av (SAV3816) in Streptomyces avermitilis ATCC 31272 was performed to evaluate the role(s) of this eukaryotic-type serine–threonine protein kinase (STPK) in the regulation of morphologic differentiation and secondary metabolism. The afsK-av::neo mutant (SJW4001) was defective in sporulation, melanogenesis, and avermectin production. These phenotypic defects were complemented by introduction of either the intact afsK-av or the 900-nt catalytic domain region. The catalytic domain restored sporulation and melanogenesis to SJW4001 whereas it partially recovered avermectin production. This study reveals that AfsKav is a pleiotropic regulator and demonstrates in vivo that the C-region of AfsKav is not essential for its regulatory role in S. avermitilis differentiations.     

Crystal structure of agmatinase reveals structural conservation and inhibition mechanism of the ureohydrolase superfamily

Agmatine is the product of arginine decarboxylation and can be hydrolyzed by agmatinase to putrescine, the precursor for biosynthesis of higher polyamines, spermidine, and spermine. Besides being an intermediate in polyamine metabolism, recent findings indicate that agmatine may play important regulatory roles in mammals. Agmatinase is a binuclear manganese metalloenzyme and belongs to the ureohydrolase superfamily that includes arginase, formiminoglutamase, and proclavaminate amidinohydrolase. Compared with a wealth of structural information available for arginases, no three-dimensional structure of agmatinase has been reported. Agmatinase from Deinococcus radiodurans, a 304-residue protein, shows approximately 33% of sequence identity to human mitochondrial agmatinase. Here we report the crystal structure of D. radiodurans agmatinase in Mn(2+)-free, Mn(2+)-bound, and Mn(2+)-inhibitor-bound forms, representing the first structure of agmatinase. It reveals the conservation as well as variation in folding, oligomerization, and the active site of the ureohydrolase superfamily. D. radiodurans agmatinase exists as a compact homohexamer of 32 symmetry. Its binuclear manganese cluster is highly similar but not identical to the clusters of arginase and proclavaminate amidinohydrolase. The structure of the inhibited complex reveals that inhibition by 1,6-diaminohexane arises from the displacement of the metal-bridging water.     

Establishment of a two-dimensional electrophoresis map for Neospora caninum tachyzoites by proteomics

Expressed proteins and antigens from Neospora caninum tachyzoites were studied by two-dimensional gel electrophoresis and immunoblot analysis combined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Thirty-one spots corresponding to 20 different proteins were identified from N. caninum tachyzoites by peptide mass fingerprinting. Six proteins were identified from a N. caninum database (NTPase, 14-3-3 protein homologue, NcMIC1, NCDG1, NcGRA1 and NcGRA2), and 11 proteins were identified in closely related species using the T. gondii database (HSP70, HSP60, pyruvate kinase, tubulin alpha- and beta-chain, putative protein disulfide isomerase, enolase, actin, fructose-1,6-bisphosphatase, lactate dehydrogenase and glyceradehyde-3-phosphate dehydrogenase). One hundred and two antigen spots were observed using pH 4-7 IPG strips on immunoblot profiles. Among them, 17 spots corresponding to 11 antigenic proteins were identified from a N. caninum protein map. This study involved the construction of in-depth protein maps for N. caninum tachyzoites, which will be of value for studies of its pathogenesis, drug and vaccine development, and phylogenetic studies.     

Insect inventories in a mango‐based agroforestry area in Bangladesh: foraging behavior and performance of pollinators on fruit set

Insect species inventories along with pest prevalence, foraging behavior of pollinators and their effect on fruit set of mango were studied in a mango‐based agroforestry area in Bangladesh during January to June 2013. Of 1751 collected insects, 11 species in five orders and nine families were pests, 13 species in six orders and eight families were predators and eight species belonging to three orders and seven families were found as pollinators. The pests exerted significantly higher abundance but lower diversity than pollinator, predator and other insects. The pollinator richness was found to be lowest but showed higher as well as similar diversity to other category insects. Three pest species prevailed throughout the season and hoppers showed significant abundance. Among the predators, ants were most abundant. Sulphur butterfly and syrphid fly revealed statistically identical and higher abundance than other pollinators. During the flowering season, pests were dominant and the abundance of insects was observed to peak at 11.00 h. The pollinators differed in their landing duration on flowers and their activity led to higher levels of fruit set. This study provides baseline information on insect abundance in an agroforestry system, which stresses the importance of conservation of beneficial insects.     

Molecular Targets for the Testing of COVID‐19

The pandemic outbreaks of coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), spread all over the world in a short period of time. Efficient identification of the infection by SARS‐CoV‐2 has been one of the most important tasks to facilitate all the following counter measurements in dealing with the infectious disease. In Taiwan, a COVID‐19 Open Science Platform adheres to the spirit of open science: sharing sources, data, and methods to promote progress in academic research while corroborating findings from various disciplines has established in mid‐February 2020, for collaborative research in support of the development of detection methods, therapeutics, and a vaccine for COVID‐19. Research priorities include infection control, epidemiology, clinical characterization and management, detection methods (including viral RNA detection, viral antigen detection, and serum antibody detection), therapeutics (neutralizing antibody and small molecule drugs), vaccines, and SARS‐CoV‐2 pathogenesis. In addition, research on social ethics and the law are included to take full account of the impact of the COVID‐19 virus.     

Ethanol inhibits Kv7.2/7.3 channel open probability by reducing the PI(4,5)P2 sensitivity of Kv7.2 subunit

Ethanol often causes critical health problems by altering the neuro-nal activities of the central and peripheral nerve systems. One of the cellular targets of ethanol is the plasma membrane proteins including ion channels and receptors. Recently, we reported that ethanol elevates membrane excitability in sympathetic neurons by inhibiting Kv7.2/7.3 channels in a cell type-specific manner. Even though our studies revealed that the inhibitory effects of ethanol on the Kv7.2/7.3 channel was diminished by the increase of plasma membrane phosphatidylinositol 4,5-bisphosphate (PI (4,5)P₂), the molecular mechanism of ethanol on Kv7.2/7.3 channel inhibition remains unclear. By investigating the kinetics of Kv7.2/7.3 current in high K⁺ solution, we found that ethanol inhibited Kv7.2/7.3 channels through a mechanism distinct from that of tetraethylammonium (TEA) which enters into the pore and blocks the gate of the channels. Using a non-stationary noise analysis (NSNA), we demonstrated that the inhibitory effect of ethanol is the result of reduction of open probability (P_O) of the Kv7.2/7.3 channel, but not of a single channel current (i) or channel number (N). Finally, ethanol selectively facilitated the kinetics of Kv7.2 current suppression by voltage-sensing phosphatase (VSP)-induced PI(4,5)P₂ depletion, while it slowed down Kv7.2 current recovery from the VSP-induced inhibition. Together our results suggest that ethanol regulates neuronal activity through the reduction of open probability and PI(4,5)P₂ sensitivity of Kv7.2/7.3 channels.     

Genetic diversity and structure of the endangered species Megaleranthis saniculifolia in Korea as revealed by allozyme and ISSR markers

The genetic diversity and structure of 12 populations of Megaleranthis saniculifolia, a rare endemic Korean plant, were analyzed using 14 allozyme loci coding 10 enzymes and 78 ISSR loci using seven primers. The genetic diversity of M. saniculifolia at the species level was similar to that observed in out-crossing and long-lived perennials, while at the population level, it was significantly low. The high F _IS value of many populations as well as homozygote excess occurred relatively evenly in many populations in relation to the Hardy-Weinberg expectation, suggesting that inbreeding was occurring within the M. saniculifolia populations. The degree of genetic differentiation based on the two markers was high, and there was no correlation between geographic and genetic distance. Bayesian cluster analysis did not reveal any remarkable geographic trends. Positive correlations were observed between genetic diversity (H _e and h) and population size. Therefore, low genetic diversity within the population and high population differentiation of M. saniculifolia were closely related to the influence of genetic drift, particularly in highly isolated populations. In addition, the fixation of the main alleles at several loci in the opposite direction provided good evidence for genetic drift. The genetic diversity of M. saniculifolia could be compromised if the distribution area or the size of the population were further reduced. In particular, the isolated populations that are fragmented within an area could be at high risk of extinction due to accelerated inbreeding or genetic drift. Considering this, a close monitoring of the population size and of the changes in the genetic structure must be performed. Some practical measures for genetic conservation are also proposed.