Glutamate-activated chloride channels: Unique fipronil targets present in insects but not in mammals

Selectivity to insects over mammals is one of the important characteristics for a chemical to become a useful insecticide. Fipronil was found to block cockroach GABA receptors more potently than rat GABA_A receptors. Furthermore, glutamate-activated chloride channels (GluCls), which are present in cockroaches but not in mammals, were very sensitive to the blocking action of fipronil. The IC₅₀s of fipronil block were 30 nM in cockroach GABA receptors and 1600 nM in rat GABA_A receptors. Moreover, GluCls of cockroach neurons had low IC₅₀s for fipronil. Two types of glutamate-induced chloride current were observed: desensitizing and non-desensitizing, with fipronil IC₅₀s of 800 and 10 nM, respectively. We have developed methods to separately record these two types of GluCls. The non-desensitizing and desensitizing currents were selectively inhibited by trypsin and polyvinylpyrrolidone, respectively. In conclusion, in addition to GABA receptors, GluCls play a crucial role in selectivity of fipronil to insects over mammals. GluCls form the basis for development of selective and safe insecticides.     

Alpinia zerumbet potentially elevates high-density lipoprotein cholesterol level in hamsters

In folkloric plant medicines, Alpinia zerumbet (AZ) has been popularly recognized as an exellent hepatoprotector. To search for a good high-density lipoprotein cholesterol (HDL-C) elevating herbal preparation, we examined AZ for its antioxidant and hypolipidaemic bioactivities, especially its HDL-C elevating activity. AZ seeds contain 0.51% essential oils (SO), which are comprised of monoterpenoids, oxygenated monoterpenoids, sesquiterpenoids, oxygenated sesquiterpenoids, aldehydes, acid, and esters. Gas chromatography/mass spectrometry analysis indicated that most of the monoterpenes and sesquiterpenes were recoverable in pentane eluent, whilst the oxygenated monoterpenoids and sesquiterpenoids remained in ether eluent. The high contents of rutin, quercetin, and polyphenolics in ethanolic extract of AZ seeds exhibit moderate antilipoperoxidative but potent DPPH free radical scavenging bioactivities. Conclusively, both seed powder (SP) and SO are effective hypolipidaemics with amazingly potent HDL-C elevating capabilities. On the basis of hepatoprotectivity, SP is a more feasible hypolipidemic agent as well as a promising HDL-C elevating plant medicine.     

Multilocus phylogeography and ecological niche modeling suggest speciation with gene flow between the two Bamboo Partridges

Background: Understanding how species diversify is a long-standing question in biology. The allopatric speciation model is a classic hypothesis to explain the s...     

The ability of <Emphasis Type="Italic">Papaya ringspot virus</Emphasis>strains overcoming the transgenic resistance of papaya conferred by the coat protein gene is not correlated with higher degrees of sequence divergence from the transgene

The coat protein (CP) gene mediated transgenic resistance is found to be the best approach for protecting papaya plants against the destructive disease caused by Papaya ringspot viruses(PRSV). In order to study the variability of PRSV and the potential threat to the CP-transgenic resistance, five virus isolates were collected from transgenic plants of papaya line 16-0-1, which carry the CP gene of the typical mosaic strain of Taiwan PRSV YK, in an approved test field and fourteen from untransformed papaya plants in different areas of Taiwan. The results of biological, serological, and molecular characterization indicated that all isolates are related to PRSV YK. Among them, the isolate 5--19 from the transgenic line and the isolates CS and TD2 from untransformed papaya were able to overcome the YK CP gene-mediated resistance of papaya lines 18--2--4, 17-0-5, and 16-0-1, which provide high degrees of resistance to different geographic PRSV strains of Hawaii (HA), Mexico (MX), and Thailand (TH). These three isolates were also able to cause symptoms on untransformed papaya plants more severe than those induced by YK. In addition to the host reactions, the variability of the collected 19 isolates was also analyzed and compared with YK and other geographic strains by heteroduplex mobility assay (HMA) and sequence analyses. The results of HMA indicated that the CP genes of isolates 5--19 and TD2 are more divergent than those of other isolates when compared with YK. However, sequence analyses of the transgenic-resistance overcoming isolates 5-19, CS, and TD2 revealed that their CP coding regions and the 3 untranslated regions (UTRs) share nucleotide identities of 93.9–96.6% and 94.2–97.9% with those of YK, respectively; whereas the other geographic strains of HA, MX, and TH that could not overcome the transgenic resistance share lower nucleotide identities of 89.8–92.6% and 92.3–95.3% with those of YK, respectively. Our results indicate that the ability for overcoming the transgenic resistance is not solely correlated with higher degrees of sequence divergence from the transgene. The possible mechanism for overcoming the transgenic resistance and the potential threat of these PRSV strains to the application of the transgenic papaya lines carrying PRSV YK CP gene are discussed.     

Maxillary bone epithelial cyst in an adult miniature schnauzer

Maxillary bone epithelial cyst is rare in dogs. A 5-year-old, spayed female miniature schnauzer developed a swelling below the nasal canthus of left eye. Plain radiograph demonstrated a 1.5 cm diameter of radiolucent lesion on the maxillary bone anteroventral to the eye, and contrast dacryocystorhinography confirmed an obstructed nasolarcrimal duct. The swelling showed poor response to antibiotic treatment but responded well to oral prednisolone. Exploratory surgery revealed a cyst-like structure filled with brown serous fluid. Histopathological examination of the removed cyst revealed a double cuboidal epithelial cyst. The dog recovered rapidly after surgery, and the swelling had not recurred for a 36-month follow-up. It is the first case of periorbital bone epithelial cyst reported in an adult miniature schnauzer.     

Sulforaphane potentiates the efficacy of imatinib against chronic leukemia cancer stem cells through enhanced abrogation of Wnt/β-catenin function

Sulforaphane (SFN) has been indicated for the prevention and suppression of tumorigenesis in solid tumors. Herein, we evaluated SFN's effects on imatinib (IM)-resistant leukemia stem cells (LSCs). CD34(+)/CD38(-) and CD34(+)/CD38(+) LSCs were isolated from KU812 cell line flowcytometrically. Isolated LSCs showed high expression of Oct4, CD133, β-catenin, and Sox2 and IM resistance. Differentially, CD34(+)/CD38(-) LSCs demonstrated higher BCR-ABL and β-catenin expression and imatinib (IM) resistance than CD34(+)/CD38(+) counterparts. IM and SFN combined treatment sensitized CD34(+)/CD38(-) LSCs and induced apoptosis, shown by increased caspase 3, PARP, and Bax while decreased Bcl-2 expression. Additionally, the combined treatment reduced BCR-ABL and β-catenin and MDR-1 protein expression. Mechanistically, IM and SFN combined treatment resensitized LSCs by inducing intracellular reactive oxygen species (ROS). Importantly, β-catenin-silenced LSCs exhibited reduced glutathione S-transferase pi 1 (GSTP1) expression and intracellular GSH level, which led to increased sensitivity toward IM and SFN. We demonstrated that IM and SFN combined treatment effectively eliminated CD34(+)/CD38(-) LSCs. Since SFN has been shown well tolerated in both animals and human, this regimen could be considered for clinical trials.     

Investigation of the structural performance of glulam beam connections using self-tapping screws

The characteristic strength properties of structural glulam connections assembled with self-tapping screws were examined following the ASTM testing procedure in the study. Four screw types with various numbers were designated at each connection of the beam–girder structure with different nailing schedules. The results indicated that the maximum load capacity and dissipated energy of a connection fastened with 10-mm self-tapping screws were higher than those with 8-mm screws. And, the screws with both double-threaded sections and fully threaded shanks were higher than those of single-threaded screws. An improvement on the initial stiffness of a connection was found when the number of self-tapping screws increased. The connections assembled with the toe-nailing approach from the beam’s bottom surface provided higher maximum loading capacity, medium initial stiffness, and a larger ductility factor, resulting in higher dissipated energy with less fragile failure. The derived allowable loading values for a beam–girder connection fastened with self-tapping screws using the face-nailing approach were close to the code values for bolted and pinned connections. And, a toe-nailing approach provided higher allowable loads for connections than using a face-nail approach.