Absolute Stereochemistry of TXIB, a Bioactive Plasticizer That Inhibits Oviposition of the Peach Fruit Moth, Carposina sasakii (Lepidoptera: Carposinidae).

TXIB (2,2,4-trimethyl-1,3-pentanediol diisobutyrate), a common plasticizer, inhibits the peach fruit moth, Carposina sasakii from ovipositing on young apple fruits. Using an insect assay and gas chromatography with an electroantennographic detector (GC-EAD) analysis, the stereochemistry of the bioactive compound was identified to be 3R, whereas (3S)-TXIB showed no activity. The inactive enantiomer did not inhibit the activity of commercially available TXIB, which was a racemic mixture. When the female moth was placed on the TXIB-treated fruits in the oviposition assay, she repeated grooming antennae. The reason why the moth detects this artificial compound is unknown, although the stereochemical structure of TXIB could have given an abnormality to the moth's antennae.

Synthesis and activity of 3-oxo-α-ionone analogs as male attractants for the solanaceous fruit fly, Bactrocera latifrons (Diptera: Tephritidae).

A series of 3-oxygenated α-ionone analogs have been developed as highly specific male lures for the solanaceous fruit fly Bactrocera latifrons, a pest of solanaceous fruits. We compared the attractant and phagostimulant activities of analogs with or without (i) unsaturations at the 4,5- and/or 7,8-positions and (ii) oxygen moieties at the 3- and/or 9-positions of the ionone molecule. Since naturally occurring vomifoliol (V2) was found to induce a highly potent phagostimulant activity in B. latifrons males, related analogs including dehydrovomifoliol (V1), 6-hydroxy-α-ionone (U1), and 6-hydroxy-α-ionol (U2) were synthesized to evaluate their attractant and phagostimulant activities. Synthetic V1, V2, U1, and U2 exhibited low attractant activity, but their phagostimulant activity was relatively high. Optical isomers of 3-oxo-7,8-dihydro-α-ionone (P3) and V1 were prepared to examine the stereochemical specificity of attractants. (+)-(6R)-P3 and (+)-(6S)-V1 exhibited the corresponding activities, while their respective antipodal enantiomers were found entirely inactive.

Predominant accumulation of a 3-hydroxy-γ-decalactone in the male rectal gland complex of the Japanese orange fly, Bactrocera tsuneonis.

The Japanese orange fly, Bactrocera tsuneonis, infests various citrus crops. While male pheromone components accumulated in the rectal glands are well characterized for Bactrocera, but information regarding the chemical factors involved in the life cycles of B. tsuneonis remains scarce. Herein, several volatile chemicals including a γ-decalactone, (3R,4R)-3-hydroxy-4-decanolide [(3R,4R)-HD], were identified as major components, along with acetamide and spiroketals as minor components in the rectal gland complexes of male B. tsuneonis flies. The lactone (3R,4R)-HD was also identified in female rectal gland complexes. The amount of this compound in mature males was significantly higher than those observed in females and immature males. The lactone (3R,4R)-HD was detected in flies fed with sucrose only, indicating that this lactone is not derived from dietary sources during adulthood, but biosynthesized in vivo. The predominant accumulation of (3R,4R)-HD in mature males also suggests a possible role in reproductive behavior.

Playground equipment-related head injuries requiring hospitalization in children.

BACKGROUND: The aim of this study was to investigate the circumstances of playground equipment-related head injuries in children and consider preventive measures based on the associated characteristics. METHODS: The survey period was from February 1988 to January 2017. The study participants were children <15 years of age who had been hospitalized for playground equipment-related head injury. The following factors were investigated retrospectively: age; sex; fall height; material of the surface under the equipment; mechanism and diagnosis of the head injury; neurological signs at admission; and neurological outcome. RESULTS: A total of 42 children (median age, 5 years; M/F: 26/16) were treated for head injuries, which involved a slide in 20 cases (47.6%), a swing in 11 (26.2%), a jungle gym in five (11.9%), monkey bars, iron bars, and a trampoline in one each, and unspecified equipment in six (14.3%). Falls ranged from a height of 1.2 to 2.5 m. Most of the falls occurred on hard soil or concrete. Head injuries depended on the age of the child, the injury mechanisms, and the characteristics of the equipment. CONCLUSIONS: The playground equipment-related head injuries found in the present study involved not only skull fractures and concussions, but also intracranial hemorrhage and surgical cases. Children routinely use playground equipment, so effective strategies to reduce the occurrence of playground equipment-related head injuries need to be formulated.

Glue protein production can be triggered by steroid hormone signaling independent of the developmental program in Drosophila melanogaster.

Steroid hormones regulate life stage transitions, allowing animals to appropriately follow a developmental timeline. During insect development, the steroid hormone ecdysone is synthesized and released in a regulated manner by the prothoracic gland (PG) and then hydroxylated to the active molting hormone, 20-hydroxyecdysone (20E), in peripheral tissues. We manipulated ecdysteroid titers, through temporally controlled over-expression of the ecdysteroid-inactivating enzyme, CYP18A1, in the PG using the GeneSwitch-GAL4 system in the fruit fly Drosophila melanogaster. We monitored expression of a 20E-inducible glue protein gene, Salivary gland secretion 3 (Sgs3), using a Sgs3:GFP fusion transgene. In wild type larvae, Sgs3-GFP expression is activated at the midpoint of the third larval instar stage in response to the rising endogenous level of 20E. By first knocking down endogenous 20E levels during larval development and then feeding 20E to these larvae at various stages, we found that Sgs3-GFP expression could be triggered at an inappropriate developmental stage after a certain time lag. This stage-precocious activation of Sgs3 required expression of the Broad-complex, similar to normal Sgs3 developmental regulation, and a small level of nutritional input. We suggest that these studies provide evidence for a tissue-autonomic regulatory system for a metamorphic event independent from the primary 20E driven developmental progression.

Drosophila 4EHP is essential for the larval-pupal transition and required in the prothoracic gland for ecdysone biosynthesis.

Maternal expression of the translational regulator 4EHP (eIF4E-Homologous Protein) has an established role in generating protein gradients essential for specifying the Drosophila embryonic pattern. We generated a null mutation of 4EHP, which revealed for the first time that it is essential for viability and for completion of development. In fact, 4EHP null larvae, and larvae ubiquitously expressing RNAi targeting 4EHP, are developmentally delayed, fail to grow and eventually die. In addition, we found that expressing RNAi that targets 4EHP specifically in the prothoracic gland disrupted ecdysone biosynthesis, causing a block of the transition from the larval to pupal stages. This phenotype can be rescued by dietary administration of ecdysone. Consistent with this, 4EHP is highly expressed in the prothoracic gland and it is required for wild type expression levels of steroidogenic enzymes. Taken together, these results uncover a novel essential function for 4EHP in regulating ecdysone biosynthesis.

Ecdysone differentially regulates metamorphic timing relative to 20-hydroxyecdysone by antagonizing juvenile hormone in Drosophila melanogaster.

In insects, a steroid hormone, 20-hydroxyecdysone (20E), plays important roles in the regulation of developmental transitions by initiating signaling cascades via the ecdysone receptor (EcR). Although 20E has been well characterized as the molting hormone, its precursor ecdysone (E) has been considered to be a relatively inactive compound because it has little or no effect on classic EcR mediated responses. I found that feeding E to wild-type third instar larvae of Drosophila melanogaster accelerates the metamorphic timing, which results in elevation of lethality during metamorphosis and reduced body size, while 20E has only a minor effect. The addition of a juvenile hormone analog (JHA) to E impeded their precocious pupariation and thereby rescued the reduced body size. The ability of JHA impeding the effect of E was not observed in the Methoprene-tolerant (Met) and germ-cell expressed (gce) double mutant animals lacking JH signaling, indicating that antagonistic action of JH against E is transduced via a primary JH receptor, Met, or a product of its homolog, Gce. I also found that L3 larvae are susceptible to E around the time when they reach their minimum viable weight. These results indicate that E, and not just 20E, is also essential for proper regulation of developmental timing and body size. Furthermore, the precocious pupariation triggered by E is impeded by the action of JH to ensure that animals attain body size to survive metamorphosis.

Prediction of thrombolytic therapy after stroke-bypass transportation: the Maria Prehospital Stroke Scale score.

There is no prehospital stratification tool specifically for predicting thrombolytic therapy after transportation. We developed a new prehospital scale named the Maria Prehospital Stroke Scale (MPSS) by modifying the Cincinnati Prehospital Stroke Scale. Our objective is to evaluate its utility in a citywide bypass transportation protocol for intravenous (IV) tissue plasminogen activator (tPA). In the MPSS, facial droop, arm drift, and speech disturbance are tested by emergency medical technicians (EMTs). Facial droop is graded as normal (0) or abnormal (1), and the other 2 items are graded in 3 levels as normal (0), not severe (1), and severe (2). Thus, the total MPSS score ranges from 0 to 5. The predictive value of MPSS for thrombolytic therapy after bypass transportation was evaluated in 1057 patients. The MPSS scored by EMTs was significantly correlated with the National Institutes of Health Stroke Scale score in the emergency room (Spearman rho = .67, P = .000). The onset-to-door time was significantly longer with a low MPSS score (analysis of variance, F5,4.21 = .001). The rate of thrombolytic therapy was increased when the MPSS score increased from 0 to 5: 0%, 4.1%, 8.8%, 13.0%, 20.3%, and 31.5%, respectively. The areas under the receiver operating characteristic curve for the correct diagnosis of stroke and prediction of IV tPA therapy were calculated as .737 (95% confidence interval [CI]: .688-.786) and .689 (95% CI: .645-.732), respectively. Multivariate logistic regression analysis showed that the MPSS score and the detection-to-door time were independent predictors of tPA use after transportation. The MPSS is a novel prehospital stratification tool for the prediction of thrombolytic therapy after transportation.

Redundant actions of neuropeptides encoded by the dh-pban gene for larval color pattern formation in the oriental armyworm Mythimnaseparata.

The pyrokinin (PK)/pheromone biosynthesis-activating neuropeptide (PBAN) family, which is defined by a conserved C-terminal pentapeptide (FXPRLamide), is involved in many physiological processes in insects. In the oriental armyworm Mythimna separata, the larvae exhibit a variety of color patterns in response to changes in population density, which are caused by melanization and a reddish coloration hormone (MRCH), which is a member of the FXPRLamide neuropeptides. Interestingly, in some lepidopteran insects, MRCH is known as a PBAN, which activates the pheromone gland to produce sex pheromones. PBAN is encoded by a single gene, dh-pban, which encodes additional FXPRLamide neuropeptides, such as the diapause hormone (DH) and subesophageal ganglion neuropeptides (SGNPs). To determine the roles of the dh-pban gene, which produces multiple types of FXPRLamide neuropeptides after post-transcriptional cleavage of the precursor protein, we performed CRISPR/Cas9-mediated targeted mutagenesis in M. separata. We demonstrated that knockout armyworm larvae lost density-dependent cuticular melanization and retained yellow body color, even when reared under crowded conditions. Moreover, our rescue experiments using the synthetic peptides showed that not only PBAN but also ß- and γ-SGNPs significantly induce the cuticular melanization in a dose dependent manner. Taken together, our results provide genetic evidence that neuropeptides encoded by the single dh-pban gene act redundantly to control density-dependent color pattern formation in M. separata.

Sentential inference bridging between lexical/grammatical knowledge and text comprehension among native Chinese speakers learning Japanese.

The current study explored the role of sentential inference in connecting lexical/grammatical knowledge and overall text comprehension in foreign language learning. Using structural equation modeling (SEM), causal relationships were examined between four latent variables: lexical knowledge, grammatical knowledge, sentential inference, and text comprehension. The study analyzed 281 Chinese university students learning Japanese as a second language and compared two causal models: (1) the partially-mediated model, which suggests that lexical knowledge, grammatical knowledge, and sentential inference concurrently influence text comprehension, and (2) the wholly-mediated model, which posits that both lexical and grammatical knowledge impact sentential inference, which then further affects text comprehension. The SEM comparison analysis supported the wholly-mediated model, showing sequential causal relationships from lexical knowledge to sentential inference and then to text comprehension, without significant contribution from grammatical knowledge. The results indicate that sentential inference serves as a crucial bridge between lexical knowledge and text comprehension.

Prothoracicotropic hormone regulates developmental timing and body size in Drosophila.

In insects, control of body size is intimately linked to nutritional quality as well as environmental and genetic cues that regulate the timing of developmental transitions. Prothoracicotropic hormone (PTTH) has been proposed to play an essential role in regulating the production and/or release of ecdysone, a steroid hormone that stimulates molting and metamorphosis. In this report, we examine the consequences on Drosophila development of ablating the PTTH-producing neurons. Surprisingly, PTTH production is not essential for molting or metamorphosis. Instead, loss of PTTH results in delayed larval development and eclosion of larger flies with more cells. Prolonged feeding, without changing the rate of growth, causes the overgrowth and is a consequence of low ecdysteroid titers. These results indicate that final body size in insects is determined by a balance between growth-rate regulators such as insulin and developmental timing cues such as PTTH that set the duration of the feeding interval.

Conversion of 3-oxo steroids into ecdysteroids triggers molting and expression of 20E-inducible genes in Drosophila melanogaster.

Ecdysteroids, steroid hormones in insects, coordinate major developmental transitions. During postembryonic development, ecdysone is biosynthesized from dietary cholesterol in the prothoracic gland (PG). Despite extensive studies, the initial conversion process, the so-called "Black Box", has not been characterized. A cytochrome P450 enzyme, Spookier (Spok), is speculated as a rate limiting enzyme in the Black Box during larval-pupal transitions in Drosophila melanogaster. RNAi mediated knockdown of spok expression in the PG results in arrest of molting. Because the developmental arrest can be rescued by application of an appropriate intermediate, we examined potential activities of candidate intermediates in the RNAi-treated larvae. We found that two 3-oxo steroids, cholesta-4,7-diene-3,6-dione-14α-ol (Δ(4)-diketol) and 5ß [H]cholesta-7-ene-3,6-dione-14α-ol (diketol), triggered molting of the RNAi-treated larvae. We also detected an enhancement of the amounts of ecdysteroids in the RNAi-treated larvae by feeding the Δ(4)-diketol or diketol, indicating that the dietary 3-oxo steroids were incorporated and converted into ecdysteroids in vivo. Furthermore, 20-hydroxyecdysone inducible genes were induced in the RNAi-treated larvae by feeding the Δ(4)-diketol or diketol. These results indicate that Δ(4)-diketol and diketol are components of the ecdysteroid biosynthetic pathway and lie downstream of a step catalyzed by Spok.

Functional characterization of an olfactory receptor in the Oriental fruit fly, Bactrocera dorsalis, that responds to eugenol and isoeugenol.

Most insects utilize a diverse array of olfactory cues for host finding and reproduction behaviors. Males of several Dacini fruit fly species (Tephritidae) are selectively attracted to certain phytochemicals to acquire sex pheromone precursors. Despite the importance of olfaction, only a limited number of olfactory receptors (ORs) in Dacini fruit flies have been characterized. In this study, I focused on the OR94b-2 subfamily, because a clade consisting of these homologs was distinctly localized from other OR clades in a constructed phylogenetic tree. To deorphanize the ORs, I used plant essential oils to screen ligands. Using heterologous expression in Xenopus oocytes, I analyzed the functional properties of BdorOR94b-2 and ZcucOR94b-2 from the Oriental fruit fly, Bactrocera dorsalis, and the melon fruit fly, Zeugodacus cucurbitae, respectively. I found that cinnamon leaf oil evoked responses in oocytes expressing BdorOR94b-2 and the corresponding co-receptor BdorORCO. Gas chromatography-mass spectrometry analysis indicated that eugenol is a major component of cinnamon leaf oil. In accordance with the response to cinnamon leaf oil containing eugenol, BdorOR94b-2/BdorORCO revealed a weak but significant response to eugenol. BdorOR94b-2/BdorORCO also responded to isoeugenol, but not to other related aromatic semiochemicals such as known male-specific attractants and sex pheromones. In contrast, ZcucOR94b-2/ZcucORCO did not respond to any of the phenolic compounds tested, including eugenol analogs. Therefore, BdorOR94b-2/BdorORCO is narrowly tuned to eugenol analogs, whereas ZcucOR94b-2/ZcucORCO likely binds to other compound(s).

Oviposition stimulants underlying different preferences between host races in the leaf-mining moth Acrocercops transecta (Lepidoptera: Gracillariidae).

The importance of plant chemistry in the host specialization of phytophagous insects has been emphasized. However, only a few chemicals associated with host shifting have been characterized. Herein, we focus on the leaf-mining moth Acrocercops transecta (Gracillariidae) consisting of ancestral Juglans (Juglandaceae)- and derived Lyonia (Ericaceae)-associated host races. The females of the Lyonia race laid eggs on a cover glass treated with an L. ovalifolia leaf extract; the extract was fractionated using silica gel and ODS column chromatography to isolate the oviposition stimulants. From a separated fraction, two analogous Lyonia-specific triterpenoid glycosides were characterized as oviposition stimulants. Furthermore, we observed probable contact chemosensilla on the distal portion of the female antennae. Lyonia race females laid their eggs on the non-host Juglans after the leaves were treated with a Lyonia-specific oviposition stimulant, although they do not lay eggs on Juglans. These results suggest that Lyonia race females do not lay eggs on Juglans leaves because the leaves do not contain specific oviposition stimulant(s). Otherwise, the activity of the oviposition stimulants overcomes oviposition deterrents contained in Juglans leaves. This paper describes the roles of plant chemicals in the different preferences between host races associated with distantly related plant taxa.

A Case Report of Contrast-Induced Encephalopathy after Repeated Percutaneous Transluminal Angioplasty for Acute Middle Cerebral Artery Occlusion.

Objective: We report a case of contrast-induced encephalopathy (CIE) after repeated percutaneous transluminal angioplasty (PTA) for acute middle cerebral artery (MCA) occlusion. Case Presentation: An 88-year-old woman with left hemiparesis was transferred to our hospital by ambulance. MRI revealed acute MCA M1 occlusion. We performed intravenous tissue plasminogen activator therapy and PTA for right MCA occlusion, leading to complete recanalization and improvement in hemiparalysis. After approximately one week, restenosis of right MCA developed and PTA was performed again on day 11. However, her left hemiparesis exacerbated shortly thereafter. CT demonstrated leakage of contrast medium, and an extensive high-intensity area (HIA) on the white matter in the right cerebral hemisphere was noted on MRI FLAIR. The HIA on MRI and neurological deficits gradually improved after conservative treatment, but diffuse atrophy of the right cerebral hemisphere occurred and higher brain dysfunction remained. Conclusion: Repeated ischemia and reperfusion, and the frequent use of contrast media were considered the causes of CIE.

Recent Advancements in Studies on Chemosensory Mechanisms Underlying Detection of Semiochemicals in Dacini Fruit Flies of Economic Importance (Diptera: Tephritidae).

Dacini fruit flies mainly contain two genera, Bactrocera and Zeugodacus, and include many important pests of fruits and vegetables. Their life cycle is affected by various environmental cues. Among them, multiple characteristic semiochemicals have remarkable effects on their reproductive and host-finding behaviors. Notably, floral fragrances released from so-called fruit fly orchids strongly attract males of several Dacini fruit fly species. Focusing on the strong attraction of male flies to particular chemicals, natural and synthetic lures have been used for pest management. Thus, the perception of semiochemicals is important to understand environmental adaptation in Dacini fruit flies. Since next-generation sequencers are available, a large number of chemosensory-related genes have been identified in Dacini fruit flies, as well as other insects. Furthermore, recent studies have succeeded in the functional analyses of olfactory receptors in response to semiochemicals. Thus, characterization of molecular components required for chemoreception is under way. However, the mechanisms underlying chemoreception remain largely unknown. This paper reviews recent findings on peripheral mechanisms in the perception of odors in Dacini fruit flies, describing related studies in other dipteran species, mainly the model insect Drosophilamelanogaster. Based on the review, important themes for future research have also been discussed.

Evaluation of antixenosis in soybean against Spodoptera litura by dual-choice assay aided by a statistical analysis model: Discovery of a novel antixenosis in Peking.

The method for evaluating soybean (Glycine max) antixenosis against the common cutworm (Spodoptera litura) was developed based on a dual-choice assay aided by a statistical analysis model. This model was constructed from the results of a dual-choice assay in which Enrei, a soybean cultivar susceptible to S. litura, was used as both a standard and a test leaf disc for 2nd-5th instar larvae. The statistical criterion created by this model enabled the evaluation of the presence of antixenosis. This method was applied to four soybean varieties, including Tamahomare (susceptible), Himeshirazu (resistant), IAC100 (resistant), and Peking (unknown), as well as Enrei. Subsequently, the degrees of antixenosis were also compared by F-test, followed by maximum likelihood estimation (MLE). According to the results, the antixenosis of Tamahomare, Himeshirazu, and IAC100 was statistically reevaluated and Peking exhibited a novel antixenosis, which was stronger for 3rd-5th instar larvae than for 2nd instar.

The plant-derived triterpenoid, cucurbitacin B, but not cucurbitacin E, inhibits the developmental transition associated with ecdysone biosynthesis in Drosophila melanogaster.

In insects, some sterols are essential not only for cell membrane homeostasis, but for biosynthesis of the steroid hormone ecdysone. Dietary sterols are required for insect development because insects cannot synthesize sterols de novo. Therefore, sterol-like compounds that can compete with essential sterols are good candidates for insect growth regulators. In this study, we investigated the effects of the plant-derived triterpenoids, cucurbitacin B and E (CucB and CucE) on the development of the fruit fly, Drosophila melanogaster. To reduce the effects of supply with an excess of sterols contained in food, we reared D. melanogaster larvae on low sterol food (LSF) with or without cucurbitacins. Most larvae raised on LSF without supplementation or with CucE died at the second or third larval instar (L2 or L3) stages, whereas CucB-administered larvae mostly died without molting. The developmental arrest caused by CucB was partially rescued by ecdysone supplementation. Furthermore, we examined the effects of CucB on larval-prepupal transition by transferring larvae from LSF supplemented with cholesterol to that with CucB just after the L2/L3 molt. L3 larvae raised on LSF with CucB failed to pupariate, with a remarkable developmental delay. Ecdysone supplementation rescued the developmental delay but did not rescue the pupariation defect. Furthermore, we cultured the steroidogenic organ, the prothoracic gland (PG) of the silkworm Bombyx mori, with or without cucurbitacin. Ecdysone production in the PG was reduced by incubation with CucB, but not with CucE. These results suggest that CucB acts not only as an antagonist of the ecdysone receptor as previously reported, but also acts as an inhibitor of ecdysone biosynthesis.

A Case of Acute Ischemic Stroke Treated with Endovascular Treatment for Tandem Occlusion of the Common Carotid Artery and Internal Carotid Artery Terminal Portion Related to Takayasu Arteritis.

Objective: This report presents a case of mechanical thrombectomy for left internal carotid artery (ICA) terminal portion occlusion performed by left common carotid artery recanalization during hospitalization after diagnosing bilateral common carotid artery occlusion due to Takayasu arteritis. Case Presentation: A 25-year-old woman with fever and cervix pain a few months ago visited our department after repeated transient aphasic attacks. Magnetic resonance imaging (MRI) demonstrated diffuse infarction in the left middle cerebral artery (MCA) area, and she was diagnosed with Takayasu arteritis due to bilateral common carotid artery occlusion and left subclavian artery stenosis. On the 20th day of hospitalization, the terminal portion of the left ICA was occluded and thrombectomy was performed after balloon dilation of the left common carotid artery. Lastly, left common carotid artery stenting was performed. Aphasia and sensory disturbance remained, but she was transferred to a rehabilitation hospital with a modified Rankin Scale (mRS) of 2 on the 65th day of hospitalization. Antithrombotic and immunosuppressive therapy were performed, and restenosis did not develop. Conclusion: Angioplasty and stenting of common carotid artery occlusion can be effective treatments in thrombectomy for intracranial occlusion due to Takayasu disease.