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1.
Zoolog Sci ; 38(5): 416-426, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34664916

RESUMO

Although many animals that perform sexual reproduction exhibit sexual dimorphism, individuals with intersex traits between the traits of males and females appear in some species, depending on environmental factors. Ptychognathus ishii, a varunid crab, exhibits distinctive sexual dimorphism in the morphology of its abdomen, chelipeds and setal tufts on the chelipeds. In this study, however, we report for the first time that intersex individuals with intermediate characters between those of males and females were occasionally found in wild populations. Morphological features of intersex individuals are described. Their taxonomic positions are identified based on DNA sequences of part of the mitochondrial cytochrome c oxidase I (COI) gene. It was shown that the intersexuality was induced by entoniscid parasites, because all intersex individuals were parasitized by entoniscid isopods, identified as Entionella sp. The apparent correlation between parasitism and morphological anomalies suggests that the parasitic isopods affect physiological conditions, leading to the feminization of male hosts.


Assuntos
Braquiúros/parasitologia , Transtornos do Desenvolvimento Sexual/parasitologia , Caracteres Sexuais , Animais , Braquiúros/anatomia & histologia , Braquiúros/genética , Feminino , Isópodes/classificação , Masculino , Análise de Sequência de DNA
2.
Anal Chem ; 93(36): 12162-12169, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34473490

RESUMO

The goal of the qNMR Summit is to take stock of the status quo and the recent developments in qNMR research and applications in a timely and accurate manner. It provides a platform for both advanced and novice qNMR practitioners to receive a well-rounded update and discuss potential qNMR-related applications and collaborations. For over a decade, scientists from academia, industry, nonprofit institutions, and governmental bodies have focused on the standardization of qNMR methodology, as well as its metrological and pharmacopeial utility. This paper reviews key content of qNMR Summits 1.0 to 4.0 and puts into perspective the outcomes and available transcripts of the October 2019 Summit 5.0, with attendees from the United States, Canada, Japan, Korea, and several European countries. Summit presentations focused on qNMR methodology in the pharmaceutical industry, advanced quantitation algorithms, and promising developments.


Assuntos
Tecnologia , Canadá , Japão , Padrões de Referência , Estados Unidos
3.
Zoolog Sci ; 38(3): 203-212, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34057344

RESUMO

In bryozoans (phylum Bryozoa), representative colonial animals mostly found in marine environments, some species possess different types of individuals (heterozooids) specialized in different functions such as defense or structural support for their colonies. Among them, the best-known heterozooids are the avicularia, known to function as defenders. The differentiation processes of heterozooids, including avicularia, should be important keys to understand the evolutionary significance of bryozoans. However, the developmental process of avicularium formation remains to be fully understood. In this study, therefore, in order to understand the detailed developmental process and timing of avicularium formation, extensive observations were carried out in a bryozoan species, Bugulina californica (Cheilostomata, Bugulidae), that possesses adventitious avicularia, by performing stereomicroscopy on live materials, in addition to scanning electron microscopy and histological observations. The whole process can be divided into seven stages based on developmental events. Especially notably, at the earlier stages, there are three major budding events that produce proliferating cell masses corresponding to primordial tissues: (1) budding of the peduncle cushion at the outer margin of the distal part of a young autozooid, (2) budding of the head-part primordium from the peduncle cushion, and (3) budding of the polypide inside the head part. Experimental control of temperature showed that 20°C would be the best to maintain B. californica colonies.


Assuntos
Briozoários/crescimento & desenvolvimento , Animais , Evolução Biológica , Briozoários/genética , Briozoários/ultraestrutura , Microscopia Eletrônica de Varredura
4.
Chem Pharm Bull (Tokyo) ; 69(7): 630-638, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33853973

RESUMO

Recently, quantitative NMR (qNMR), especially 1H-qNMR, has been widely used to determine the absolute quantitative value of organic molecules. We previously reported an optimal and reproducible sample preparation method for 1H-qNMR. In the present study, we focused on a 31P-qNMR absolute determination method. An organophosphorus compound, cyclophosphamide hydrate (CP), listed in the Japanese Pharmacopeia 17th edition was selected as the target compound, and the 31P-qNMR and 1H-qNMR results were compared under three conditions with potassium dihydrogen phosphate (KH2PO4) or O-phosphorylethanolamine (PEA) as the reference standard for 31P-qNMR and sodium 4,4-dimethyl-4-silapentanesulfonate-d6 (DSS-d6) as the standard for 1H-qNMR. Condition 1: separate sample containing CP and KH2PO4 for 31P-qNMR or CP and DSS-d6 for 1H-qNMR. Condition 2: mixed sample containing CP, DSS-d6, and KH2PO4. Condition 3: mixed sample containing CP, DSS-d6, and PEA. As conditions 1 and 3 provided good results, validation studies at multiple laboratories were further conducted. The purities of CP determined under condition 1 by 1H-qNMR at 11 laboratories and 31P-qNMR at 10 laboratories were 99.76 ± 0.43 and 99.75 ± 0.53%, respectively, and those determined under condition 3 at five laboratories were 99.66 ± 0.08 and 99.61 ± 0.53%, respectively. These data suggested that the CP purities determined by 31P-qNMR are in good agreement with those determined by the established 1H-qNMR method. Since the 31P-qNMR signals are less complicated than the 1H-qNMR signals, 31P-qNMR would be useful for the absolute quantification of compounds that do not have a simple and separate 1H-qNMR signal, such as a singlet or doublet, although further investigation with other compounds is needed.


Assuntos
Ciclofosfamida/análise , Água/análise , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fósforo
5.
Chem Pharm Bull (Tokyo) ; 69(1): 26-31, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390518

RESUMO

As a new absolute quantitation method for low-molecular compounds, quantitative NMR (qNMR) has emerged. In the Japanese Pharmacopoeia (JP), 15 compounds evaluated by qNMR are listed as reagents used as the HPLC reference standards in the assay of crude drug section of the JP. In a previous study, we revealed that humidity affects purity values of hygroscopic reagents and that (i) humidity control before and during weighing is important for a reproducible preparation and (ii) indication of the absolute amount (not purity value), which is not affected by water content, is important for hygroscopic products determined by qNMR. In this study, typical and optimal conditions that affect the determination of the purity of ginsenoside Rb1 (GRB1), saikosaponin a (SSA), and barbaloin (BB) (i.e., hygroscopic reagents) by qNMR were examined. First, the effect of humidity before and during weighing on the purity of commercial GRB1, with a purity value determined by qNMR, was examined. The results showed the importance afore-mentioned. The results of SSA, which is relatively unstable in the dissolved state, suggested that the standardization of humidity control before and during weighing for a specific time provides a practical approach for hygroscopic products. In regard to BB, its humidity control for a specific time, only before weighing, is enough for a reproducible purity determination.


Assuntos
Antracenos/análise , Ginsenosídeos/análise , Higroscópicos/análise , Ácido Oleanólico/análogos & derivados , Saponinas/análise , Antracenos/normas , Ginsenosídeos/normas , Umidade , Higroscópicos/normas , Japão , Espectroscopia de Ressonância Magnética/normas , Ácido Oleanólico/análise , Ácido Oleanólico/normas , Saponinas/normas
6.
Chem Pharm Bull (Tokyo) ; 69(1): 118-123, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33087642

RESUMO

Quantitative NMR (qNMR) is applied to determine the absolute quantitative value of analytical standards for HPLC-based quantification. We have previously reported the optimal and reproducible sample preparation method for qNMR of hygroscopic reagents, such as saikosaponin a, which is used as an analytical standard in the assay of crude drug section of Japanese Pharmacopoeia (JP). In this study, we examined the absolute purity determination of a hygroscopic substance, indocyanine green (ICG), listed in the Japanese Pharmaceutical Codex 2002, using qNMR for standardization by focusing on the adaptation of ICG to JP. The purity of ICG, as an official non-Pharmacopoeial reference standard (non-PRS), had high variation (86.12 ± 2.70%) when preparing qNMR samples under non-controlled humidity (a conventional method). Additionally, residual ethanol (0.26 ± 0.11%) was observed in the non-PRS ICG. Next, the purity of non-PRS ICG was determined via qNMR when preparing samples under controlled humidity using a saturated sodium bromide solution. The purity was 84.19 ± 0.47% with a lower variation than that under non-controlled humidity. Moreover, ethanol signal almost disappeared. We estimated that residual ethanol in non-PRS ICG was replaced with water under controlled humidity. Subsequently, qNMR analysis was performed when preparing samples under controlled humidity in a constant temperature and humidity box. It showed excellent results with the lowest variation (82.26 ± 0.19%). As the use of a constant temperature and humidity box resulted in the lowest variability, it is recommended to use the control box if the reference ICG standard is needed for JP assays.


Assuntos
Verde de Indocianina/análise , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Molhabilidade
7.
J Morphol ; 282(2): 205-216, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33159480

RESUMO

Basket stars, that is, Ophiuroidea in Echinodermata, exhibit distinctive morphological characteristics with their complicatedly branched arms that can regenerate immediately after mutilation. Although, in brittle stars, that is, ophiuroids with nonbranched arms, the arm regeneration process following accidental trauma or autotomy have been morphologically and histologically observed in several species, few studies have so far been carried out on the regeneration of branched arms in basket stars. In this study, the developmental and morphological features of arm regeneration in Astrocladus dofleini (Gorgonocephalidae, Euryalida, Euryophiurida), one of the most common basket star species in Japanese waters, was anatomically and histologically investigated. Results clearly showed the following phases during the arm regeneration: (a) repair phase, (b) early regenerative phase, (c) intermediate regenerative phase, (d) advanced regenerative Phase I, and (e) advanced regenerative Phase II. The morphogenetic process during the arm regeneration in the basket star showed similar patterns to those of nonbranched arms observed in other ophiuroids. However, differences were also seen between the two ophiuroid types, that is, there were some developmental features specific to the basket star. In the early regenerative phase, branching of coelomic cavities was observed prior to the formation of other tissues, probably inducing the later morphogenesis of branched arms. In addition, hard skeletal ossicles form rapidly at the advanced regenerative Phase II. These developmental features may have led the evolution of bizarre morphologies seen in basket stars, probably contributing to the adaptation to shallow waters from deep-sea habitats.


Assuntos
Equinodermos/anatomia & histologia , Equinodermos/fisiologia , Morfogênese , Animais , Equinodermos/citologia , Sistema Musculoesquelético/anatomia & histologia , Regeneração
8.
Zoolog Sci ; 37(6): 563-574, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33269872

RESUMO

Amphibians exhibit phenotypic plasticity, which allows flexible adaptation to fluctuating environments. Although genes involved in expression of plastic phenotypes have been identified, the endocrine bases of plastic responses are largely unknown. Larvae of the Hokkaido salamander (Hynobius retardatus) plastically display distinct phenotypes, an "offensive phenotype" characterized as larger body with broadened gape and a "defensive phenotype" characterized as enlarged gills and tail and less active behavior, in the presence of prey larval amphibians and predatory larval dragonfly, respectively. In the presence of both prey and predators, the degree of induction of both phenotypes is reduced, suggesting cross-talk between the molecular signaling pathways of these phenotypes. We conducted a transcriptomic analysis to examine how endocrine regulation affects the phenotypic expression by focusing on the pituitary gland. We found that five endocrine genes, i.e., calcitonin related polypeptide alpha (CALCA), growth hormone (GH), neuropeptide B (NPB), parathyroid hormone 2 (PTH2), and prolactin 1 (PRL1), were involved in the expression of both phenotypes. However, we conducted only RNA-seq analysis, and no confirmation of significant up-regulation or down-regulation has been conducted. These results suggest that these genes were up-regulated for induction of the offensive phenotype and down-regulated for induction of the defensive phenotype. Phylogenetic analysis indicated that possible gene duplications of PRL and CALCA have occurred during amphibian evolution. Based on these findings, it is suggested that a trade-off of molecular signaling pathways exists between the two distinct phenotypic expressions. The results also suggest that hormonal-gene duplications might have contributed to the acquisition of phenotypic plasticity in amphibians.


Assuntos
Adaptação Fisiológica/genética , Comportamento Predatório , Urodelos/genética , Animais , Perfilação da Expressão Gênica , Larva/genética , Larva/metabolismo , Odonatos , Filogenia , Hipófise/fisiologia , Hormônios Hipofisários/genética , Hormônios Hipofisários/metabolismo , Ranidae , Urodelos/crescimento & desenvolvimento , Urodelos/metabolismo
9.
Sci Rep ; 10(1): 18566, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-33122746

RESUMO

Caenorhabditis elegans (C. elegans) exhibits cold tolerance and temperature acclimatisation regulated by a small number of head sensory neurons, such as the ADL temperature-sensing neurons that express three transient receptor potential vanilloid (TRPV) channel subunits, OSM-9, OCR-2, and OCR-1. Here, we show that an OSM-9/OCR-2 regulates temperature acclimatisation and acts as an accessorial warmth-sensing receptor in ADL neurons. Caenorhabditis elegans TRPV channel mutants showed abnormal temperature acclimatisation. Ectopic expression of OSM-9 and OCR-2 in non-warming-responsive gustatory neurons in C. elegans and Xenopus oocytes revealed that OSM-9 and OCR-2 cooperatively responded to warming; however, neither TRPV subunit alone was responsive to warming. A warming-induced OSM-9/OCR-2-mediated current was detectable in Xenopus oocytes, yet ADL in osm-9 ocr-2 double mutant responds to warming; therefore, an OSM-9/OCR-2 TRPV channel and as yet unidentified temperature receptor might coordinate transmission of temperature signalling in ADL temperature-sensing neurons. This study demonstrates direct sensation of warming by TRPV channels in C. elegans.


Assuntos
Aclimatação/genética , Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Proteínas do Tecido Nervoso/genética , Canais de Cátion TRPV/genética , Animais , Mutação/genética , Oócitos/fisiologia , Sensação/genética , Células Receptoras Sensoriais/fisiologia , Transdução de Sinais/genética , Temperatura , Xenopus/genética
10.
Yakugaku Zasshi ; 140(8): 1063-1069, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32741864

RESUMO

Quantitative NMR (qNMR) has been developed as an absolute quantitation method to determine the purity or content of organic compounds including marker compounds in crude drugs. The "qNMR test" has been introduced into the crude-drug section of the Japanese Pharmacopoeia (JP) for determining the purity of reagents used for the assay in the JP. In Supplement II to the JP 17th edition published in June 2019, fifteen compounds adopted qNMR test were listed as the reagents for the assay. To establish the "qNMR test" in the crude drug section of the JP, there were several problems to be solved. Previously, we reported that the handling impurity signals from reference substances and targeted marker compounds, chemical shifts of reference substances, and peak unity of signals of targeted marker compounds are important factors to conduct qNMR measurements with intended accuracy. In this study, we investigated that the hygroscopicity of reagents could cause the changes in the compounds' purity depending on increasing their water content. Twenty-one standard products used for the crude-drug test in JP were examined by water sorption-desorption analysis, and ginsenosides and saikosaponins were found to be hygroscopic. To prepare a sample solution of saikosaponin b2 for qNMR analysis, samples need to be maintained for 18 h at 25°C and 76% relative humidity; further, samples need to be weighed at the same humidity for the qNMR analysis.


Assuntos
Contaminação de Medicamentos/prevenção & controle , Higroscópicos/química , Higroscópicos/normas , Indicadores e Reagentes/normas , Espectroscopia de Ressonância Magnética/métodos , Farmacopeias como Assunto/normas , Ginsenosídeos/química , Ginsenosídeos/normas , Umidade , Japão , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/normas , Psicoterapia Breve , Saponinas/química , Saponinas/normas , Temperatura , Água/análise
11.
Front Zool ; 17: 24, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32855651

RESUMO

Background: Morphological novelties have been acquired through evolutionary processes and related to the adaptation of new life-history strategies with new functions of the bodyparts. Cephalopod molluscs such as octopuses, squids and cuttlefishes possess unique morphological characteristics. Among those novel morphologies, in particular, suckers arranged along the oral side of each arm possess multiple functions, such as capturing prey and locomotion, so that the sucker morphology is diversified among species, depending on their ecological niche. However, the detailed developmental process of sucker formation has remained unclear, although it is known that new suckers are formed or added during both embryonic and postembryonic development. In the present study, therefore, focusing on two cuttlefish species, Sepia esculenta and S. lycidas, in which the sucker morphology is relatively simple, morphological and histological observations were carried out during embryonic and postembryonic development to elucidate the developmental process of sucker formation and to compare them among other cephalopod species. Results: The observations in both species clearly showed that the newly formed suckers were added on the oral side of the most distal tip of each arm during embryonic and postembryonic development. On the oral side of the arm tip, the epithelial tissue became swollen to form a ridge along the proximal-distal axis (sucker field ridge). Next to the sucker field ridge, there were small dome-shaped bulges that are presumed to be the sucker buds. Toward the proximal direction, the buds became functional suckers, in which the inner tissues differentiated to form the complex sucker structures. During postembryonic development, on both sides of the sucker field ridge, epithelial tissues extended to form a sheath, covering the ridge for protection of undifferentiated suckers. Conclusions: The developmental process of sucker formation, in which sucker buds are generated from a ridge structure (sucker field ridge) on the oral side at the distal-most arm tip, was shared in both cuttlefish species, although some minor heterochronic shifts of the developmental events were detected between the two species.(325 words).

12.
Chem Pharm Bull (Tokyo) ; 68(9): 868-878, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32565492

RESUMO

NMR spectroscopy has recently been utilized to determine the absolute amounts of organic molecules with metrological traceability since signal intensity is directly proportional to the number of each nucleus in a molecule. The NMR methodology that uses hydrogen nucleus (1H) to quantify chemicals is called quantitative 1H-NMR (1H qNMR). The quantitative method using 1H qNMR for determining the purity or content of chemicals has been adopted into some compendial guidelines and official standards. However, there are still few reports in the literature regarding validation of 1H qNMR methodology. Here, we coordinated an international collaborative study to validate a 1H qNMR based on the use of an internal calibration methodology. Thirteen laboratories participated in this study, and the purities of three samples were individually measured using 1H qNMR method. The three samples were all certified via conventional primary methods of measurement, such as butyl p-hydroxybenzoate Japanese Pharmacopeia (JP) reference standard certified by mass balance; benzoic acid certified reference material (CRM) certified by coulometric titration; fludioxonil CRM certified by a combination of freezing point depression method and 1H qNMR. For each sample, 1H qNMR experiments were optimized before quantitative analysis. The results showed that the measured values of each sample were equivalent to the corresponding reference labeled value. Furthermore, assessment of these 1H qNMR data using the normalized error, En-value, concluded that statistically 1H qNMR has the competence to obtain the same quantification performance and accuracy as the conventional primary methods of measurement.


Assuntos
Espectroscopia de Ressonância Magnética/normas , Ácido Benzoico/química , Calibragem , Dioxóis/química , Hidroxibenzoatos/química , Cooperação Internacional , Espectroscopia de Ressonância Magnética/métodos , Pirróis/química , Padrões de Referência , Reprodutibilidade dos Testes
13.
Sci Rep ; 10(1): 9435, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32523105

RESUMO

Eusocial insects exhibit reproductive division of labor, in which only a fraction of colony members differentiate into reproductives. In termites, reproductives of both sexes are present in a colony and constantly engaged in reproduction. It has been suggested that the sex ratio of reproductives is maintained by social interactions. The presence of reproductives is known to inhibit the additional differentiation of same-sex reproductives, while it promotes the differentiation of opposite-sex reproductives. In this study, using the damp-wood termite Hodotermopsis sjostedti, physiological effects of male/female reproductives on the differentiation of supplementary reproductives (neotenics) were examined. The results showed that the only male-neotenic condition, i.e., the presence of male neotenics in the absence of female neotenics, accelerated the neotenic differentiation from female workers (i.e., pseudergates). Under this condition, the rise of juvenile hormone (JH) titer was repressed in females, and the application of a JH analog inhibited the female neotenic differentiation, indicating that the low JH titer leads to rapid differentiation. Thus, the only male-neotenic condition that actively promotes reproductive differentiation by manipulating physiological condition of females is suggested to be a mechanism underlying sexual asymmetry in reproductive function, which may lead the female-biased sex allocation of reproductives.


Assuntos
Isópteros/fisiologia , Reprodução/fisiologia , Diferenciação Sexual/fisiologia , Animais , Diferenciação Celular/genética , Feminino , Isópteros/metabolismo , Hormônios Juvenis/metabolismo , Hormônios Juvenis/fisiologia , Masculino , Reprodução/genética , Sexo , Diferenciação Sexual/genética
14.
Micromachines (Basel) ; 11(6)2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32580457

RESUMO

As a supramolecular micromachine with information flow, a giant vesicle (GV)-based artificial cell that exhibits a linked proliferation between GV reproduction and internal DNA amplification has been explored in this study. The linked proliferation is controlled by a complex consisting of GV membrane-intruded DNA with acidic amphiphilic catalysts, working overall as a lipo-deoxyribozyme. Here, we investigated how a GV-based artificial cell containing this lipo-deoxyribozyme responds to diverse external and internal environments, changing its proliferative dynamics. We observed morphological changes (phenotypic expression) in GVs induced by the addition of membrane precursors with different intervals of addition (starvation periods). First, we focused on a new phenotype, the "multiple tubulated" form, which emerged after a long starvation period. Compared to other forms, the multiple tubulated form is characterized by a larger membrane surface with a heavily cationic charge. A second consideration is the effect of the chain length of encapsulated DNA on competitive proliferation. The competitive proliferation among three different species of artificial cells containing different lengths of DNA was investigated. The results clearly showed a distinct intervention in the proliferation dynamics of the artificial cells with each other. In this sense, our GV-based artificial cell can be regarded as an intelligent supramolecular machine responding to external and internal environments, providing a new concept for developing molecular machines and robotics.

15.
Evol Dev ; 22(6): 425-437, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32291940

RESUMO

Termites (Blattodea, Termitoidea, or Isoptera) constitute one of the major lineages of eusocial insects. In termite societies, multiple types of functional individuals, that is, castes, perform divisions of labors to coordinate social behaviors. Among other castes, the soldier caste is distinctive since it is sterile and exclusively specialized into defensive behavior with largely modified morphological features. Therefore, many of the previous studies have been focused on soldiers, in terms of ecology, behavior, and evolution as well as developmental and physiological mechanisms. This article overviews the accumulation of studies especially focusing on the developmental and physiological mechanisms underlying the soldier differentiation in termites. Furthermore, the evolutionary trajectories that have led the acquisition of soldier caste and have diversified the soldier characteristics in association with the social evolution are discussed.


Assuntos
Evolução Biológica , Isópteros/fisiologia , Animais , Evolução Molecular , Isópteros/genética , Isópteros/crescimento & desenvolvimento , Comportamento Social
16.
Bioorg Med Chem ; 28(11): 115457, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32334935

RESUMO

We synthesized and identified four metabolites of acyl-coenzyme A:cholesterol O-acyltransferase (ACAT)-1 inhibitor, K-604 (1). Two of the metabolites M1 and M2, were prepared from 1 using a combination reagent of hydrogen peroxide and sodium tungstate with either phosphoric acid or trifluoroethanol as the solvent to control the regioselectivity. Upon exposure of 4b to tert-butyl hypochlorite at -78 °C, the monosulfoxidation afforded synthetic intermediate of M3 in excellent yield. The efficient synthesis of M4 was established. The in vitro metabolic study exhibited a high clearance value (720 µL/min/mg protein) of 1 using human liver microsomes. We orally administered a single dose of 10 mg/kg of 1 to monkeys because the in vitro metabolic patterns are quite similar. Fortunately, the drug concentration of 1 was much higher than those of M1, M2, M3 and M4.


Assuntos
Benzimidazóis/farmacocinética , Esterol O-Aciltransferase/antagonistas & inibidores , Animais , Benzimidazóis/química , Benzimidazóis/metabolismo , Relação Dose-Resposta a Droga , Humanos , Macaca fascicularis , Masculino , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Esterol O-Aciltransferase/metabolismo , Relação Estrutura-Atividade
17.
Insect Biochem Mol Biol ; 111: 103177, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31228516

RESUMO

In the evolutionarily-derived termite subfamily Nasutitermitinae (family Termitidae), soldiers defend their nestmates by discharging polycyclic diterpenes from a head projection called the "nasus." The diterpenes are synthesised in the frontal gland from the precursor geranylgeranyl diphosphate (GGPP), which is generally used for post-translational modification of proteins in animals. In this study, we constructed a comprehensive gene catalogue to search for genes involved in the diterpene biosynthesis by assembling RNA sequencing reads of Nasutitermes takasagoensis, identifying eight gene copies for GGPP synthase (GGPPS). The number of gene copies is much larger in contrast to other related insects. Gene cloning by reverse transcription-PCR and rapid amplification of cDNA ends confirmed that seven GGPPS genes (NtGGPPS1 to NtGGPPS7) have highly variable untranslated regions. Molecular phylogenetic analysis showed that the NtGGPPS7 gene was grouped with homologs obtained from ancestral termites that have only a single copy of the gene, and the NtGGPPS6 gene was grouped with homologs obtained from a basal lineage of termitids, in which soldiers do not synthesise diterpenes. As the sister group to this clade, furthermore, a monophyletic clade included all the other NtGGPPS genes (NtGGPPS1 to NtGGPPS5). Expression analyses revealed that NtGGPPS7 gene was expressed in all the examined castes and tissues, whereas all the other genes were expressed only in the soldier head. These results suggest that gene duplication followed by subfunctionalisation of the GGPPS genes might have accompanied the evolution of chemical defence in the nasute termite lineage.


Assuntos
Farnesiltranstransferase/metabolismo , Proteínas de Insetos/metabolismo , Isópteros/enzimologia , Isópteros/genética , Animais , Farnesiltranstransferase/biossíntese , Farnesiltranstransferase/genética , Regulação Enzimológica da Expressão Gênica , Proteínas de Insetos/biossíntese , Proteínas de Insetos/genética , Filogenia , Análise de Sequência de RNA
18.
Evodevo ; 10: 10, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123582

RESUMO

Background: Generally in termites, alates differentiate through multiple nymphal instars which gradually develop wing buds. However, in a dampwood termite, Hodotermopsis sjostedti, alates molt directly from a single nymphal instar with short wing buds. In this study, to examine the mechanism underlying the wing formation during the alate differentiation in H. sjostedti, histological and morphological observations were carried out on the developmental process of wing formation during the nymphal instar, in comparison with those in Zootermopsis nevadensis, which has two nymphal instars. Furthermore, the expression patterns of genes that are thought to be responsible for wing formation, i.e., wing-patterning genes and genes encoding hormone-related factors, were quantified during alate differentiation and compared between the two species. Results: The results showed that, in H. sjostedti, wings were formed in a complicatedly folded shape, not only inside the wing buds as seen in Z. nevadensis, but also under the dorsal thoracic cuticle, where the wing tips shifted toward the median thoracic part. Accordingly, the wing expansion pattern also differed from that in Z. nevadensis. Furthermore, the results of real-time qRT-PCR on overall expression profiles of wing-patterning genes and hormone-related genes suggest that the single nymphal instar in H. sjostedti well resembles to the second nymphal instar in Z. nevadensis. In particular, significant upregulation of vestigial (vg) and downregulation of Krüppel homolog 1 (Kr-h1) that were observed at the second nymphal instar in Z. nevadensis apparently occurred during the single nymphal instar in H. sjostedti. Conclusion: The developmental events for wing formation are compacted into a single nymphal instar in H. sjostedti, and as a result, the unique wing formation is seen to compensate for the spatial restriction inside small wing buds, leading to the completion of functional wings.

19.
Development ; 146(5)2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833380

RESUMO

In social insects, interactions among colony members trigger caste differentiation with morphological modifications. In termite soldier differentiation, the mandible size considerably increases through two moltings (via the presoldier stage) under the control of juvenile hormone (JH). Regulatory genes are predicted to provide patterning information that induces the mandible-specific cell proliferation. To identify factors responsible for the mandibular enlargement, expression analyses of 18 candidate genes were carried out in the termite Hodotermopsis sjostedti Among those, dachshund (dac), which identifies the intermediate domain along the proximodistal appendage axis, showed mandible-specific upregulation prior to the molt into presoldiers, which can explain the pattern of cell proliferation for the mandibular elongation. Knockdown of dac by RNAi reduced the mandibular length and distorted its morphology. Furthermore, the epistatic relationships among Methoprene tolerant, Insulin receptor, Deformed (Dfd) and dac were revealed by combined RNAi and qRT-PCR analyses, suggesting that dac is regulated by Dfd, downstream of the JH and insulin signaling pathways. Thus, caste-specific morphogenesis is controlled by interactions between the factors that provide spatial information and physiological status.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Proteínas de Insetos/metabolismo , Isópteros/embriologia , Hormônios Juvenis/metabolismo , Mandíbula/embriologia , Proteínas Nucleares/metabolismo , Animais , Comportamento Animal , Padronização Corporal , Epistasia Genética , Perfilação da Expressão Gênica , Genes Homeobox , Insulina/metabolismo , Isópteros/genética , Muda , Morfogênese , Interferência de RNA , Transdução de Sinais
20.
Dev Growth Differ ; 61(1): 85-96, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30467834

RESUMO

Phenotypic plasticity and polyphenism, in which phenotypes can be changed depending on environmental conditions, are common in insects. Several studies focusing on physiological, developmental, and molecular processes underlying the plastic responses have revealed that similar endocrine mechanisms using juvenile hormone (JH) are used to coordinate the flexible developmental processes. This review discusses accumulated knowledge on the caste polyphenism in social insects (especially termites), the wing and the reproductive polyphenisms in aphids, and the nutritional polyphenism and sexual dimorphism in stag beetles. For the comparison with non-insect arthropods, extensive studies on the inducible defense (and reproductive polyphenism) in daphnids (crustacean) are also addressed. In all the cases, JH (and methyl farnesoate in daphnids) plays a central role in mediating environmental stimuli with morphogenetic processes. Since the synthetic pathways for juvenoids, i.e., the mevalonate pathway and downstream pathways to sesquiterpenoids, are conserved across pancrustacean lineages (crustaceans and hexapods including insects), the evolution of developmental regulation by juvenoids that control molting (ecdysis) and metamorphosis is suggested to have occurred in the ancestral arthropods. The discontinuous postembryonic development (i.e., molting) and the regulatory physiological factors (juvenoids) would have enabled plastic developmental systems observed in many arthropod lineages.


Assuntos
Adaptação Fisiológica/fisiologia , Hormônios Juvenis/metabolismo , Fenótipo , Animais , Insetos , Polimorfismo Genético/genética
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