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A new shape of the mixer in supercritical hydrothermal flow-type reactors was proposed and evaluated by neutron radiography and nanoparticle synthesis.

The fruitless gene of Drosophila produces multiple protein isoforms, which are classified into two major classes, sex-specific Fru proteins (FruM) and non-sex specific proteins (FruCOM). Whereas FruM proteins are expressed in ∼2000 neurons to masculinize their structure and function, little is known about FruCOM's roles. As an attempt to obtain clues to the roles of FruCOM, we compared expression patterns of FruCOM and FruM in the central nervous system at the late larval stage. We found that nearly all neuroblasts express FruCOM but not FruM, whereas a subset of ganglion mother cells and differentiated neurons express FruM but not FruCOM. It is inferred that FruCOM proteins support fundamental stem cell functions, contrasting to FruM proteins, which play major roles in sex-specific differentiation of neurons.

While epigamic traits likely evolve via sexual selection, the mechanism whereby internal sexual dimorphism arises remains less well understood. Seeking clues as to how the internal sexual dimorphism evolved, we compared the abdominal musculature of 41 Drosophila montium group species, to determine whether any of these species carry a male-specific muscle of Lawrence (MOL). Our quantitative analysis revealed that the size of a sexually dimorphic MOL analog found in 19 montium group species varied widely from species to species, suggesting the gradual evolution of this sexually dimorphic neuromuscular trait. We attempted the ancestral state reconstitution for the presence or absence of the neuromuscular sexual dimorphism in the A5 segment; the neuromuscular sexual dimorphism existed in an old ancestor of the montium group, which was lost in some of the most recent common ancestors of derived lineages, and subsequently some species regained it. This loss-and-gain history was not shared by evolutionary changes in the courtship song pattern, even though both traits were commonly regulated by the master regulator male-determinant protein FruM. It is envisaged that different sets of FruM target genes may serve for shaping the song and MOL characteristics, respectively, and, as a consequence, each phenotypic trait underwent a distinct evolutionary path.

It remains an enigma how the nervous system of different animal species produces different behaviors. We studied the neural circuitry for mating behavior inDrosophila subobscura, a species that displays unique courtship actions not shared by other members of the genera including the genetic modelD. melanogaster, in which the core courtship circuitry has been identified. We disrupted theD. subobscura fruitless(fru) gene, a master regulator for the courtship circuitry formation inD. melanogaster, resulting in complete loss of mating behavior. We also generatedfrusoChrimV, which expresses the optogenetic activator Chrimson fused with a fluorescent marker under the nativefrupromoter. Thefru-labeled circuitry inD. subobscuravisualized byfrusoChrimVrevealed differences between females and males, optogenetic activation of which in males induced mating behavior including attempted copulation. These findings provide a substrate for neurogenetic dissection and manipulation of behavior in non-model animals, and will help to elucidate the neural basis for behavioral diversification.SIGNIFICANCE STATEMENTHow did behavioral specificity arise during evolution? Here we attempted to address this question by comparing the parallel genetically definable neural circuits controlling the courtship behavior ofDrosophila melanogaster, a genetic model, and its relative,D. subobscura, which exhibits a courtship behavioral pattern unique to it, including nuptial gift transfer. We found that thesubobscura fruitlesscircuit, which is required for male courtship behavior, was slightly but clearly different from itsmelanogastercounterpart, and that optogenetic activation of this circuit inducedsubobscura-specific behavior, i.e., regurgitating crop contents, a key element of transfer of nuptial gift. Our study will pave the way for determining how and which distinctive cellular elements within thefruitlesscircuit determine the species-specific differences in courtship behavior.

The fruitless (fru) locus was originally defined by a male sterile mutation that promotes male‐to‐male courtship while suppressing male‐to‐female courtship in Drosophila melanogaster. The fru promoter‐1 pre‐RNA generates a set of BTB‐zinc finger family FruM proteins expressed exclusively in the male neurons, leading to the formation of sexual dimorphisms in neurons via male‐specific neuroblast proliferation, male‐specific neural survival, male‐specific neuritegenesis or male‐specific arbor patterning. Such a wide spectrum of phenotypic effects seems to result from chromatin modifications, in which FruBM recruits Bonus, Histone deacetylase 1 (HDAC1) and/or Heterochromatin protein 1a (HP1a) to ~130 target sites. One established FruBM transcriptional target is the axon guidance protein gene robo1. Multiple transcriptional regulator‐binding sites are nested around the FruBM‐binding site, and mediate sophisticated modulation of the repressor activity of FruBM. FruBM also binds to the Lola‐Q transcriptional repressor to protect it from proteasome‐dependent degradation in male but not female neurons as FruBM exists only in male neurons, leading to the formation of sexually dimorphic neural structures. These findings shed light on the multilayered network of transcription regulation orchestrated by the master regulator FruBM., Drosophila Fruitless regulates proteolysis to produce sex‐specific Lola isoforms that specify neuronal sex types.

Some mAL neurons in the male brain form the ipsilateral neurite (ILN[+]) in a manner dependent on FruBM, a male-specific transcription factor. FruBM represses robo1 transcription, allowing the ILN to form. We found that the proportion of ILN[+]-mALs in all observed single cell clones dropped from ∼90% to ∼30% by changing the heat-shock timing for clone induction from 4-5 days after egg laying (AEL) to 6-7 days AEL, suggesting that the ILN[+]-mALs are produced predominantly by young neuroblasts. Upon EcR-A knockdown, ILN[+]-mALs were produced at a high rate (∼60%), even when heat shocked at 6-7 days AEL, yet EcR-B1 knockdown reduced the proportion of ILN[+]-mALs to ∼30%. Immunoprecipitation assays in S2 cells demonstrated that EcR-A and EcR-B1 form a complex with FruBM. robo1 reporter transcription was repressed by FruBM and ecdysone counteracted FruBM. We suggest that ecdysone signaling modulates the FruBM action to produce an appropriate number of male-type neurons., Summary: The insect molting hormone ecdysone determines whether a single neuron develops a sex-specific structure, through crosstalk with signaling elements in a pathway dedicated to the sex-fate determination.

In fruit flies, the male-specific fruitless (fru) gene product FruBM plays a central role in establishing the neural circuitry for male courtship behavior by orchestrating the transcription of genes required for the male-type specification of individual neurons. We herein identify the core promoter recognition factor gene Trf2 as a dominant modifier of fru actions. Trf2 knockdown in the sexually dimorphic mAL neurons leads to the loss of a male-specific neurite and a reduction in male courtship vigor. TRF2 forms a repressor complex with FruBM, strongly enhancing the repressor activity of FruBM at the promoter region of the robo1 gene, whose function is required for inhibiting the male-specific neurite formation. In females that lack FruBM, TRF2 stimulates robo1 transcription. Our results suggest that TRF2 switches its own role from an activator to a repressor of transcription upon binding to FruBM, thereby enabling the ipsilateral neurite formation only in males., fruitless (fru) is an important sex-determinant gene that controls the expression of neuroanatomical sex differences in Drosophila. Here the authors report that a core-promoter factor, TRF2, suppresses a male-type neurite specification through direct interaction with FruBM isoform at the robo1 target gene promoter.

It remains an enigma how the nervous system of different animal species produces different behaviors. We studied the neural circuitry for mating behavior in Drosophila subobscura, a species that displays unique courtship actions not shared by other members of the genera including the genetic model D. melanogaster, in which the core courtship circuitry has been identified. We disrupted the D. subobscura fruitless (fru) gene, a master regulator for the courtship circuitry formation in D. melanogaster, resulting in complete loss of mating behavior. We also generated fru(soChrimV), which expresses the optogenetic activator Chrimson fused with a fluorescent marker under the native fru promoter. The fru-labeled circuitry in D. subobscura visualized by fru(soChrimV) revealed differences between females and males, optogenetic activation of which in males induced mating behavior including attempted copulation. These findings provide a substrate for neurogenetic dissection and manipulation of behavior in non-model animals, and will help to elucidate the neural basis for behavioral diversification. SIGNIFICANCE STATEMENT How did behavioral specificity arise during evolution? Here we attempted to address this question by comparing the parallel genetically definable neural circuits controlling the courtship behavior of Drosophila melanogaster, a genetic model, and its relative, D. subobscura, which exhibits a courtship behavioral pattern unique to it, including nuptial gift transfer. We found that the subobscura fruitless circuit, which is required for male courtship behavior, was slightly but clearly different from its melanogaster counterpart, and that optogenetic activation of this circuit induced subobscura-specific behavior, i.e., regurgitating crop contents, a key element of transfer of nuptial gift. Our study will pave the way for determining how and which distinctive cellular elements within the fruitless circuit determine the species-specific differences in courtship behavior.

Neurogenetic analyses in the fruit fly Drosophila melanogaster revealed that gendered behaviors, including courtship, are underpinned by sexually dimorphic neural circuitries, whose development is directed in a sex-specific manner by transcription factor genes, fruitless (fru) and doublesex (dsx), two core members composing the sex-determination cascade. Via chromatin modification the Fru proteins translated specifically in the male nervous system lead the fru-expressing neurons to take on the male fate, as manifested by their male-specific survival or male-specific neurite formations. One such male-specific neuron group, P1, was shown to be activated when the male taps the female abdomen. Moreover, when artificially activated, P1 neurons are sufficient to induce the entire repertoire of the male courtship ritual. These studies provide a conceptual framework for understanding how the genetic code for innate behavior can be embodied in the neuronal substrate.

Silicon oxide thin film was formed using reaction of spin-coated dimethyl-silicone-oil and 5% ozone gas at low temperature of 300°C. Silicone oil is used for lubrication, insulation, and so on, and it is inexpensive and easy to deal with owing to its stability. FT-IR spectrum of the formed silicon oxide film was similar to that of the thermally oxidized film, and we hardly observed peaks of Si-CH3and C-H bonds originated in silicone oil. The Si-OH bonds in the film were observed. The Si-OH bond causes the degradation of the electric properties of the insulator. In order to remove the Si-OH bonds, the silicon oxide film was treated with an argon excimer light at room temperature. The wavelength of the light was 126 nm. The amount of Si-OH bond was drastically reduced by the UV annealing. The energy of the UV light is high and the value is 9.8 eV. The high energy light may cut the bond of Si-OH. Therefore, the amount of Si-OH bond could be reduced.

Temperature characteristic analysis of the triple-junction solar cell was carried out using circuit simulator under concentration conditions. The temperature exponent of saturation current density for each single-junction solar cell was derived. Extracted temperature exponents were used in the equivalent circuit model for the triple-junction solar cell, and the calculations of solar cell performance were carried out at various temperatures and concentration ratios. The calculation results agreed well with the measured results.

When installing concentrator photovoltaic (CPV) systems in desert areas, we must consider the impact of sandstorms on the Fresnel lens in CPV modules. CPV systems are much more sensitive to sandstorms than flat-panel PV systems because they can only use the direct beam component of sunlight. In this study, the transmittance of a PMMA substrate after sandblasting was evaluated and the influence of sandblasting on the output of a CPV system was assessed. The transmittance of PMMA decreased with an increase in the momentum of blown sand. The conversion efficiency of a CPV module was determined by equivalent circuit calculation. The conversion efficiency decreased with increasing momentum. The coefficient of degradation was 0.17 point per unit momentum.

SiC was prepared from Shirasu volcanic ash using solar furnace. The solar furnace is composed by two parts; Fresnel lens and reacting furnace. Fresnel lens is used to concentrate sunlight onto the reacting furnace where the sample was put on. The sample was made from the mixture of SiO2 formed using Shirasu volcanic ash and graphite, and placed in the carbon crucible inside the reacting furnace. By using light of sun concentrated with Fresnel lens, the sample was irradiated for 15 minutes and the furnace was left until it cooled down to room temperature. Both irradiated and cooling processes were done under Ar atmosphere. After the experiment, the sample was evaluated by XRD and Raman spectroscopy and the result indicated that β-SiC was formed.

High purity nanoporous silica was fabricated using Shirasu a volcanic ash as a starting material. The starting materials were melted at 1400°C. A mother glass was formed by quenching the melt in pure water. Leaching was performed by immersing the mother glass into an HCl solution. Nonsilica phases formed by phase separation in the mother glass were leached out with acid solution. The obtained porous silica was more than 99% pure and had pore size smaller than 2 nm. In order to control the pore size, post heat treatment was performed. The treatment temperature was varied from 540 to 600°C for 12 h. The treatment time was varied from 6 to 12 hours at 600°C. The pore size was controlled from 3.1 to 23.4 nm with changing temperature and time for the post heat treatment.

High purity nanoporous silica was fabricated using Shirasu volcanic ash as a starting material. The starting materials were placed into a platinum crucible and were melted at 1400°C. A mother glass was formed by quenching the melt in pure water. Leaching was performed by immersing the mother glass into an HCl solution. Nonsilica phases formed by phase separation in the mother glass were leached out with acid solution. The obtained porous silica was more than 99% pure and had pore size smaller than 2 nm. In order to control the pore size, post heat treatment was performed. The pore size could be controlled from 3.1 to 21.7 nm by changing the post treatment temperature.

The Temperature-Sensitive-Gel (TSG) is a stimulus-responsive gel whose volume and physical properties change responsive to a temperature. The purpose of this research is to develop a novel temperature-responsive microporous film by adding TSG particles into a polymer composite. The TSG particles were synthesized firstly, which have a melting point of around 60 ° C, a spherical shape with the diameter of from 50 to 300 μm. Then the synthesized TSG particles were blended with linear low density polyethylene/calcium carbonate (LLDPE/CaCO3) composite to prepare microporous TSG/LLDPE/CaCO3 film. In this paper, we discuss the processing and physical properties of TSG/LLDPE/CaCO3 composite film. Our findings confirmed the thermal expansion and shrinkage of TSG in the vicinity of its melting temperature. This behavior enables pores close/open, to provide the TSG/LLDPE/CaCO3 composite film temperature-responsive pore-size-adjustment function to control the gas permeability.

Drosophila platonic (plt) males court females, but fail to copulate. Here we show that plt is an allele of scribbler (sbb), a BMP signalling component. sbb knockdown in larvae leads to the loss of approximately eight serotonergic neurons, which express the sex-determinant protein Doublesex (Dsx). Genetic deprivation of serotonin (5-HT) from dsx-expressing neurons results in copulation defects. Thus, sbb+ is developmentally required for the survival of a specific subset of dsx-expressing neurons, which support the normal execution of copulation in adults by providing 5-HT. Our study highlights the conserved involvement of serotonergic neurons in the control of copulatory mechanisms and the key role of BMP signalling in the formation of a sex-specific circuitry., Drosophila platonic (plt) mutant males court with females but fail to copulate. Here, the authors find plt is an allele of scribbler and may disrupt courtship behaviour via developmental disruption of a subgroup of serotonergic Doublesex+ neurons in the abdominal ganglion.

Pattern formation along the proximal-distal (PD) axis in the developing limb bud serves as a good model for learning how cell fate and regionalization of domains, which are essential processes in morphogenesis during development,are specified by positional information. In the present study, detailed fate maps for the limb bud of the chick embryo were constructed in order to gain insights into how cell fate for future structures along the PD axis is specified and subdivided. Our fate map revealed that there is a large overlap between the prospective autopod and zeugopod in the distal limb bud at an early stage (stage 19), whereas a limb bud at this stage has already regionalized the proximal compartments for the prospective stylopod and zeugopod. A clearer boundary of cell fate specifying the prospective autopod and zeugopod could be seen at stage 23, but cell mixing was still detectable inside the prospective autopod region at this stage. Detailed analysis of HOXA11 AND HOXA13 expression at single cell resolution suggested that the cell mixing is not due to separation of some different cell populations existing in a mosaic. Our findings suggest that a mixable unregionalized cell population is maintained in the distal area of the limb bud, while the proximal region starts to be regionalized at the early stage of limb development.

In the pupal stage, the fly body undergoes extensive metamorphic remodeling, in which programmed cell death plays a critical role. We studied two of the constituent processes in this remodeling, salivary gland degeneration and breakdown of the eclosion muscle, which are triggered by an increase and a decrease in the circulating steroid hormone ecdysone at the start and end of metamorphosis, respectively. We found that knockdown of zeste (z), a gene encoding a sequence-specific DNA-binding protein implicated in transvection, in salivary gland cells advances the initiation of their degeneration, whereas z knockdown in neurons delays muscle breakdown. We further showed that knockdown of an ecdysone-inducible gene, E74, retards salivary gland degeneration with little effect on eclosion muscle breakdown. We propose that Z tunes the sensitivity of ecdysone targets to this hormone in order to ensure a high safety margin so that the cell death program will be activated when the ecdysone titer is at a sufficiently high level that is reached only at a defined stage during metamorphosis.

セントラルコア病 (central core disease: CCD) を合併した小児の肝芽腫に対する拡大肝右葉切除術の麻酔を経験した. CCDは近年同定された悪性高熱症 (malignant hyperthermia: MH) の遺伝子と同一の遺伝子異常で発症する先天性非進行性ミオパチーで, CCDの合併は麻酔中にMHを発症する可能性の高い危険因子と考えられている. 当症例ではMHに関する術前評価は十分であったため, とくに問題となることはなかったが, 術中予期せぬ大量出血に遭遇し管理に難渋した.

The muscle of Lawrence (MOL) is a male-specific muscle present in the abdomen of some adult Drosophila species. Formation of the MOL depends on innervation by motoneurons that express fruitless, a neural male determinant. Drosophila melanogaster males carry a pair of MOLs in the 5th abdominal segment, whereas D. subobscura males carry a pair in both the 5th and 4th segments. We hypothesized that the fru gene of D. subobscura but not that of D. melanogaster contains a cis element that directs the formation of the additional pair of MOLs. Successively extended 5' DNA fragments to the P1 promoter of D. subobscura or the corresponding fragments that are chimeric (i.e., containing both melanogaster and subobscura elements) were introduced into D. melanogaster and tested for their ability to induce the MOL to locate the hypothetical cis element. We found that a 1.5-2-kb genomic fragment located 4-6-kb upstream of the P1 promoter in D. subobscura but not that of D. melanogaster permits MOL formation in females, provided this fragment is grafted to the distal ∼4-kb segment from D. melanogaster, demonstrating that this genomic fragment of D. subobscura contains a cis element for the MOL induction.

Two transcription factor genes, fruitless (fru) and doublesex (dsx), are the primary factors that direct the development of brain sex differences in Drosophila. In the nervous system, the dsx gene produces different proteins, DsxM and DsxF, respectively, in males and females, whereas the fru gene produces proteins (FruM) only in males. Thus, the dsx-dependent sex differences in the nervous system likely reflect the distinct target specificity of DsxM and DsxF, whereas the fru-dependent sex differences rely on the presence and absence of FruM. Some neurons express both fru and dsx and others express either fru or dsx, while the majority of neurons express neither. By studying the sexual dimorphism of single neurons, insights into the molecular mechanism whereby FruM specifies the neuronal sex have been obtained. The sexually dimorphic morphologies of a fru-expressing neural cluster in males are completely feminized when FruM is lost, whereas the same cluster has an intersexual appearance under moderate reductions in FruM in fru hypomorphic mutants. Single-cell labeling demonstrates that even in such fru hypomorphic mutants, each neuron in the cluster has a complete male-type structure or a complete female-type structure, indicating that the intersexual appearance of the cluster results from the mixed presence of the male-type and female-type neurons. This all-or-none mode of sex-type determination by FruM is mediated by a competitive recruitment to the FruM-target genomic sites of two antagonistic chromatin regulators, histone deacetylase 1 and heterochromatin protein 1a, each of which masculinizes or demasculinizes single neurons in concert with FruM. These findings open up a new avenue for the study of epigenetic bases for sexual differentiation.

Recently mated Drosophila females were shown to be reluctant to copulate and to exhibit rejecting behavior when courted by a male. Males that experience mate refusal by a mated female subsequently attenuate their courtship effort toward not only mated females but also virgin females. This courtship suppression persists for more than a day, and thus represents long-term memory. The courtship long-term memory has been shown to be impaired in heterozygotes as well as homozygotes of mutants in orb2, a locus encoding a set of CPEB RNA-binding proteins. We show that the impaired courtship long-term memory in orb2-mutant heterozygotes is restored by reducing the activity of lig, another putative RNA-binding protein gene, yet on its own the loss-of-function lig mutation is without effect. We further show that Lig forms a complex with Orb2. We infer that a reduction in the Lig levels compensates the Orb2 deficiency by mitigating the negative feedback for Orb2 expression and thereby alleviating defects in long-term memory.

Purpose Protein C is a vitamin K-dependent anticoagulant and homozygous protein C deficiency is a rare fatal thrombotic disease. This report describes the perioperative management of homozygous protein C deficiency in a patient who underwent a total of three surgical procedures under general anesthesia and the successful use of activated protein C concentrate.

Two transcription factor genes, fruitless (fru) and doublesex (dsx), are the primary factors that direct the development of brain sex differences in Drosophila. In the nervous system, the dsx gene produces different proteins, DsxM and DsxF, respectively, in males and females, whereas the fru gene produces proteins (FruM) only in males. Thus, the dsx-dependent sex differences in the nervous system likely reflect the distinct target specificity of DsxM and DsxF, whereas the fru-dependent sex differences rely on the presence and absence of FruM. Some neurons express both fru and dsx and others express either fru or dsx, while the majority of neurons express neither. By studying the sexual dimorphism of single neurons, insights into the molecular mechanism whereby FruM specifies the neuronal sex have been obtained. The sexually dimorphic morphologies of a fru-expressing neural cluster in males are completely feminized when FruM is lost, whereas the same cluster has an intersexual appearance under moderate reductions in FruM in fru hypomorphic mutants. Single-cell labeling demonstrates that even in such fru hypomorphic mutants, each neuron in the cluster has a complete male-type structure or a complete female-type structure, indicating that the intersexual appearance of the cluster results from the mixed presence of the male-type and female-type neurons. This all-or-none mode of sex-type determination by FruM is mediated by a competitive recruitment to the FruM-target genomic sites of two antagonistic chromatin regulators, histone deacetylase 1 and heterochromatin protein 1a, each of which masculinizes or demasculinizes single neurons in concert with FruM. These findings open up a new avenue for the study of epigenetic bases for sexual differentiation.

Background Adenosine triphosphate (ATP)-sensitive potassium (k+ATP) channels play an important role in pulmonary vasoregulation. However, the effects of volatile anesthetics on k+ATP channel-mediated pulmonary vasoregulation have not been elucidated. The purpose of the present study was to investigate the effects of halothane and enflurane anesthesia on the pulmonary vasodilator response to the selective k+ATP channel agonist lemakalim (BRJ38227) compared with that measured in the conscious state. The authors also investigated the extent to which endogenous neurohumoral vasoconstrictor mechanisms modulate the vasodilator response to k+ATP channel activation. Method Nineteen conditioned, male mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relationship. LPQ plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during gradula (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. After preconstriction with the thromboxane analog, U46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha), the pulmonary vascular dose-response relationship for the k+ATP agonist lemakalim was assessed in the conscious and halothane-anesthetized states and also in the conscious and enflurane-anesthetized states. This protocol was repeated in conscious and halothane-anesthetized dogs after combined neurohumoral block with antagonists of sympathetic alpha 1 adrenoreceptors, arginine vasopressin V1-receptors, and angiotensin II receptors. The effect of the k+ATP antagonist glybenclamide on the baseline LPQ relationship and on the lemakalim dose-response relationship also was assessed in conscious dogs. Results Compared with the conscious state, halothane, enflurane and glybenclamide had no net effect on the baseline LPQ relationship. In contrast, halothane and enflurane attenuated (P < 0.05) the pulmonary vasodilator response to lemakalim compared with the conscious state. Glybenclamide also caused a rightward shift (P < 0.05) in the lemakalim dose-response relationship. Combined neurohumoral block did not modulate the vasodilator response to lemakalim in the conscious state. The halothane-induced attenuation of the vasodilator response to lemakalim was apparent after combined neurohumoral block. Conclusion These results indicate that halothane and enflurane act to reduce the magnitude of K+ATP channel-mediated pulmonary vasodilation. Reflex pulmonary vasoconstriction resulting from K+ATP mediated systematic hypotension does not alter the magnitude of the pulmonary vasodilator response to lemakalim nor is it responsible for the attenuated response to K+ATP channel activation during halothane anesthesia.

Sex differences in the nervous system are prevalent throughout the animal kingdom. In humans, the corpus callosum and anterior commissure are larger in females, whereas some hypothalamic nuclei and associated structures are larger in males. Numerous studies in rodents have demonstrated that when these nuclei are exposed to circulating androgens during the critical period around birth, they develop into male-typical structures. In addition to this organizational effect, androgens exert an activational effect during adulthood. For example, sexually dimorphic gene expression in the hypothalamus and amygdala depends on circulating androgen levels. Cckar encodes a G protein-coupled receptor and its expression is sexually dimorphic. The major of Cckar-expressing neurons in the ventrolateral division of ventromedial hypothalamus (VMHvl) also express progesterone receptor (PR), with a female-biased expansion of arborizations in the anteroventral periventricular hypothalamic nucleus. Selective ablation of these PR-positive neurons in the VMHvl results in a marked reduction in female sexual receptivity and male aggression, demonstrating that these sexually dimorphic neurons contribute to gendered behavior in mammals. Remarkable sex differences in single neurons have been documented in the fruitfly (Drosophila melanogaster). The fruitless (fru) gene in the fruitfly is considered as a major regulator of male courtship circuitry; a male specific fru-expressing neuron cluster, P1, can initiate male courtship when artificially activated even in the absence of courtship target (e.g., a female). The fru gene encodes a set of putative transcription factors that appear to orchestrate the transcription of ~100 genes by recruiting chromatin regulators, histone deacetylase 1 or heterochromatin protein 1a, to the target sites. These studies have unraveled the causal link among genes, brain sexual dimorphisms and gendered behaviors.

In Drosophila melanogaster, the fruitless (fru) gene encoding BTB-Zn-finger transcription factors organizes male sexual behavior by controlling the development of sexually dimorphic neuronal circuitry. However, the molecular mechanism by which fru controls the sexual fate of neurons has been unknown. Our recent study represents a first step toward clarification of this mechanism. We have shown that: (1) Fru forms a complex with the transcriptional cofactor Bonus (Bon), which recruits either of two chromatin regulators, Histone deacetylase 1 (HDAC1) or Heterochromatin protein 1a (HP1a), to Fru-target sites; (2) the Fru-Bon complex has a masculinizing effect on single sexually-dimorphic neurons when it recruits HDAC1, whereas it has a demasculinizing effect when it recruits HP1a; (3) HDAC1 or HP1a thus recruited to Fru-target sites determines the sexual fate of single neurons in an all-or-none manner, as manipulations of HDAC1 or HP1a expression levels affect the proportion of male-typical neurons and female-typical neurons without producing neurons of intersexual characteristics. Here, we hypothesize that chromatin landscape changes induced by ecdysone surges direct the HDAC1- or HP1a-containing Fru complex to distinct targets, thereby allowing them to switch the neuronal sexual fate in the brain.

SummaryThe Drosophila fruitless (fru) gene encodes a set of putative transcription factors that promote male sexual behavior by controlling the development of sexually dimorphic neuronal circuitry. However, the mechanism whereby fru establishes the sexual fate of neurons remains enigmatic. Here, we show that Fru forms a complex with the transcriptional cofactor Bonus (Bon), which, in turn, recruits either of two chromatin regulators, Histone deacetylase 1 (HDAC1), which masculinizes individual sexually dimorphic neurons, or Heterochromatin protein 1a (HP1a), which demasculinizes them. Manipulations of HDAC1 or HP1a expression change the proportion of male-typical neurons and female-typical neurons rather than producing neurons with intersexual characteristics, indicating that on a single neuron level, this sexual switch operates in an all-or-none manner.

The vertebrate hand plate is flattened and paddle shaped; that is, it is wide along the anteroposterior (AP) axis (thumb to little finger) and thin along the dorsoventral axis (back of hand to palm). To learn how the hand plate develops its three-dimensional architecture, we observed morphological changes in the distal limb bud of the chick embryo at stages 23-27 and the gecko embryo 11-13 days after oviposition. Cell population of the posterior distal limb bud expanded more than that of the anterior one in the chick embryo. Taken together with the observation that these two cell populations did not show significant differences in their expansion along the proximodistal axis, we propose that the cell population in the posterior limb bud contributes more to the morphogenetic increase along the AP axis, which widens the limb bud for the formation of the hand plate. Our observation that more mitoses were oriented anteroposteriorly than dorsoventrally in the chick embryo at around stage 25 suggests that the oriented cell division contributes to the morphogenetic increase along the AP axis.

Background: Pediatric anesthesia in Japan is in the developing stage. The aim of this study was to review pediatric anesthesia training in Japan and to discuss the future prospects for this field. Methods: We sent questionnaires to assess current pediatric anesthetic practice and training to all 106 university hospitals [UHs; response rate, 66% (70/106)] and all 17 children's hospitals [CHs; response rate, 87.5% (15/17)] in Japan. We also sent questionnaires to assess attitudes towards pediatric anesthetic training, to all 280 representatives of the Japanese Society of Anesthesiologists [JSA; response rate, 57.9% (162/280)]. Results: The hospital survey revealed the number of pediatric anesthesia cases encountered in 15 CHs (25 009 cases) to be almost equivalent to that in 70 UHs (29 031 cases). In 19 of these UHs, there were no newborn surgical cases. Forty-nine UHs reported that no special training program existed for pediatric anesthesia, and only five UHs mandated training at CHs. Sixty-six percent of the representative JSA members considered it premature for pediatric anesthesia to become a subspecialty, but 87% considered experience in pediatric anesthesia mandatory for anesthesia board qualification. Conclusions: This survey revealed that although pediatric anesthesia training is considered mandatory, university hospitals lack adequate numbers of pediatric cases and children's hospitals suffer from a shortage of staff positions and anesthesiologists, and hence are unable to satisfy this demand. Most representative members of our society consider it too early to subspecialize pediatric anesthesia in Japan.

Background The authors previously reported that the pulmonary vasodilator response to the sympathetic beta-adrenoreceptor agonist isoproterenol is potentiated during isoflurane anesthesia compared with the conscious state. In the present in vivo study, the authors tested the hypothesis that halothane and enflurane anesthesia also enhance sympathetic beta adrenoreceptor-mediated pulmonary vasodilation. The authors also used the membrane-permeable analog of cyclic adenosine monophosphate (cAMP), dibutyryl cAMP, to help delineate the site in the signaling pathway for an anesthesia-induced effect on beta adrenoreceptor-mediated pulmonary vasodilation. Methods Mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relationship. LPQ plots were measured on separate days in the conscious, halothane-, and enflurane-anesthetized states at baseline, after preconstriction with the thromboxane analog U46619, and during the cumulative intravenous administration of isoproterenol. LPQ plots were also measured in conscious, halothane-, and isoflurane-anesthetized dogs after U46619 preconstriction and during the cumulative intravenous administration of dibutyryl cAMP. Results Compared with the conscious state, neither halothane nor enflurane had an effect on the baseline LPQ relationship. The magnitude of the pulmonary vasodilator response to isoproterenol was potentiated during halothane anesthesia but unchanged during enflurane anesthesia. The pulmonary vasodilator response to dibutyryl cAMP was not altered during either halothane or isoflurane anesthesia compared with the conscious state. Conclusions These results indicate that inhalational anesthetic agents can exert differential effects on the pulmonary vasodilator response to sympathetic beta-adrenoreceptor activation. The potentiated vasodilator response observed during halothane and isoflurane anesthesia is the result of effects proximal to cAMP accumulation in the beta-adrenoreceptor signaling pathway.

Hypothermic retrograde cerebral perfusion is a new technique for protecting the brain. Satisfactory cerebral protection should be possible even for periods of retrograde perfusion greater than 60 minutes. However, there are some concerns that functioning venous valves at the jugular-subclavian junction may impede retrograde flow to the brain and consequently cerebral protection may not be adequate. To overcome this obstacle, we have developed an easy and safe technique of selective jugular cannulation through the right atrium using a central venous catheter and a guidewire. We have employed this technique successfully in 15 patients who underwent operation on the aortic arch.

2,2,2-trifluoroethanol (CF 3 CH 2 OH) has found an increasing number of drug, chemical and engineering applications. It has been generally produced by reduction of trifluoroacetyl chloride (1) or acetolysis of 1,1,1-trifluro -2-chloroethane followed by hydrolysis of 1,1,1-trifluoroethylacetate (2). The authors investigated the process (2), especially, the effect of solvents on the acetolysis of CF 3 CH 2 CI. The reaction between CF 3 CH 2 Cl and alkaline acetate was carried out in the presence of various solvents in the autoclave. Both the protic and aprotic solvents ware examined. When the protic solvent such as water or ethylene glycol was used, although the CF 3 CH 2 OH could be directly prepared, the reaction rate was low and resulted in low yield of product and moreover corrosive acetic acid which would damage the reaction vessel was simultaneously produced. On the other hand, when the polar aprotic solvent was employed, the reaction rate increased and high yield of esterification was attained, particularly, sulfolane, N-methyl-2-pyrrolidone and N,N-dimethylacetamide gave good result. The mechanism of esterification in these polar aprotic solvents will be also discussed.